A review and update on orphan drugs for the treatment of noninfectious uveitis

Figures & data

Table 1 Orphan drugs approved by the US Food and Drug Administration for use in systemic disease/organ transplantation that have not received orphan drug approval for use in uveitis

Generic names	Approved labeled indication
Methotrexate	High-dose methotrexate for use with leucovorin rescue in patients with nonmetastatic osteosarcoma who have undergone surgical resection or amputation for the primary tumor
Tacrolimus	Prophylaxis of organ rejection in kidney transplant patients converted from tacrolimus immediate release formulations in combination with other immunosuppressants; prophylaxis of organ rejection in patients receiving allogenic heart transplants
Infliximab	For reducing signs and symptoms, and inducing and maintaining clinical remission in pediatric patients with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy; for reducing signs and symptoms, and inducing and maintaining clinical remission in pediatric patients aged ≥6 years with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy; treatment of moderately to severely active Crohn’s disease for the reduction of the signs and symptoms in patients who have an inadequate response to conventional therapies; and treatment of patients with fistulizing Crohn’s disease for the reduction in the number of draining enterocutaneous fistula(s)
Interferon	Treatment of chronic myelogenous leukemia (interferon α-2a); treatment of selected patients with AIDS-related Kaposi’s sarcoma (interferon α-2b [recombinant]); treatment of relapsing forms of multiple sclerosis to slow the accumulation of physical disability and decrease the frequency of clinical exacerbations (interferon β-1a); in ambulatory patients with relapsing–remitting multiple sclerosis to reduce the frequency of clinical exacerbations (interferon β-1b); delaying time to disease progression in patients with severe, malignant osteopetrosis (interferon γ-1b); adjuvant treatment of melanoma with microscopic or gross nodal involvement within 84 days of definitive surgical resection including complete lymphadenectomy (peginterferon α-2b)
Rituximab	Treatment of patients previously untreated for CD20-positive chronic lymphocytic leukemia in combination with fludarbine and cyclophosphamide; for the use of Rituxan^® (rituximab) in combination with glucocorticoids for the treatment of patients with Wegener’s granulomatosis and microscopic polyangiitis
Tocilizumab	Treatment of active polyarticular juvenile idiopathic arthritis in patients aged 2 through 16 years
Anakinra	Treatment of neonatal-onset multisystem inflammatory disease
Canakinumab	Treatment of cryopyrin-associated periodic syndromes, in adults and children aged ≥4 years; treatment of active systemic juvenile idiopathic arthritis in patients aged 2 through 16 years
Alemtuzumab	The treatment of patients with B-cell chronic lymphocytic leukemia who have been treated with alkylating agents and who have failed fludarabine therapy

Table 2 Approved orphan drugs by the US Food and Drug Administration to be in systemic diseases and/or organ transplantation while not received “orphan drug approval” to be used in uveitis (II) – mechanism and using

Medication	Mechanism of action	Dosage/route	Potential side effects
Methotrexate	Antimetabolites/inhibits dihydrate folate reductase	7.5–25 mg per week given with folic acid, p.o., S.C.	Gastrointestinal disturbance, hepatotoxicity, oral ulcers, fatigue, alopecia, bone marrow suppression, pneumonitis, fetal loss, and infections
Tacrolimus	T-cell inhibitor/calcineurin inhibitor	0.1–0.15 mg/kg/day, p.o.	Nephrotoxicity, hypertension, diabetes mellitus, electrolyte imbalance, and infections
Infliximab	Anti-TNFα	3–5 mg/kg loading at weeks 0, 2, and 6, then maintenance 3–10 mg/kg every 4–8 weeks; maximal dose 20 mg/kg in children, I.V.	Susceptibility to infections, including reactivation of tuberculosis, histoplasmosis, hepatitis B, and fungal infection; hypersensitivity reactions; demyelinating disease; lupus-like syndrome; malignancy; thromboembolic events; congestive heart failure
Interferon α-2a	Biologic/antiimmunomodulatory effects	3–9 million units once daily to three times weekly, S.C.	Injection-site reaction, flu-like syndrome, fatigue, depression, neutropenia, elevation of liver enzymes, and rarely INF α-2a retinopathy
Rituximab	Biologic/anti-CD20	1,000 mg or 375 mg/m^2 given twice at 2-week intervals, I.V.	Susceptibility to infections, infusion reactions, gastrointestinal disturbance, cardiovascular events, muscle spasm, and headache and multifocal leukoencephalopathy
Tocilizumab	Cytokine receptor antibodies/anti-IL-6 receptor	Initial 4 mg/kg every 4 weeks then increase to 8–12 mg/kg every 2–4 weeks, I.V.	Serious infections, hypersensitivity reactions, hypercholesterolemia, and gastrointestinal perforation
Anakinra	Cytokine receptor antibodies/anti-IL1 receptor	100 mg daily, S.C.	Injection-site reaction, infections, headache, gastrointestinal disturbance, and fever
Canakinumab	Monoclonal antibody against IL-1β	Systemic juvenile idiopathic arthritis: 4 mg/kg (max 300 mg) S.C. every 4 weeks; cryopyrin-associated periodic syndromes, 2–3 mg/kg SQ every 8 weeks, I.V., S.C.	Susceptibility to infections, headache, nausea, and abdominal pain
Alemtuzumab	Monoclonal antibody against CD52	30 mg I.V., 3 days per week for 12 weeks, I.V.	Cytopenias, infusion reactions, infections, gastrointestinal disturbance, and insomnia

Abbreviations: IL, interleukin; INF, interferon; I.V., intravenously; p.o., oral administration; S.C., subcutaneously; TNF, tumor necrosis factor; SQ, subcutaneous.