Biologic Overview
Sara Treat
Background
- "-cept" refers to fusion of a receptor to the Fc part of human immunoglobulin G1 (IgG1)
- "-mab" indicates a monoclonal antibody (mAb)
- "-ximab" indicates a chimeric mAb
- "-zumab" indicates a humanized mAb
- "-umab" indicates a fully human mAb
- “-tinib” indicates a tyrosine kinase inhibitor (small molecule inhibitors, not true biologics)
Safety & Monitoring
- Screening prior to initiation varies based on specific agent, discuss with rheumatology. Consider latent TB (via IGRA), Hep B/C, HIV, age-appropriate cancer screening, pregnancy
- Labs monitoring: CBC (for cytopenias, particularly with MTX, JAKi, IL-6i), LFTs (for hepatotoxicity, particularly with MTX, leflunomide, TNFi), Cr (especially with MTX and JAKi), lipid panel (for hypercholesterolemia, especially with JAKi and IL-6i) every 3 months minimum (depending on agent and disease)
- Avoid live vaccines; use 2022 ACR guidelines for vaccinations in patients with rheumatic and MSK disease. Administer vaccines prior to initiation when possible
B-cell depletion and inhibition
Generic Name (Brand Name) | Mechanism of Action | Common Uses | Common Side Effects |
|---|---|---|---|
| Belimumab (Benlysta) | IgG1-lambda mAb that prevents survival of Blymphocytes by blocking the binding of soluble human B lymphocyte stimulator protein (BLyS) to receptors on B lymphocytes | lupus nephritis, SLE | GI symptoms, hypersensitivity reaction, infections, psychiatric disturbances |
| Rituximab (Rituxan) and Inebilizumab (Uplinza) | mAb against CD20 antigen on surface of B-cells; B cell depletion via abdependent cellmediated cytotoxicity function of NK cells | CLL, Non-Hodgkin lymphomas, GPA, microscopic polyangiitis, pemphigus vulgaris, RA; many off-label uses(GvHD, lupus nephritis, MG, neuromyelitis optica). Inebelizumab is specifically approved for IgG4-RD. | Hypogammaglobulinemia, (may be persistent), infusion reaction, HTN, peripheral edema, night sweats, fever, weight gain, Angioedema, arthralgias, ↑ ALT, hypophosphatemia, hematologic abnormalities |
Complement-inhibition
Generic Name (Brand Name) | Mechanism of Action | Common Uses | Common Side Effects |
|---|---|---|---|
| Avacopan (Tavneos) | Complement 5a receptor antagonist | ANCA vasculitis | HTN, HA, rash, GI upset/ diarrhea, hepatoxicity |
| Eculizumab (Soliris) and Ravulizumab (Ultomiris) | mAb against C5, preventing cleavage to C5a and C5b | aHUS, PNH, myasthenia gravis, neuromyelitis optica; off-label lupus nephritis, catastrophic APS, transplant-related TMA | Infection (particularly encapsulated organisms), HA, HTN, infusion reactions |
Costimulation blockade
Generic Name (Brand Name) | Mechanism of Action | Common Uses | Common Side Effects |
|---|---|---|---|
| Abatacept (Orencia) | inhibits T-cell activation by binding CD80 and CD86 on APCs, thus blocking the required CD28 ixn between APCs and T cells. | RA, psoriasis, JIA | nausea, UTI, HA, URI, Ab development |
Interleukin inhibition
Type of IL inhibition |
Generic Name (Brand Name) |
Mechanism of Action |
Common Uses |
Common Side Effects |
|---|---|---|---|---|
| IL-1 | Anakinra (Kineret) | IL-1 receptor antagonist | IL-1 receptor antagonist deficiency, gout flares, FMF, HLH, Adult-onset Still’s disease (AOSD), sJIA, refractory RA | HA, vomiting, infections, nasopharyngitis, Ab development; in RA: eosinophilia, decreased WBC |
| IL-1 | Canakinumab (Ilaris) | mAb against IL-1β | AOSD, sJIA, Cryoporinassociated periodic syndromes (CAPS), FMF, hyperimmunoglobin D syndrome, TRAPS; off-label: gout flare | weight gain, GI sx, HA, vertigo, serious infections |
| IL-1 | Rilonacept (Arcalyst) | IL- β soluble decoy receptor | Cryoporinassociated periodic syndrome, deficiency IL-1 receptor antagonist, pericarditis | Ab development, infection (including serious infection), local site reaction, URI |
| IL-5 | Mepolizumab (Nucala) | mAb against IL-5, direct IL-5 antagonist | Eosinophilic asthma, EGPA, hypereosinophilic syndromes, rhinosinusitis with nasal polyps | local injection site reaction, HA |
| IL-6 | Tocilizumab (Actemra) | IL-6 receptor antagonist | GCA, RA, JIA, neuromyelitis optica, systemic sclerosis, ILD, cytokine release syndrome for CAR T cells | ↑ serum cholesterol, ↑ AST/ALT, infusion rxn, HSV infection(<2%) |
| IL-6 | Sarilumab (Kevzara) | IL-6 receptor antagonist (soluble + membranebound) | RA | ↑ AST/ALT, HSV infection(<2%) |
| IL-23 | Guselkumab (Tremfya) | human IgG1 mAb against IL-23 | PsA, psoriasis | URI, tinea, GI sx |
| IL-23 | Risankizumab (Skyrizi) | mAb against IL-23 via p19 | IBD, PsA, psoriasis, JIA | nausea, UTI, HA, URI, Ab development |
| IL-12/23 | Ustekinumab (Stelara) | mAb against IL-12 + IL-23 | IBD, psoriasis | nasopharyngitis, Ab development, acne vulgaris, GI sx, GU sx |
| IL-17 | Brodalumab (Siliq) | human IgG1 mAb against IL-17A | Psoriasis | infection, tinea, GI, suicidal ideation and behavior (REMS program) |
| IL-17 | Ixekizumab (Taltz) | human IgG4 mAb against IL-17A | AS, PsA, psoriasis | infection, tinea, neutropenia, Ab development, URI, Crohn’s (<1%) |
| IL-17 | Secukinumab (Cosentyx) | human IgG1 mAb against IL-17A | AS, psoriasis | nasopharyngitis, GI, IBD (<1%) |
| IL-17 | Bimekizumab (Bimzelx) | Humanized IgG1 mAb against IL-17A and IL-17F | Psoriasis, PsA, axial spondyloarthritis | URI, fungal infections, HA, GI |
Kinase inhibition
BLACK BOX warning for mortality, increased malignancies, thrombosis (DVT and PE), and increased cardiovascular events. Data is from tofacitinib, but warning is applied to all JAK inhibitors.
Generic Name (Brand Name) |
Mechanism of Action |
Common Uses |
Common Side Effects |
|---|---|---|---|
| Abrocitinib (Cibinqo) | JAK-1 inhibitor | Atopic dermatitis | nausea, infections, nasopharyngitis |
| Baracitinib (Olumiant) | JAK-1 and JAK-2 inhibitor | RA, alopecia areata, off-label: COVID-19 | URI, nausea, ÝAST/ALT; <1% lymphoma |
| Ruxolitinib (Jakafi) | JAK-1 and JAK-2 inhibitor | Topical: atopic dermatitis and vitiligo Oral: GvHD, polycythemia vera, myelofibrosis | HTN, HLD, GI upset, ↑ LFTs, anemia, infection, dizziness, muscle spasm, fever |
| Tofacitinib (Xeljanz) | JAK-1 and JAK-3 inhibitor | RA, UC, JIA, psoriatic arthritis | nasopharyngitis, skin rash, GI sx, GU sx; <1% lymphoma |
| Upadacitinib (Rinvoq) | Non-specific JAK inhibitor | RA | URI, nausea, neutropenia, ↑AST, ↑CPK |
TNF inhibition
Generic Name (Brand Name) |
Mechanism of Action |
Common Uses |
Common Side Effects |
|---|---|---|---|
| Adalilumab (Humira) | mAb against TNFα | RA, IBD, AS, psoriasis, uveitis, hidradenitis suppurativa | infection (esp mycobacterial and fungal), drug induced lupus, skin rash, HA, URI, ↑ CPK, +ANA titer (12%), Ab development (3-26%) |
| Certolizumab (Cimzia) | humanized mAb Fab fragment against TNFα | RA, Crohn’s, AS, psoriasis; | skin rash, nausea, URI |
| Etanercept (Enbrel) | TNF receptor linked to Fc portion of IgG1 binds TNF | RA, AS, psoriasis, JIA | skin rash, diarrhea, +ANA titer (11%) |
| Golimumab (Simponi) | mAb against TNFα | RA, UC, AS, psoriasis, JIA | URI, Ab development (16-38%), +ANA titer (4-17%) |
| Infliximab (Remicade) | chimeric mAb against TNFα | RA, IBD, AS, psoriasis | abd pain, URI sx, anemia, ↑ ALT, Ab development (10-50%) |