Table I.
Examples of Therapeutic Proteins Approved for Autoimmune and Other Inflammatory Conditions
| Therapeutic | Trade name | Modality, target(s), and/or mode of action | Inflammatory indication(s)a | Dosing regimenb |
|---|---|---|---|---|
| Type I alpha-interferon (IFN-α), interferon alfacon 1, consensus interferon | Infergen | Recombinant (non-naturally) occurring type-I IFN-α; immunoregulator | Chronic hepatitis C infection | 15 μg daily SC |
| Interferon-α2a (IFN-α2a) | Roferon-A | Recombinant IFN-α2a; immunoregulator | Chronic hepatitis C infection | 3 MIU three times a week SC |
| PegInterferon-α2a | Pegasys | Recombinant IFN-α2a conjugated to PEG (40 kDa); immunoregulator | Chronic hepatitis C infection | 180 μg QW SC |
| Interferon-α2b (IFN-α2b) | Intron A | Recombinant IFN-α2b; immunoregulator | Chronic hepatitis C, hepatitis B infections | Hepatitis C:3 MIU TIW SC or IM |
| Hepatitis B: 5 MIU QD or 10 MIU TIW SC or IM | ||||
| PegInterferon-α2b | Peg-Intron | Recombinant IFNα2b conjugated to PEG (12 kDa); immunoregulator | Chronic hepatitis C infection | 1.0 μg/kg QW SC |
| Interferon-αn3 (IFN-αn3) | Alferon N | Nonrecombinant human IFN-α-n3 purified from pooled human leukocytes; immunoregulator | Condylomata acuminata (genital warts) | 250,000 IU per wart, twice weekly |
| Interferon-β1a (rIFN-β1a) | Avonex | Recombinant rIFN-β1a; antiviral and immunoregulator | MS | 30 μg QW IM |
| Interferon-β1b (rIFN-β) | Betaseron | Recombinant rIFN-β1b; antiviral and immunoregulator | MS | Initial: titration 0.0625 to 0.25 mg Q2D SC |
| Maintenance: 0.25 mg Q2D SC | ||||
| Omalizumab | Xolair | Humanized IgG1 directed against IgE and inhibits IgE binding to the high-affinity IgE receptor on mast cells and basophils | Asthma | Titrated to total serum IgE levels: 150–375 mg Q2W or Q4W SC |
| Rituximab | Rituxan | Chimeric (human/mouse) IgG1 that binds CD20, a cell surface protein found on normal and some malignant B cells, resulting in selective depletion of CD20+ B cells | RA | Two 1-g IV infusions separated by 2 weeks repeated every 24 weeks |
| Antithymocyte globulin (rabbit) | Thymoglobulin | Purified, pasteurized, IgG, obtained by immunization of rabbits with human thymocytes; immunosuppressant that selectively depletes T cells | Acute kidney transplant rejection, aplastic anemia | 1.5 mg/kg IV QD |
| Basiliximab | Simulect | Chimeric (human/mouse) IgG1 that binds to IL-2Rα chain, expressed on the surface of activated T lymphocytes, inhibiting the IL2-mediated activation of lymphocytes | Prophylaxis against allograft rejection in renal transplant patients | Two 20 mg IV doses |
| Daclizumab | Zenapax | Humanized IgG1 that binds to IL-2Rα chain, inhibiting the IL2-mediated activation of lymphocytes | Prophylaxis against acute allograft rejection in patients receiving renal transplants | 1 mg/kg IV Q2W transplant |
| Muromonab-CD3 | Orthoclone, OKT3 | Mouse mAb that binds CD3 and results in selective depletion of CD3+ T cells | Acute renal allograft rejection, steroid-resistant cardiac or hepatic allograft rejection | 5 mg/day IV for 10–14 days |
| Abatacept | Orencia | Recombinant human fusion protein consisting of the ECD of CTLA4 and the Fc (IgG1 modified) that inhibits T cell activation by binding to CD80 and CD86, thereby blocking interaction with CD28 | JIA, RA | JIA and RA “IV regimen”: |
| 500–1,000 mg or 10 mg/kg (based on body weight) Q2W 3 doses, followed by maintenance Q4W | ||||
| RA “SC regimen”: initial dose given by IV as above followed by 125 mg SC weekly | ||||
| Anakinra | Antril, Kineret | Recombinant form of IL-1R antagonist (IL-1Ra) that binds to IL-1 and inhibits it binding to IL-1 type 1 receptor (IL-1RI) | RA | 100 mg SC daily |
| Rilonacept | Arcalyst | Recombinant human fusion protein consisting of ECD of IL-1RI, IL-1 receptor accessory protein, and Fc (IgG1) that binds to IL-1 and inhibits its binding to the IL-1Rs | Cryopyrin-associated periodic syndromes | 160 mg SC QW, with 320 mg SC loading dose |
| Canakinumab | Llaris | Humanized IgG1 directed against IL-1β inhibits its binding to the IL-1Rs | Cryopyrin-associated periodic syndromes | 150 mg SC Q8W |
| Adalimumab | Humira | Human IgG1 that binds to soluble and membrane TNF-α and inhibits its binding to TNFRs | AS, CD, JIA plaque psoriasis, psoriatic arthritis, RA | RA, AS psoriatic arthritis: 40 mg SC Q2W |
| JIA: (15–30 kg) 20 mg SC Q2W, (≥30 kg), 60 mg SC Q2W | ||||
| CD: Initial: 160 mg SC, 80 mg 1 week later | ||||
| Maintenance: 40 mg SC Q2W | ||||
| Plaque psoriasis: initial: 80 mg SC | ||||
| Maintenance: 40 mg SC Q2W (starting the week following the initial dose) | ||||
| Etanercept | Enbrel | Recombinant soluble human TNF-R1 and Fc (IgG1) fusion protein that binds to soluble and membrane TNF-α and inhibits its binding to TNFRs | AS, JIA, plaque psoriasis, psoriatic arthritis, RA | RA, psoriatic arthritis: 50 mg SC QW |
| JIA: 0.8 mg/kg (max, 50 mg) SC QW | ||||
| Psoriasis: 50 mg SC twice weekly every 3 months | ||||
| Infliximab | Remicade | Chimeric (mouse/human) IgG1 that binds to soluble and membrane TNF-α and inhibits its binding to TNFRs; induction of activated T cell and macrophage apoptosis | AS, CD, plaque psoriasis, psoriatic arthritis, RA, UC | CD, UC, psoriatic arthritis, and plaque psoriasis: Initial: 5 mg/kg IV 0, 2, and 6 weeks |
| Maintenance: 5 mg/kg IV Q8W | ||||
| RA: 3 mg/kg IV at weeks 0, 2, and 6 | ||||
| Maintenance: 3 mg/kg IV Q8W | ||||
| AS: 3 mg/kg IV at weeks 0, 2, and 6 | ||||
| Maintenance: 3 mg/kg IV Q6W | ||||
| Certolizumab pegol | Cimzia | Humanized Fab-PEG conjugate that binds to soluble and membrane TNF-α and inhibits its binding to TNFRs | CD, RA | CD: initial: 400 mg SC (two 200-mg injections) at weeks 0, 2, and 4 |
| Maintenance: 400 mg Q4W | ||||
| RA: initial: 400 mg SC (two 200-mg injections) at weeks 0, 2, and 4 | ||||
| Maintenance: 200 mg Q2W | ||||
| Golimumab (Simponi) | Simponi | Human IgG1 Ab that binds to soluble and membrane TNF-α and inhibits its binding to TNFRs | AS, psoriatic arthritis, RA | 50 mg SC Q4W |
| Alefacept | Amevive | Recombinant human LFA3 ECD and Fc (IgG1) fusion protein that inhibits LFA3–CD2 interaction and blocks lymphocyte activation | Plaque psoriasis | 7.5 mg Q1W IV or 15 mg Q1W IM |
| Efalizumab | Raptiva | Humanized IgG1 that binds CD11a, a subunit of LFA-1 (expressed on all leukocytes), decreases cell surface expression of CD11a and inhibits its binding to ICAM-1, preventing T cell activation, adhesion, and migration to site of inflammation | Plaque psoriasis (withdrawn) | 1 mg/kg Q1W (with 0.7 mg/kg SC first conditioning dose) |
| Natalizumab | Tysabri | Humanized IgG4 that binds to the α4-subunit of α4β1 and α4β7 integrins, blocking their interactions with VCAM1 and MadCAM1 and preventing transmigration of leukocytes into inflamed tissues | CD, relapsing MS | 300 mg IV, Q4W |
| Belimumab | Benlysta | Human IgG1 that binds BLyS, a B cell survival factor, and prevents binding to its receptors on B cells, thereby inhibiting the survival of B cells, (including autoreactive B cells) and differentiation of B cells into Ig-producing plasma cells | SLE | 10 mg/kg IV Q2W for the first 3 doses and Q4W thereafter |
| Ustekinumab | Stelara | Humanized IgG1 directed against p40 subunit of IL-23/IL-12 and prevents interaction between receptors, inhibiting IL-12 and IL-23-mediated immune responses | Plaque psoriasis | 45 or 90 mg (based on body weight) Q4W for the first 2 doses and Q12W SC thereafter |
| Eculizumab | Soliris | Humanized mAb that binds complement protein C5 and inhibits its cleavage to C5a and C5b, preventing the formation of the terminal complement complex and reducing hemolysis | Paroxysmal nocturnal hemoglobinuria | Initial: 600 mg QW IV for 4 weeks, followed by 900 mg IV 1 week later. Maintenance: 900 mg Q2W |
| Tocilizumab | Actemra | Humanized IgG1 directed against soluble and membrane and inhibits IL-6R-mediated signaling through these receptors | JIA, RA | RA: 4 mg/kg or increased to 8 mg/kg (based on clinical experience) IV Q4W |
| JIA: 8 or 12 mg/kg (based on child's body weight) IV Q2W |
IV intravenous; SC subcutaneous; IM intramuscular; PEG polyethylene glycol; IL interleukin; Ig immunoglobulin; R receptor; Fab fragment, antigen binding; Fc fragment, crystallizable; ECD extracellular domain; LFA3 lymphocyte function-associated antigen; TNF tumor necrosis factor α; CTLA4 cytotoxic T lymphocyte antigen 4; BLyS B lymphocyte stimulator; MIU million international units; TIW three times a week; QD daily, QW weekly; QXD every X days; QXW every X weeks; RA rheumatoid arthritis; JIA juvenile idiopathic arthritis; MS multiple sclerosis; SLE systemic lupus erythematosus; CD Chron's disease; UC ulcerative colitis; AS ankylosing spondylitis
aOther indications for the same drug not listed
bDosing regimen is shown for listed indication(s) only. Some drugs are approved in combinations with compounds, which are not specified here. The dosing information is from the package insert