Prostate arterial embolization (PAE) has been investigated as a minimally invasive alternative to transurethral resection of the prostate (TURP), considered the traditional standard treatment for benign prostatic hyperplasia (BPH). PAE differs from other minimally invasive surgical therapies in treatment approach (endovascular vs transurethral) and mechanism (embolic), and thus requires different considerations. An interventional radiologist injects microspheres through a catheter to the blood vessels around the prostate, reducing the blood supply to multiple different areas. No surgical intervention is required for this procedure and recovery times are often less than that of TURP.

Drug-coated balloons (DCBs) deliver antiproliferative agents directly to the coronary vessel wall via a semicompliant balloon coated with drugs (typically paclitaxel, sirolimus, or everolimus) embedded in a carrier matrix that rapidly diffuses into the vessel wall during inflation, without requiring permanent stent implantation. This approach provides localized drug delivery to inhibit neointimal hyperplasia while avoiding additional metallic layers.

Inherited retinal dystrophy can be caused by recessive variants in the RPE65 gene. Individuals with biallelic variants have difficulty seeing in dim light and experience progressive loss of vision. These disorders are rare and have traditionally been considered untreatable. Gene therapy with an adeno-associated virus vector expressing RPE65 has been proposed as a treatment to improve visual function.

Triple S Salud has a procedure designed to ensure the evaluation of requests for coverage of covered medications recommended for orphan drugs, off- labeled and expanded access drugs indications that are prescribed for “medically accepted indications”. Off-label or “unlabeled” drug use is the use of a drug approved by the U.S. Food and Drug Administration (FDA) for other uses that are not included in approved labeling (may be for oncology or non oncology use). The FDA approves drugs for specific indications that are included in the drug’s labeling. When a drug is used for an indication other than those specifically included in the labeling, it is referred to as an off-label use. Many off-label uses are effective, well documented in the literature, and widely used. An “orphan drug” is a product that treats a rare disease (e.g., affecting fewer than 200,000 Americans). Products have FDA orphan drug approval when they meet the orphan drug criteria established by the FDA. The intent of the Orphan Drug Act (ODA) is to stimulate the research, development, and approval of products that treat rare diseases. Orphan designation can be obtained prior to submission of a marketing application. The safety and efficacy of the drug must be established through clinical studies. If the designated product meets the standard FDA regulatory requirements and process for obtaining marketing approval, it is given an FDA approved orphan drug designation status (i.e., “Designated/Approved”). Over 1,400 drugs and biologics have been designated as orphan drugs and over 250 have been approved for marketing. Expanded access refers to the use of an investigational new drug (IND) outside of a clinical trial by patients with serious or life-threatening conditions who do not meet the enrollment criteria for the clinical trial in progress. This type of access may be available, in accordance with United States Food and Drug Administration (FDA) regulations, when it is clear that patients may benefit from the treatment, the therapy can be given safely outside the clinical trial setting, no other alternative therapy is available, and the drug developer agrees to provide access to the drug. The FDA refers to such a program as an expanded access program (EAP). [1] EAPs can be used in a wide range of therapeutic areas including HIV/AIDS and other infectious diseases, cancer, rare diseases, and cardiovascular diseases. There are several types of EAPs allowed in the United States. Treatment protocols and treatment INDs provide large numbers of patients access to investigational drugs. A single-patient IND is a request from a physician to the FDA that an individual patient be allowed access to an investigational drug on an emergency or compassionate use basis. <a id="

Cerebral adrenoleukodystrophy (CALD) is an X-linked genetic neurodegenerative disease that most severely affects individuals assigned male at birth. The genetic mutation leads to impaired or loss of adrenoleukodystrophy protein (ALDP) expression. X-linked adrenoleukodystrophy is established in a male (assigned male at birth or AMAB) with suggestive clinical findings and elevated very long chain fatty acids (VLCFA), with the majority having inherited a pathogenic variant in the ABCD1 gene. While female (assigned female at birth or AFAB) carriers can develop spastic paraparesis most often in adulthood, adrenal function is generally not impaired. CALD typically only affects AMAB in childhood and AFAB with CALD are very rare. Defective function of ALDP leads to the accumulation of very long-chain fatty acids (VLCFAs), which occurs in plasma and all tissue types but most prominently in the adrenal cortex and white matter of the brain and spinal cord. VLCFAs initiate an inflammatory cascade ultimately leading to inflammatory cerebral demyelination. In general, once clinical symptoms appear, the clinical course is rapid with progressive cognitive and neurologic deficits leading to major disability including cortical blindness, incontinence, requirement for tube feeding, loss of communication, loss of ambulation, loss of voluntary movement, and ultimately premature death. Prior to the approval of elivaldogene autotemcel, there were no approved treatments for CALD in the US. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered the standard of care and has been shown to stabilize neurologic function, with better outcomes observed in patients treated at the early stages of cerebral involvement and among those who receive human leukocyte antigen (HLA)-matched transplant versus HLA-mismatched transplant. Challenges associated with HSCT include serious immunologic complications, including transplant-related mortality, graft rejection, and graft-versus-host disease. Elivaldogene autotemcel is an autologous hematopoietic stem cell (HSC)-based gene therapy which adds functional copies of the ABCD1 cDNA into patients’ HSCs through transduction of autologous CD34+ cells with Lenti-D lentiviral vector. After infusion, transduced CD34+ HSCs engraft in the bone marrow and differentiate into various cell types, including monocytes (CD14+) capable of producing functional ALDP. Functional ALDP can then participate in the local degradation of VLCFAs, which is believed to slow or possibly prevent further inflammation and demyelination.

Denosumab is a fully human monoclonal antibody against receptor activator of nuclear factor κ-β ligand (RANKL) and inhibits its action on the surface receptors expressed on osteoclasts. This causes reduced osteoclast formation, function and survival, consequently decreasing bone resorption, increasing bone mass, and strengthening both cortical and trabecular bone. The role of excessive RANKL as a contributor to conditions characterized by bone loss or bone destruction has been well studied. A comprehensive clinical development program for denosumab resulted in a robust data set that supported global and regulatory approvals of the RANKL-targeted antibody denosumab in the bone loss and cancer inducted bone destruction settings. <a id="

Denosumab is a fully human monoclonal antibody against receptor activator of nuclear factor κ-β ligand (RANKL) and inhibits its action on the surface receptors expressed on osteoclasts. This causes reduced osteoclast formation, function and survival, consequently decreasing bone resorption, increasing bone mass, and strengthening both cortical and trabecular bone. The role of excessive RANKL as a contributor to conditions characterized by bone loss or bone destruction has been well studied. A comprehensive clinical development program for denosumab resulted in a robust data set that supported global and regulatory approvals of the RANKL-targeted antibody denosumab in the bone loss and cancer inducted bone destruction settings. <a id="

Tonic motor activation (TOMAC) is a peroneal nerve stimulation device that uses electrodes worn on the lower legs to deliver bilateral high-frequency electrical stimulation to the common peroneal nerves located near the fibula in the lower legs. This stimulation is proposed to activate the tibialis anterior muscle, producing sustained, low-level muscle contractions that mimic the effects of voluntary leg movements like walking or stretching, which are activities known to relieve restless legs syndrome RLS symptoms.

Metabolic dysfunction-associated steatohepatitis (MASH), formerly known as non-alcoholic steatohepatitis (NASH), is a progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD) and a part of the larger spectrum of liver disease. MASH is differentiated from other causes of steatohepatitis by the presence of metabolic dysfunction and exclusion of excessive alcohol intake. The clinical burden of MASH is related not only to the risk of cirrhosis and hepatocellular carcinoma, but also cardiovascular disease, chronic kidney disease, type 2 diabetes, and extrahepatic cancers. Although lifestyle modifications are the primary treatments for MASH, pharmacotherapeutic options are promising. Resmetirom, a liver-directed thyroid hormone receptor beta-selective agonist, was the first agent to receive FDA approval in adults with noncirrhotic MASH and moderate to advanced fibrosis in March 2024. This approval was quickly followed by the approval of semaglutide for the same indication in August 2025.

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare autosomal recessive neurodevelopmental disorder caused by biallelic pathogenic variants in the DDC gene, resulting in reduced or absent activity of the AADC enzyme. This enzyme, expressed in both central and peripheral tissues, catalyzes the conversion of L-DOPA and 5-hydroxytryptophan into the neurotransmitter's dopamine and serotonin, respectively. AADC deficiency leads to impaired synthesis of dopamine, serotonin, norepinephrine, and epinephrine, contributing to a broad spectrum of clinical manifestations. The phenotypic spectrum is heterogenous and reflect deficits in monoaminergic neurotransmission. Phenotype ranges from mild (e.g., mild delay in developmental milestones, ambulatory without assistance, mild intellectual disability) to severe (e.g., no or very limited developmental milestones, fully dependent on caregivers). Approximately 80% of affected individuals present with severe phenotype. Dopamine deficiency primarily contributes to motor symptoms such as hypotonia, dystonia, delayed motor development, and oculogyric crises; norepinephrine and epinephrine deficiencies affect autonomic functions including ptosis, hypoglycemia, and hypotension; serotonin deficiency may impair cognition, voluntary movement, and emotional regulation. Prior to the approval of eladocagene exuparvovec, no FDA-approved therapies were available. Standard of care involved off-label use of oral medications such as dopamine agonists, monoamine oxidase inhibitors, and pyridoxine, though their efficacy and durability remain poorly characterized due to limited case reports. Eladocagene exuparvovec is a recombinant adeno-associated virus serotype 2 based vector gene therapy product containing the complementary DNA of the human DDC gene under the control of the cytomegalovirus immediate-early promoter. It is produced in human embryonic kidney cells by recombinant DNA technology. It is administered in a single stereotactic surgery using a cannula that is FDA-authorized for intraparenchymal infusion.

Azficel-T is an autologous cellular product composed of fibroblasts indicated for improvement of the appearance of moderate to severe nasolabial fold wrinkles in adults. Dermal fibroblasts are collected from the post-auricular biopsy tissue and aseptically expanded using standard tissue-culture procedures until sufficient cells for three doses are obtained. Expanded cells are then suspended in a cell medium. As a replacement for lost dermal constituents in the aging or skin deformation process, treatment with autologous fibroblasts has shown to improve wrinkle and acne scar appearance than with placebo treatment. Intradermal administration of autologous dermal fibroblasts into irradiated skin following surgical procedures was associated with an improved healing process of subsequent surgical wounds. Azficel-T is marketed in the US as Laviv for intradermal injection. <a id="

Mitotic inhibitors (Paclitaxel, Docetaxel, Abraxane) are chemotherapy agents used in multiple solid tumors, including breast, ovarian, lung, prostate, gastric, pancreatic, and Kaposi’s sarcoma. Docetaxel Drug used alone or with other drugs to treat certain types of breast cancer, stomach cancer, gastroesophageal junction cancer, non-small cell lung cancer, prostate cancer, and squamous cell carcinoma of the head and neck. It is also being studied in the treatment of other types of cancer. Docetaxel stops cancer cells from growing and dividing and may kill them. It is a type of taxane. Paclitaxel A drug used alone or with other drugs to treat AIDS-related Kaposi sarcoma, advanced ovarian cancer, and certain types of breast cancer and non-small cell lung cancer. It is also being studied in the treatment of other types of cancer. Paclitaxel stops cancer cells from growing and dividing and may kill them. It is a type of taxane. Abraxene Paclitaxel protein-bound particles are an albumin-bound form of paclitaxel, an antineoplastic agent. Paclitaxel protein-bound particles are indicated for the treatment of breast cancer after the failure of combination chemotherapy for metastatic disease, or relapse within six months of chemotherapy. Recommended therapy is 260 mg/m2 administered via intravenous (IV) infusion over 30 minutes every 3 weeks. Paclitaxel protein-bound particles are contraindicated in patients with baseline neutrophil counts of less than 1,500. A type of drug that blocks cell growth by stopping mitosis (cell division). They are used to treat cancer. Also called antimitotic agent. <a id="

Mitotic inhibitors (Paclitaxel, Docetaxel, Abraxane) are chemotherapy agents used in multiple solid tumors, including breast, ovarian, lung, prostate, gastric, pancreatic, and Kaposi’s sarcoma. Docetaxel Drug used alone or with other drugs to treat certain types of breast cancer, stomach cancer, gastroesophageal junction cancer, non-small cell lung cancer, prostate cancer, and squamous cell carcinoma of the head and neck. It is also being studied in the treatment of other types of cancer. Docetaxel stops cancer cells from growing and dividing and may kill them. It is a type of taxane. Paclitaxel A drug used alone or with other drugs to treat AIDS-related Kaposi sarcoma, advanced ovarian cancer, and certain types of breast cancer and non-small cell lung cancer. It is also being studied in the treatment of other types of cancer. Paclitaxel stops cancer cells from growing and dividing and may kill them. It is a type of taxane. Abraxene Paclitaxel protein-bound particles are an albumin-bound form of paclitaxel, an antineoplastic agent. Paclitaxel protein-bound particles are indicated for the treatment of breast cancer after the failure of combination chemotherapy for metastatic disease, or relapse within six months of chemotherapy. Recommended therapy is 260 mg/m2 administered via intravenous (IV) infusion over 30 minutes every 3 weeks. Paclitaxel protein-bound particles are contraindicated in patients with baseline neutrophil counts of less than 1,500. A type of drug that blocks cell growth by stopping mitosis (cell division). They are used to treat cancer. Also called antimitotic agent. <a id="

An idiopathic facial nerve palsy, or unilateral facial nerve paresis/paralysis, commonly referred to as Bells’s Palsy, is the most common acute mono-neuropathy disorder of unknown origin affecting a single cranial nerve VII, associated with facial nerve weakness or paralysis. Electrostimulation (electrical stimulation) refers to the application of electrical current through electrodes placed directly on the skin. For individuals diagnosed with Bell’s palsy who receive electrotherapy as stimulation to the affected facial muscles, the evidence includes systematic reviews. Relevant outcomes are symptoms, quality of life, and treatment-related morbidity. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Amtagvi (lifileucel) is an autologous TIL (tumor-infiltrating lymphocyte) therapy approved by the FDA in February 2024 for the treatment of unresectable or metastatic melanoma in adults who have failed anti–PD-1 immunotherapy and, if BRAF V600 positive, targeted therapy with BRAF ± MEK inhibitors. The approval is accelerated, and continued approval is contingent upon confirmatory evidence of clinical benefit. <a id="

Aucatzyl is an autologous anti-CD19 CAR-T therapy indicated for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (B-ALL). Recommended total dose: 410 × 10⁶ CAR⁺ T cells, given in 2 split infusions (Day 1 and Day 10 ±2 days) after lymphodepleting chemotherapy. Boxed warnings for CRS (cytokine release syndrome), ICANS (immune effector cell-associated neurotoxicity), and secondary hematologic malignancies. No formal contraindications in the Prescribing Information. <a id="

Encelto (revakinagene taroretcel-lwey) is a cell-based implant designed to continuously deliver recombinant human ciliary neurotrophic factor (rhCNTF) within the retina. It is indicated for the treatment of adult patients with idiopathic macular telangiectasia type 2, non-proliferative, to slow photoreceptor degeneration and preserve visual function.

KEBILIDI is an adeno-associated virus (AAV) vector-based gene therapy 12 indicated for the treatment of adult and pediatric patients with aromatic 13 L-amino acid decarboxylase (AADC) deficiency. <a id="

Lantidra (donislecel-jujn) is an allogeneic pancreatic islet cell therapy approved by the FDA in June 2023. It is indicated for the treatment of adults with type 1 diabetes who are unable to achieve target HbA1c due to recurrent severe hypoglycemia and who have hypoglycemia unawareness despite intensive insulin therapy. It is the first FDA-approved allogeneic islet cell product. Therapy involves one or more infusions of islet cells into the hepatic portal vein, requiring lifelong immunosuppression.

Allogeneic processed thymus tissue–agdc (Rethymic) was approved by the US Food and Drug Administration (FDA) in October 2021 for immune reconstitution in pediatric patients with congenital athymia. It is the first treatment to be approved for this fatal condition. The thymus tissue is obtained from donors less than or equal to 9 months of age undergoing cardiac surgery. The manufacturing process preserves the thymic epithelial cells and tissue structure and depletes most of the donor thymocytes from the tissue. The proposed mechanism of action involves the migration of recipient T cell progenitors from the bone marrow to the implanted thymus tissue, where they develop into naïve immunocompetent recipient T cells. Evidence of thymic function will be observed by the development of naïve T cells in the peripheral blood occurring at least 6 months after treatment. Congenital athymia is an ultra-rare condition in which children are born without a thymus, causing vulnerability to life-threatening infections and immune dysregulation. The estimated incidence of congenital athymia in the US is approximately 17 to 24 infants per 4 million live births annually. The thymus is responsible for the development of mature T cells and is the only organ where thymocytes can mature, be selected, and survive to become naive T cells. T cells originate in the bone marrow as progenitor cells; however, the bone marrow does not contain the specialized tissue required for T-cell maturation. Without a functioning thymus, the inability to produce immunocompetent T cells leads to immunodeficiency manifested as increased susceptibility to infection. With only supportive care, children with congenital athymia typically do not survive beyond 2 to 3 years of age. Congenital athymia is often associated with other conditions, such as DiGeorge syndrome (a.k.a., 22q11.2 deletion syndrome); mutations in the genes TBX1, CHD7 (CHARGE syndrome – coloboma, heart defects, choanal atresia, growth or mental retardation, genital hypoplasia, and ear anomalies and/or deafness), and FOXN1 (FOXN1 deficiency); and diabetic embryopathy. These systemic conditions make the complex treatment of congenital athymia even more complicated. Early detection of congenital athymia is critical, as the sooner it is identified, the sooner isolation, infection prevention measures, and prophylactic antimicrobials can be initiated. Newborn screening plays a crucial role in early detection. <a id="

Remestemcel-L-rknd (Ryoncil) is FDA-approved for the treatment of steroid-refractory acute graftversus-host disease (SR-aGvHD) in pediatric patients greater than or equal to 2 months of age. It contains mesenchymal stromal cells (MSC) from the bone marrow of healthy human adult donors. MSCs inhibit T-cell activation which have a role in the inflammatory response and organ damage associated with acute graft-versus-host disease (aGvHD). <a id="

Gefitinib (Iressa®) is an orally administered tyrosine kinase inhibitor (TKI) of the epidermal growth factor receptor (EGFR). It is FDA-approved for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations, as detected by an FDA-approved test.

Pemetrexed (Alimta) was initially approved by the U.S. Food and Drug Administration (FDA) in February 2004 for use in combination with cisplatin for the treatment of malignant pleural mesothelioma in adults whose disease is unresectable or who are not otherwise candidates for curative surgery. The FDA has since approved pemetrexed as single agent therapy in locally advanced or metastatic non-small cell lung cancer following prior chemotherapy, for use in combination with cisplatin for first-line therapy in locally advanced or metastatic non-squamous non-small cell lung cancer, and for maintenance treatment of advanced or metastatic nonsquamous non-small cell lung cancer after first-line treatment with platinum-based chemotherapy. The agent received orphan drug status from the FDA for the malignant pleural mesothelioma. Pemetrexed acts as a multi-targeted antifolate compound that disrupts folate-dependent metabolic processes that are essential for cell replication. Mutltiple pemetrexed products are available that have been approved via the 505(b)(2) New Drug Application (NDA) process. They have different HCPCS codes are are not considered interchangeable. National Comprehensive Cancer Network (NCCN) Guidelines for Malignant Pleural Mesothelioma (Version 1.2022), Non-Small Cell Lung Cancer (Version 1.2022), Ovarian Cancer (Version 3.2021), Thymomas and Thymic Carcinomas (Version 1.2022), and Central Nervous System Cancers (Version 2.2021) include recommendations for use of pemetrexed. <a id="

Cerebral adrenoleukodystrophy (CALD) is an X-linked genetic neurodegenerative disease that most severely affects individuals assigned male at birth. The genetic mutation leads to impaired or loss of adrenoleukodystrophy protein (ALDP) expression. X-linked adrenoleukodystrophy is established in a male (assigned male at birth or AMAB) with suggestive clinical findings and elevated very long chain fatty acids (VLCFA), with the majority having inherited a pathogenic variant in the ABCD1 gene. While female (assigned female at birth or AFAB) carriers can develop spastic paraparesis most often in adulthood, adrenal function is generally not impaired. CALD typically only affects AMAB in childhood and AFAB with CALD are very rare. Defective function of ALDP leads to the accumulation of very long-chain fatty acids (VLCFAs), which occurs in plasma and all tissue types but most prominently in the adrenal cortex and white matter of the brain and spinal cord. VLCFAs initiate an inflammatory cascade ultimately leading to inflammatory cerebral demyelination. In general, once clinical symptoms appear, the clinical course is rapid with progressive cognitive and neurologic deficits leading to major disability including cortical blindness, incontinence, requirement for tube feeding, loss of communication, loss of ambulation, loss of voluntary movement, and ultimately premature death. Prior to the approval of elivaldogene autotemcel, there were no approved treatments for CALD in the US. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered the standard of care and has been shown to stabilize neurologic function, with better outcomes observed in patients treated at the early stages of cerebral involvement and among those who receive human leukocyte antigen (HLA)-matched transplant versus HLA-mismatched transplant. Challenges associated with HSCT include serious immunologic complications, including transplant-related mortality, graft rejection, and graft-versus-host disease. Elivaldogene autotemcel is an autologous hematopoietic stem cell (HSC)-based gene therapy which adds functional copies of the ABCD1 cDNA into patients’ HSCs through transduction of autologous CD34+ cells with Lenti-D lentiviral vector. After infusion, transduced CD34+ HSCs engraft in the bone marrow and differentiate into various cell types, including monocytes (CD14+) capable of producing functional ALDP. Functional ALDP can then participate in the local degradation of VLCFAs, which is believed to slow or possibly prevent further inflammation and demyelination. <a id="

TECELRA (afamitresgene autoleucel) is a melanoma-associated antigen A4 (MAGEA4)-directed genetically modified autologous T cell immunotherapy product consisting of CD4 and CD8 positive T cells transduced with a self-inactivating lentiviral vector (LV) expressing an affinity-enhanced T cell receptor (TCR) specific for the human MAGE-A4. Autologous T cells transduced with MAGE-A4-c1032 LV express the affinity-enhanced TCR on the cell surface. The TCR recognizes an HLA-A*02 restricted MAGE-A4 peptide. MAGE-A4 is an intracellular cancer-testis antigen that has restricted expression in normal tissues and is expressed in synovial sarcoma. TECELRA was approved by the U.S. Food and Drug Administration (FDA) on August 1, 2024 for the treatment of adults with unresectable or metastatic SyS who have received prior chemotherapy, are HLA-A*02:01P, -A*02:02P, -A*02:03P, or -A*02:06P positive, and whose tumor expresses the MAGE-A4 antigen as determined by FDA-approved or cleared companion diagnostic devices. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Synovial sarcoma (SyS) is a rare, aggressive soft tissue sarcoma that can occur in many parts of the body but most commonly develops in the extremities. Each year, SyS affects about 1000 people in the United States. Treatment of SyS typically involves surgery to remove the tumor and may also include radiotherapy or chemotherapy if the tumor is larger, returns after being removed, or has spread beyond its original location. <a id="

Clinical assessment, routine monitoring, and noninvasive imaging of allograft function after renal transplant can be limited in accurately diagnosing individuals with acute rejection (AR) or other forms of injury because symptoms and signs poorly correlate with objective methods of assessing kidney allograft dysfunction. For management of AR, clinical signs and symptoms (eg, serum creatinine, glomerular filtration rate [GFR], and proteinuria) are relatively crude markers of renal dysfunction and occur late in the course of an exacerbation. Thus, noninvasive urine biomarkers have potential benefit in surveillance and management of renal allograft function. In transplant recipients, despite the progress in immunosuppressant therapy, the risk of rejection still remains. Diagnosis of allograft rejection continues to rely on clinical monitoring and histologic confirmation by tissue biopsy. However, due to limitations of tissue biopsy, including a high degree of interobserver variability in the grading of results and its potential complications, less invasive alternatives have been investigated. A laboratory developed test, One Lambda Laboratories CXCL10 assay, uses a noninvasive urine-based biomarker (CXCL10 protein) to support routine monitoring of graft dysfunction. One Lambda laboratories CXCL10 assay measures the concentration of the CXCL10/IP-10 protein within a urine sample.

Fundus photography Fundus photography is the practice of using a retinal camera to record anomalies in the retina and eye-related disease processes so that the progression of the disease can be tracked. The test must be utilized to make medical decisions for the patient. Extended ophthalmoscopy Extended ophthalmoscopy is a thorough examination of the retina that always includes a true drawing of the retina, interpretation, and report. It is typically conducted using an indirect lens, although it can also be done with contact lens biomicroscopy. This is often done with the pupil dilated and may need scleral depression. It is performed when a more detailed examination is needed, following routine ophthalmoscopy. <a id="

Transcatheter tricuspid valve repair or replacement is an emerging alternative to surgical therapy for patients with severe tricuspid regurgitation (TR), particularly those at elevated surgical risk. TR may result from a primary structural abnormality of the tricuspid valve or, more commonly, from secondary annular dilation and leaflet tethering due to right ventricular remodeling associated with left-sided heart failure, pulmonary hypertension, or atrial fibrillation. Surgical intervention for isolated TR is often underutilized due to high perioperative risk and limited referral, highlighting a substantial unmet need for less invasive treatment options. Two transcatheter devices, TriClip™ (Abbott) and EVOQUE™ (Edwards Lifesciences), have been developed to address this gap. TriClip, a transcatheter edge-to-edge repair system, is designed to reduce TR by approximating valve leaflets, while the EVOQUE system provides a complete transcatheter valve replacement through a self-expanding prosthesis anchored within the native valve structure. Both devices are intended for patients with severe symptomatic TR who are not suitable candidates for surgery and continue to experience symptoms despite optimized medical therapy.

Subacromial balloon spacer implantation represents a minimally invasive treatment modality for massive irreparable rotator cuff tears. The biodegradable spacer is introduced arthroscopically into the subacromial region where it functions to depress the humeral head, successfully reestablishing normal shoulder mechanics by blocking upward displacement of the humeral head toward the acromion. This technique addresses pain and functional limitations by creating a temporary articulating interface between the humeral head and acromion by reducing subacromial impingement. The biodegradable spacer gradually deflates over several months, potentially allowing time for adaptation of surrounding tissues and pain reduction without the complexity of tendon transfers or reverse shoulder arthroplasty.

Approximately 240,000 men in the United States are expected to be diagnosed with prostate cancer in 2016. Although most are diagnosed at an early localized stage, up to 30% of cases will be repeated after surgical therapy or curative radiotherapy. Androgen deprivation therapy, either with surgical or gonadotropin releasing castration analogous to the hormone, is normally initiated to control the disease in people who have developed metastases. Unfortunately, almost all these cases will continue progressing. When patients turn to androgen deprivation therapy in the adjustment of "castration" levels of testosterone, patients receive the name of "castration-resistant". <a id="

Sickle cell retinopathy is a known complication of sickle cell disease. Sickle cell retinopathy is characterized by occlusion of the retinal vasculature resulting in ischemia and infarction of the retina and is classified into nonproliferative and proliferative subtypes. Patients with the latter subtype may experience serious vision impairments, including vision loss. Vascular endothelial growth factor inhibitors such as bevacizumab have been proposed as a treatment to improve visual function in patients with sickle cell retinopathy.

This evidence review addresses the use of circulating tumor-tissue-viral modified (TTMV) human papillomavirus (HPV) DNA testing for cancer management. The purpose of tumor-informed TTMV-HPV DNA testing in individuals with HPV-related cancer is to predict disease outcomes to inform treatment decisions and to monitor for recurrence following treatment.

ADSTILADRIN is a non-replicating adenoviral vector-based gene therapy indicated for the treatment of adult patients with high-risk Bacillus CalmetteGuérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. <a id="

ADSTILADRIN is a non-replicating adenoviral vector-based gene therapy indicated for the treatment of adult patients with high-risk Bacillus CalmetteGuérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. <a id="

Nasal obstruction is defined clinically as a patient symptom that presents as a sensation of reduced or insufficient airflow through the nose. Nasal valve collapse (NVC) is a readily identifiable cause of nasal obstruction. Specifically, the internal nasal valve represents the narrowest portion of the nasal airway with the upper lateral nasal cartilages present as supporting structures. The external nasal valve is an area of potential dynamic collapse that is supported by the lower lateral cartilages. Damaged or weakened cartilage will further decrease airway capacity and increase airflow resistance and may be associated with symptoms of obstruction. Patients with NVC may be treated with nonsurgical interventions in an attempt to increase the airway capacity but severe symptoms and anatomic distortion are treated with surgical cartilage graft procedures. The application of radiofrequency volumetric tissue reduction for nasal obstruction has been proposed as a less invasive means to treat nasal obstruction due to internal NVC. By utilizing RF energy, the treatment aims to provide relief with reduced recovery times and fewer complications compared to traditional surgical methods.

The term "Discontinued Procedure" designates a surgical or diagnostic procedure provided by a physician or other health care professional that was less than usually required for the procedure as defined in the Current Procedural Terminology (CPT®) book. This policy describes the billing instructions and guidelines when billing for a discontinued procedure using modifiers 73 or 74. Modifier 73: Discontinued Outpatient Hospital/Ambulatory Surgery Center (ASC) Procedure Prior to the Administration of Anesthesia: Due to extenuating circumstances or those that threaten the well-being of the patient, the physician may cancel a surgical or diagnostic procedure subsequent to the patient's surgical preparation (including sedation when provided, and being taken to the room where the procedure is to be performed), but prior to the administration of anesthesia (local, regional block(s) or general). Under these circumstances, the intended service that is prepared for but cancelled can be reported by its usual procedure number and the addition of modifier 73. Note: The elective cancellation of a service prior to the administration of anesthesia and/or surgical preparation of the patient should not be reported. For physician reporting of a discontinued procedure, see modifier 53. Modifier 74 Discontinued Outpatient Hospital/Ambulatory Surgery Center (ASC) Procedure After Administration of Anesthesia: Due to extenuating circumstances or those that threaten the well-being of the patient, the physician may terminate a surgical or diagnostic procedure after the administration of anesthesia (local, regional block(s), general) or after the procedure was started (incision made, intubation started, scope inserted, etc.). Under these circumstances, the procedure started but terminated can be reported by its usual procedure number and the addition of modifier 74. Note: The elective cancellation of a service prior to the administration of anesthesia and/or surgical preparation of the patient should not be reported. For physician reporting of a discontinued procedure, see modifier 53. <a id="

(Leuprolide acetate) – A drug that is a manufactured version of a hormone. It is a hormone-releasing hormone agonist which is a synthetic analog of naturally occurring gonadotropin-releasing hormone (GnRH) possessing greater potency than the natural hormone. Lupron Depot is indicated for several conditions, including prostate cancer, endometriosis, and uterine leiomyomas. <a id="

SOLIRIS is a complement inhibitor indicated for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis, the treatment of patients with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy, the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AchR) antibody positive & the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive.

Ravulizumab-cwvz is a complement inhibitor indicated as a treatment for adult patients, 18 years and older, with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis. <a id="

Ruconest is a recombinant C1 esterase inhibitor indicated for the treatment of acute attacks of hereditary angioedema (HAE). Mechanism: C1 esterase inhibitor is a complement protein regulating the kallikrein–bradykinin pathway. Deficiency or dysfunction leads to recurrent angioedema in HAE. Clinical relevance: HAE is a rare, life-threatening disorder characterized by swelling in extremities, GI tract, face, and airway, with risk of asphyxiation. FDA Indication: Treatment of acute attacks of HAE in patients ≥13 years. <a id="

Omalizumab is an anti-IgE monoclonal antibody produced by recombinant DNA technology using Chinese hamster ovaries. It binds specifically to human immunoglobulin E (IgE) and inhibits the binding of IgE to mast cells and basophils. The reduction in IgE binding limits the allergic response. <a id="

Natalizumab (Tysabri) is a humanized monoclonal antibody that binds to alpha-4 integrin expressed on the surface of activated T-cells. Alpha-4 integrin is a selective adhesion molecule that facilitates adhesion and subsequent leukocyte migration into areas of inflammation. Pre-clinical data has demonstrated the benefits of integrin inhibition, including mucosal healing and a reduction of inflammation. Leukocyte adhesion in endothelial cells is a multistep process that involves chemokine receptors and active integrins. Ultimately, natalizumab blocks both alpha-4 subunit of alpha-4 beta-1 (vascular cellular adhesion molecule of VCAM-1) and alpha-4 beta-7 (mucosal addressin [MAD] CAM-1). The site of action is not organ specific and other sites such as the brain, bone marrow, and kidneys are affected. This has led to studies of natalizumab in diverse chronic inflammatory diseases including MS and CD.

Stelara is a human IgG1κ monoclonal antibody that binds with high affinity and specificity to the p40 protein subunit used by both the interleukin (IL)-12 and IL-23 naturally occurring cytokines. IL-12 and IL-23 are involved in inflammatory and immune responses, such as natural killer cell activation and CD4+ T-cell differentiation and activation. Ustekinumab is used to treat plaque psoriasis, a certain type of arthritis (psoriatic arthritis), or certain bowel conditions (Crohn's disease, ulcerative colitis). <a id="

Golimumab is in a class of drugs called biologics. Golimumab is a treatment for adults with moderate to severe rheumatoid arthritis, active psoriatic arthritis, or active ankylosing spondylitis. It is injected under the skin to reduce signs and symptoms of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, such as joint swelling, pain, fatigue, and length of morning stiffness. Golimumab is commonly known as Simponi®. It can also be given as an infusion. <a id="

Ocrelizumab is a humanized monoclonal antibody that is directed against CD20-expressing B-cells. CD20 is a cell surface antigen that is present on pre-B and mature B lymphocytes. Ocrelizumab binds to CD20 on B lymphocytes and causes antibody-dependent cellular cytolysis and complement-mediated lysis. <a id="

Nucala (mepolizumab) is an interleukin-5 receptor antagonist indicated for add-on maintenance treatment of patients aged 6 years and older with severe asthma and with an eosinophilic phenotype, for add-on maintenance treatment of adult patients 18 years and older with chronic rhinosinusitis with nasal polyps (CRSwNP), the treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA), for add-on maintenance treatment of adult patients with inadequately controlled chronic obstructive pulmonary disease (COPD) and an eosinophilic phenotype, and the treatment of adult and pediatric patients aged 12 years and older with hypereosinophilic syndrome (HES) for ≥6 months without an identifiable non-hematologic secondary cause. <a id="

Somatuline® Depot; Lanreotide is used to treat people with acromegaly (condition in which the body produces too much growth hormone, causing enlargement of the hands, feet, and facial features; joint pain; and other symptoms) who have not successfully, or cannot be treated with surgery or radiation. Lanreotide injection is also used to treat people with neuroendocrine tumors in the gastrointestinal (GI) tract or the pancreas (GEP-NETs) that have spread or cannot be removed by surgery. Lanreotide injection is in a class of medications called somatostatin agonists. It works by decreasing the amounts of certain natural substances produced by the body. <a id="

Benralizumab is an interleukin-5 antagonist monoclonal antibody (IgG1 kappa) for the add-on maintenance treatment of severe asthma in patients age 12 years and older with an eosinophilic phenotype. <a id="

Vedolizumab is a recombinant human IgG1 monoclonal antibody produced in Chinese hamster ovaries. It binds to a human alpha 4 beta 7 integrin site and blocks the interaction of this integrin with mucosal addressin adhesion molecules. This inhibits the migration of memory T-lymphocytes across the endothelium into the inflamed gastrointestinal tissue. This interaction is thought to be an important contributor to the chronic inflammation of ulcerative colitis and Crohn's disease. <a id="

FYARRO™ (nab-sirolimus) is an mTOR inhibitor formulated as sirolimus protein-bound particles (albumin-bound) for IV infusion. FDA Indication: Treatment of adults with locally advanced unresectable or metastatic malignant PEComa. (Approved November 2021). Mechanism: Inhibits the mTOR pathway, a key driver of PEComa progression. Clinical Data: The AMPECT Phase 2 trial showed an objective response rate of ~39%, with durable responses in patients with advanced malignant PEComa.

XENPOZYME® (olipudase alfa-rpcp) is an enzyme replacement therapy (ERT) for the treatment of non-CNS manifestations of ASMD in both adults and pediatric patients. Mechanism: Recombinant human acid sphingomyelinase that hydrolyzes accumulated sphingomyelin in lysosomes, reducing lipid storage. Disease background: ASMD (Niemann-Pick disease types A/B) is an autosomal recessive lysosomal storage disorder caused by SMPD1 gene mutations, leading to deficient ASM activity, sphingomyelin buildup, hepatosplenomegaly, pulmonary dysfunction, and systemic morbidity. Clinical trials (ASCEND, ASCEND-Peds): demonstrated significant reductions in spleen/liver volume and improvements in pulmonary function (DLCO). FDA Indication: Approved for non-CNS manifestations of ASMD (July 2022; PI revised December 2023).

OPDUALAG (nivolumab + relatlimab-rmbw) is a fixed-dose combination of two immune checkpoint inhibitors: Nivolumab: Anti–PD-1 monoclonal antibody, blocking PD-1 interaction with PD-L1/PD-L2, enhancing T-cell anti-tumor response. Relatlimab: Anti–LAG-3 monoclonal antibody, promoting T-cell activation, proliferation, and cytokine secretion. <a id="

Sutimlimab-jome (Enjaymo) is a monoclonal antibody that inhibits the classical complement pathway by binding to complement protein component 1 subcomponent s (C1s). This inhibition ultimately prevents hemolysis in patients with cold agglutinin disease (CAD). Sutimlimab-jome (Enjaymo) is FDA-approved for the treatment of hemolysis in adults with cold agglutinin disease (CAD). FDA approval: Indicated for treatment of hemolysis in adults with CAD (02/2022; revised PI 02/2024). Mechanism: Targets C1s, preventing C3 activation and subsequent extravascular hemolysis. Clinical trials (CARDINAL, CADENZA): demonstrated rapid increase in hemoglobin, reduction in transfusion needs, and improvement in fatigue scores. Special notes: Vaccination against encapsulated bacteria (pneumococcal, meningococcal, Hib) required before initiation. <a id="

Teclistamab (Tecvayli) is a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engaging antibody for the treatment of adult patients with relapsed or refractory multiple myeloma (MM) who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody. This indication was approved under accelerated approval based on response rate,and continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). Teclistamab binds to the CD3 receptor expressed on the surface of T-cells and BCMA expressed on the surface of multiple myeloma cells and some healthy B-lineage cells. In vitro, teclistamab activated T-cells, caused the release of various proinflammatory cytokines, and resulted in the lysis of multiple myeloma cells. Teclistamab (Tecvayli) has boxed warnings due to cytokine release syndrome (CRS) and neurologic toxicity. Tecvayli is available only through a restricted program called the TECVAYLI and TALVEY Risk Evaluation and Mitigation Strategy (REMS). <a id="

Imjudo (tremelimumab-actl) is a cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) blocking antibody indicated: In combination with durvalumab for the treatment of adults with unresectable hepatocellular carcinoma (uHCC). In combination with durvalumab + platinum-based chemotherapy for adults with metastatic non-small cell lung cancer (NSCLC), without sensitizing EGFR mutations or ALK genomic aberrations. <a id="

Briumvi (ublituximab-xiiy) is a CD20-directed monoclonal antibody indicated for the treatment of adults with relapsing forms of multiple sclerosis (MS), including: Clinically isolated syndrome (CIS), Relapsing-remitting MS (RRMS), Active secondary progressive MS (SPMS). It works by binding to CD20 on the surface of B lymphocytes, inducing antibody-dependent and complement-mediated cell lysis, thereby reducing relapse frequency and delaying disability progression. <a id="

Elahere (mirvetuximab soravtansine-gynx) is a folate receptor alpha (FRα)-directed antibody–drug conjugate (ADC) linked to a microtubule inhibitor. It is indicated for the treatment of adults with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens.

Rybrevant (amivantamab-vmjw) is a bispecific EGF receptor-directed and MET receptor-directed antibody indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring: EGFR exon 20 insertion mutations, whose disease has progressed on or after platinum-based chemotherapy, OR EGFR exon 19 deletions or exon 21 (L858R) substitution mutations, as detected by an FDA-approved test, in combination with chemotherapy or lazertinib. <a id="

Monjuvi (tafasitamab-cxix) is a CD19-directed cytolytic antibody indicated, in combination with lenalidomide, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low-grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT). Tafasitamab binds to the CD19 antigen on pre-B and mature B lymphocytes, inducing B-cell lysis via apoptosis and immune effector mechanisms including antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis. <a id="

Margenza (margetuximab-cmkb) is a HER2/neu receptor antagonist indicated, in combination with chemotherapy, for the treatment of adult patients with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease. Margetuximab-cmkb is a chimeric Fc-engineered IgG1 kappa monoclonal antibody that binds to the extracellular domain of the HER2 protein. Upon binding, it inhibits tumor cell proliferation, reduces shedding of the HER2 extracellular domain, and mediates antibody-dependent cellular cytotoxicity (ADCC). >

Jemperli is a programmed death receptor-1 (PD-1)–blocking antibody indicated for: Endometrial Cancer • in combination with carboplatin and paclitaxel, followed by JEMPERLI as a single agent, for the treatment of adult patients with primary advanced or recurrent endometrial cancer (EC). • as a single agent for the treatment of adult patients with mismatch repair deficient (dMMR) recurrent or advanced EC, as determined by an FDA approved test, that has progressed on or following prior treatment with a platinum-containing regimen in any setting and are not candidates for curative surgery or radiation Mismatch Repair Deficient Recurrent or Advanced Solid Tumors • as a single agent for the treatment of adult patients with dMMR recurrent or advanced solid tumors, as determined by an FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). Dostarlimab-gxly (Jemperli) is a monoclonal antibody that works by targeting the programmed death-1 receptor (PD-1), which is involved in T-cell immune surveillance of tumors. Binding of the PD-1 receptor results in blockade of the PD-1 and PD-2 ligands which generates an anti-tumor immune response and decreased tumor growth. Mismatch repair deficient (dMMR) tumors are expressed in various cancers and have high mutation rates due to the inability to repair DNA replication errors. These tumors have higher levels of neoantigens and have been found to be responsive to PD-1 targeted immunotherapy. Guidelines: NCCN 2025 lists dostarlimab as preferred for dMMR/MSI-H endometrial cancer (monotherapy) and as Category 1 with chemo in frontline advanced EC. <a id="

Danyelza (naxitamab-gqgk) is a GD2-binding monoclonal antibody indicated, in combination with granulocyte-macrophage colony-stimulating factor (GMCSF), for the treatment of pediatric patients 1 year of age and older and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response, or stable disease to prior therapy. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Adakveo® is an IV P-selectin inhibitor approved by the FDA for reducing vaso-occlusive crises (VOC) in patients with sickle cell disease (SCD) aged ≥16 years

BEOVU is a prescription medicine used to treat Neovascular (Wet) Age-Related Macular Degeneration (AMD) and Diabetic Macular Edema (DME). Beovu is a recombinant human vascular endothelial growth factor inhibitor. <a id="

ADAKVEO is a prescription medicine used to treat the symptoms of Sickle Cell Disease. Adakveo may be used alone or with other medications. Adakveo belongs to a class of drugs called P-Selectin Inhibitor. Safety and efficacy for Adakveo has not been established in children younger than 16 years of age.

(Leuprolide acetate) – A drug that is a manufactured version of a hormone. It is a hormone-releasing hormone agonist which is a synthetic analog of naturally occurring gonadotropin-releasing hormone (GnRH) possessing greater potency than the natural hormone. Lupron Depot is indicated for several conditions, including prostate cancer, endometriosis, and uterine leiomyomas. <a id="

Studies have generally found that laser treatment can be effective at lightening port wine stains. The preponderance of evidence is on the pulsed dye laser; there is insufficient evidence from comparative studies that 1 type of laser results in more lightening than another. There is insufficient evidence that adding topical angiogenesis inhibitor to laser therapy results in better outcomes than lasers alone. There was 1 positive RCT and 1 negative RCT. No comparative studies were identified on lasers combined with any other treatments. Thus, laser treatment may be considered medically necessary in certain situations for patients with port wine stains and combination treatment is considered investigational. <a id="

Soliris is a complement inhibitor indicated for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis, treatment of patients with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AchR) antibody positive and the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive.

Ravulizumab-cwvz is a complement inhibitor indicated as a treatment for adult patients, 18 years and older, with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis. <a id="

Myasthenia gravis is an autoimmune neuromuscular disorder characterized by fluctuating motor weakness involving ocular, bulbar, limb, and/or respiratory muscles. The weakness is due to an antibody-mediated, immunologic attack directed at proteins in the postsynaptic membrane of the neuromuscular junction (acetylcholine receptors or receptor-associated proteins). Eighty to 90 percent of individuals with myasthenia gravis have autoantibodies against the acetylcholine receptor detectable in serum, and these antibodies are believed to play a central role in disease pathomechanism. Eculizumab (Soliris®) and ravulizumab-cwvz (Ultomiris®) are monoclonal antibodies that are presumed to exert a therapeutic effect in individuals with generalized myasthenia gravis through the reduction of terminal complement complex C5b-9 deposition at the neuromuscular junction. Efgartigimod alfa-fcab (Vyvgart®) is a human IgG1 antibody fragment that binds to the neonatal Fc receptor, resulting in the reduction of circulating IgG in individuals with generalized myasthenia gravis. Vygart Hytrulo is a coformulation of efgartigimod alfa and hyaluronidase (human recombinant) which can be administered subcutaneously. The addition of hyaluronidase increases the dispersion and absorption of co-administered drugs when administered subcutaneously. Rozanolixizumab-noli is a humanized IgG4 monoclonal antibody that binds to the neonatal Fc receptor resulting in the reduction of circulating IgG.

Acute hepatic porphyria (AHP) is a rare disease with a prevalence of 5 to 10 cases/100,000 people in the US and effects primarily females (age range 15 to 45 years). The induction of the enzyme aminolevulinate synthase 1 (ALAS1) results in increased production and accumulation of toxic heme intermediates delta aminolevulinic acid and porphobilinogen in the plasma and urine. The accumulation of these toxic heme intermediates results in acute attacks characterized by severe abdominal pain, muscle weakness, seizures, psychiatric dysfunction, irreversible neurologic damage, and increased risk of hepatic malignancy. Givosiran (Givlaari®) is a double-stranded small interfering RNA that causes degradation of ALAS1 mRNA in hepatocytes through RNA interference, reducing the elevated levels of liver ALAS1 mRNA. This leads to decreased circulating levels of neurotoxic intermediates aminolevulinic acid (ALA) and porphobilinogen (PBG), factors associated with attacks and other disease manifestations of acute hepatic porphyria.

Benralizumab is an interleukin-5 antagonist monoclonal antibody (IgG1 kappa) for the add-on maintenance treatment of severe asthma in patients age 12 years and older with an eosinophilic phenotype. <a id="

Mepolizumab is an interleukin-5 antagonist monoclonal antibody (IgG1 kappa) for the add-on maintenance treatment of severe asthma patients aged 12 years and older and with an eosinophilic phenotype <a id="

The hemophilias are a group of related bleeding disorders that most commonly are inherited. Inherited bleeding disorders include abnormalities of coagulation factors and platelet function; the most common of these disorders is von Willebrand disease. However, when the term "hemophilia" is used, it most often refers to the following two disorders: ●Factor VIII deficiency (hemophilia A) ●Factor IX deficiency (hemophilia B, also called Christmas disease) Patients with hemophilia, particularly those with severe disease, develop bleeding episodes that are treated with replacement of the missing factor (ie, factor VIII or factor IX concentrates). A complication of hemophilia treatment is the development of an inhibitor, which usually occurs shortly after replacement therapy has been initiated. The inhibitors are antibodies (primarily IgG) directed against the specific deficient factor. Development of inhibitors is typically assessed in relationship to the number of exposure days (ie, days on which the patient has received one or more doses of replacement factor). <a id="

Primary hyperoxalurias are a group of rare genetic diseases. There are 3 subtypes each resulting in the overproduction of oxalate by the liver. Type 1 is the most common type, which accounts for approximately 80% of cases and occurs as a result of a genetic defect in the alanine:glyoxylate aminotransferase (AGXT) gene that encodes the enzyme alanine glyoxylate aminotransferase. Defect in the enzyme results in overproduction of oxalate, which leads to deposition of calcium oxalate crystals in the kidneys and urinary tract. The result is the formation of painful and recurrent nephrolithiasis (renal stones), nephrocalcinosis, and renal failure. Compromised renal function exacerbates the disease as the excess oxalate can no longer be effectively excreted, resulting in subsequent accumulation and crystallization in bones, eyes, skin, and heart, leading to severe illness and death. Lumasiran is a subcutaneously administered RNA interference (RNAi) therapeutic that silences the HAO1 gene, which encodes for a glycolate oxidase enzyme. By silencing the HAO1 gene, levels of glycolate oxidase are depleted, decreasing production of oxalate, the metabolite that directly contributes to the pathophysiology of primary hyperoxaluria type 1.

Hereditary transthyretin-mediated amyloidosis (hATTR) is a rare, progressive, and fatal autosomal dominant genetic disease in which a variant in the transthyretin gene results in the production of misfolded insoluble transthyretin protein which accumulates as amyloid fibrils (i.e., amyloidosis) in multiple organs of the body such as the liver, nerves, heart, and kidneys causing disruption of organ tissue structure and function. Historically, hATTR was classified into familial amyloid polyneuropathy or familial amyloid cardiomyopathy. However, it is now recognized that most patients manifest signs and symptoms of both syndromes over the course of their disease and therefore the current clinical approach treats familial amyloid polyneuropathy and familial amyloid cardiomyopathy as 1 hereditary disease (polyneuropathy of hATTR) with a spectrum of clinical manifestations.

Immune globulin (also referred to as gamma globulin or immunoglobulin) is a therapeutic compound prepared from pools of plasma obtained from several thousand healthy blood donors that contains antibodies to a wide spectrum of antigens. Immune globulin has been utilized for immune deficiencies identified in individuals with inherited or acquired immunodeficiencies and is used for its capacity in combating infection as a replacement therapy and for its anti-inflammatory and immunomodulating effects. The appropriate use of immune globulin can decrease morbidity and mortality and improve quality of life.1,2 <a id="

C-1 esterase inhibitor protein is one of nine complement proteins found in the blood that works with the body's immune system in coagulation, fighting disease and the development of inflammation. Hereditary angioedema (HAE) is a rare, but life-threatening genetic disorder of the immune system characterized by edema in various parts of the body, including the extremities, intestines, face, and airway. <a id="

Vascular endothelial growth factor has been implicated in the pathogenesis of a variety of ocular vascular conditions characterized by choroidal neovascularization (CNV) and macular edema. <a id="

Endogenous erythropoietin is a glycoprotein hematopoietic growth factor that regulates hemoglobin levels in response to changes in the blood oxygen concentration. Erythropoiesis-stimulating agents (ESAs; eg, epoetin alfa, pegylated epoetin beta, darbepoetin) are produced using recombinant DNA technologies and have pharmacologic properties similar to endogenous erythropoietin. The primary clinical use of ESAs is to treat chronic anemia. <a id="

Infliximab (Remicade®) is a tumor necrosis factor α (TNF-α) blocking agent approved by the U.S. Food and Drug Administration (FDA) for the treatment of rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, and ulcerative colitis. Infliximab is also being considered as an off-label treatment for systemic juvenile idiopathic arthritis, select rheumatic and autoimmune conditions, vasculitides, and nonrheumatic musculoskeletal conditions. This evidence review focuses on the off-label group of indications.

Stelara is a human IgG1κ monoclonal antibody that binds with high affinity and specificity to the p40 protein subunit used by both the interleukin (IL)-12 and IL-23 naturally occurring cytokines. IL-12 and IL-23 are involved in inflammatory and immune responses, such as natural killer cell activation and CD4+ T-cell differentiation and activation. Ustekinumab is used to treat plaque psoriasis, a certain type of arthritis (psoriatic arthritis), or certain bowel conditions (Crohn's disease, ulcerative colitis). <a id="

Golimumab is in a class of drugs called biologics. Golimumab is a treatment for adults with moderate to severe rheumatoid arthritis, active psoriatic arthritis, or active ankylosing spondylitis. It is injected under the skin to reduce signs and symptoms of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, such as joint swelling, pain, fatigue, and length of morning stiffness. Golimumab is commonly known as Simponi®. It can also be given as an infusion. <a id="

Somatuline® Depot; Lanreotide is used to treat people with acromegaly (condition in which the body produces too much growth hormone, causing enlargement of the hands, feet, and facial features; joint pain; and other symptoms) who have not successfully, or cannot be treated with surgery or radiation. Lanreotide injection is also used to treat people with neuroendocrine tumors in the gastrointestinal (GI) tract or the pancreas (GEP-NETs) that have spread or cannot be removed by surgery. Lanreotide injection is in a class of medications called somatostatin agonists. It works by decreasing the amounts of certain natural substances produced by the body. <a id="

White blood cell growth factors, also known as granulocyte colony stimulating factors (G-CSF), are administered to enhance recovery of blood related functions in neutropenia (low white blood count) including febrile neutropenia (FN). G-CSF is classified as a recombinant hematopoietic stimulant. This is not a cancer chemotherapy agent. It is a class II hematopoietic growth factor which acts on progenitor cells capable of forming a single differentiated cell type, the neutrophilic granulocyte, and is thus lineage-specific. CSFs are also utilized to decrease the incidence and severity of infection associated with select disease-related and drug-related myelosuppression (inhibition of bone marrow function). General Information Pegfilgrastim is approved by the Food and Drug Administration to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. Prophylactic use of pegfilgrastim in patients undergoing chemotherapy reduces the risk of febrile neutropenia and infections. Prophylactic therapy can be considered for patients receiving myelosuppressive chemotherapy if the risk of febrile neutropenia is 20% or greater. Pegfilgrastim-jmdb, pegfilgrastim-cbqv, pegfilgrastim-bmez and pegfilgrastim-apgf are leukocyte growth factors indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti- cancer drugs associated with a clinically significant incidence of febrile neutropenia. Pegfilgrastim-jmdb, pegfilgrastim-cbqv, pegfilgrastim-bmez and pegfilgrastim-apgf are biosimilar* to pegfilgrastim. *Biosimilar means that the biological product is approved based on data demonstrating that it is highly similar to an FDA-approved biological product, known as a reference product, and that there are no clinically meaningful differences between the biosimilar product and the reference product. Biosimilarity of pegfilgrastim-jmdb, pegfilgrastim-cbqv, pegfilgrastim-bmez and pegfilgrastim-apgf has been demonstrated for the condition(s) of use (e.g., indication(s), dosing regimen(s), strength(s), dosage form(s), and route(s) of administration described in its Full Prescribing Information). <a id="

Bevacizumab is a humanized monoclonal antibody directed against Vascular Endothelial Growth Factor A (VEGF-A). Vascular Endothelial Growth Factors (VEGF) and their receptors (VEGF-R) contribute to the tumor growth and to the metastasis through the promotion of the angiogenesis. Off-label non-oncologic uses of Bevacizumab are not discussed in this medical policy. <a id="

Trastuzumab is a monoclonal antibody, one of a group of drugs designed to attack specific cancer cells. Trastuzumab – Trastuzumab Biologics Trastuzumab’s targets are cancer cells that overexpress an oncogene called HER2 or HER2/neu, which occurs in high numbers in about 25 to 30 percent of breast cancers. According to the National Comprehensive Cancer Network (NCCN), breast cancers can be categorized as being HER2 positive or HER2 negative. HER2-positive breast cancer is faster growing and considered more aggressive. Studies indicate that the drug trastuzumab (Herceptin) is effective in treatment of HER2-positive early stage breast cancer and HER2-positive metastatic breast cancer. Trastuzumab is not effective in the treatment of HER2-negative breast cancers. There are two methods of testing for HER2 tumor status in women with breast cancer: immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). HER2 test results are interpreted as follows: HER2 positive status is IHC 3+ or FISH positive HER2 negative status is IHC 0, 1+ or FISH negative A borderline IHC result of 2+ should be followed by performing a FISH test. A borderline FISH result of an average HER2 gene/chromosome 17 ratio of 1.8 to 2.2 (or an average of greater than 4 to less than 6 HER2 gene copies/cell) should be followed by one of the following: Counting additional cells in the tissue sample Retesting with FISH Performing an IHC test Results from both tests are used in the clinical setting, and the results of the tests influence treatment choices for women with breast cancer. The pathology laboratory where the HER2 testing is done should be accredited to perform such testing. It should have quality control procedures in place to ensure that the test is done correctly, and a quality assurance plan to validate (i.e., determine the accuracy of) the HER2 test results. <a id="

Rituximab is a genetically engineered chimeric murine/human monoclonal IgG1 kappa antibody directed against the CD20 antigen." Rituximab binds specifically to the antigen CD20 (human B-lymphocyte-restricted differentiation antigen, Bp35), a hydrophobic transmembrane protein with a molecular weight of approximately 35 kD located on pre-B and mature B lymphocytes. The antigen is expressed on > 90% of B-cell Non-Hodgkin’s Lymphomas (NHL), but the antigen is not found on hematopoietic stem cells, pro-B-cells, normal plasma cells or other normal tissues. B cells are believed to play a role in the pathogenesis of rheumatoid arthritis (RA) and associated chronic synovitis. In Non-Hodgkin’s Lymphoma (NHL) patients, administration of rituximab resulted in depletion of circulating and tissue-based B cells. In Wegeners Granulomatosis with Polyangiitis and Microscopic Polyangiitis patients, peripheral blood CD19 B-cells depleted to less than 10 cells/µl following the first two infusions of rituximab, and remained at that level in most (84%) patients through Month 6. By Month 12, the majority of patients (81%) showed signs of B-cell return with counts >10 cells/µL. <a id="

Viscosupplementation therapy is part of the therapy used in the treatment of osteoarthritis of the knee. Osteoarthritis results from articular cartilage failure due to the complex interplay of genetic, metabolic, biochemical and biomechanical factors with a secondary component of inflammation. In most patients the initiating mechanism is damage to the articular cartilage either as a single large injury or a series of repeated smaller injuries. The primary symptom of osteoarthritis of the knee is pain, however, because cartilage is aneural, significant radiographic findings are often noted in asymptomatic individuals imaged for other reasons. <a id="

Atrial fibrillation (AF) is the most common type of cardiac arrhythmia. Stroke associated with AF is primarily embolic, tends to be more severe than the typical ischemic stroke, and causes higher rates of mortality and disability. As a result, stroke prevention is one of the main goals of AF treatment. Treatment with anticoagulant medications is a first-line approach to stroke prevention in individuals with AF, although occlusion of the left atrial appendage (LAA) may offer a non-pharmacological alternative to anticoagulant medications for those with a contraindication or intolerance to long-term anticoagulant use or with poor anticoagulant adherence. Multiple surgical techniques may be used to excise or occlude the LAA. One device, the AtriClip Left Atrial Appendage Exclusion System, has approval from the U.S. Food and Drug Administration for surgical LAA occlusion for stroke prevention in patients with AF.

The branch of dentistry that is responsible for the study, prevention, diagnosis and treatment of anomalies in the shape, position, relationship and function of dentomaxillofacial structures. <a id="

Temporomandibular joint disorder (TMJD) refers to a group of disorders characterized by pain in the temporomandibular joint and surrounding tissues. Initial conservative therapy is generally recommended; there are also a variety of nonsurgical and surgical treatment possibilities for individuals whose symptoms persist.