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)
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 B-lymphocytes 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) |
mAb against CD20 antigen on surface of B-cells; B cell depletion via ab-dependent cell mediated 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) | Hypogammaglobulinemia, (may be persistent), infusion reaction, HTN, peripheral edema, night sweats, fever, weight gain, angioedema, arthralgias, increased 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, hepatotoxicity |
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 interaction between APCs and T cells. | RA, psoriasis, JIA | Nausea, UTI, HA, URI, Antibody development |
IL-1 Inhibition¶
| Generic Name (Brand Name) | Mechanism of Action | Common Uses | Common Side Effects |
|---|---|---|---|
| Anakinra (Kineret) |
IL-1 receptor antagonist | IL-1 receptor antagonist deficiency, gout flares, FMF, HLH | HA, vomiting, infections, nasopharyngitis, Antibody development; in RA: eosinophilia, decreased WBC |
| Canakinumab (Ilaris) |
mAb against IL-1β | Adult onset Still’s disease, Cryoporin-associated periodic syndromes (CAPS), FMF, hyperimmunoglobin D syndrome, TRAPS; off-label: gout flare | Weight gain, GI sx, HA, vertigo, serious infections |
| Rilonacept (Arcalyst) |
IL-β soluble decoy receptor | Cryoporin-associated periodic syndrome, deficiency IL-1 receptor antagonist, pericarditis | Antibody development, infection (including serious infection), local site reaction, URI |
IL-5 Inhibition¶
| Generic Name (Brand Name) | Mechanism of Action | Common Uses | Common Side Effects |
|---|---|---|---|
| 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 Inhibition¶
| Generic Name (Brand Name) | Mechanism of Action | Common Uses | Common Side Effects |
|---|---|---|---|
| Tocilizumab (Actemra) |
IL-6 receptor antagonist | GCA, RA, JIA, neuromyelitis optica, systemic sclerosis, ILD, cytokine release syndrome for CAR T cells | Increased serum cholesterol, increased AST/ALT, infusion reaction, HSV infection (<2%) |
| Sarilumab (Kevzara) |
IL-6 receptor antagonist (soluble + membrane-bound) | RA | Increased AST/ALT, HSV infection (<2%) |
IL-12/23 Inhibition¶
| Generic Name (Brand Name) | Mechanism of Action | Common Uses | Common Side Effects |
|---|---|---|---|
| Guselkumab (Tremfya) |
Human IgG1 mAb against IL-23 | Psoriasis | Upper respiratory tract infection (URI), tinea, gastrointestinal symptoms (GI sx) |
| Risankizumab (Skyrizi) |
mAb against IL-23 via p19 | IBD, psoriasis, JIA | Nausea, urinary tract infection (UTI), headache (HA), URI, Antibody development |
| Ustekinumab (Stelara) |
mAb against IL-12 + IL-23 | IBD, psoriasis | Nasopharyngitis, Antibody development, acne vulgaris, gastrointestinal symptoms (GI sx), genitourinary symptoms (GU sx) |
IL-17 Inhibition¶
| Generic Name (Brand Name) | Mechanism of Action | Common Uses | Common Side Effects |
|---|---|---|---|
| Brodalumab (Siliq) |
Human IgG1 mAb against IL-17A | Psoriasis | Infection, tinea, gastrointestinal (GI) issues, suicidal ideation and behavior (REMS program) |
| Ixekizumab (Taltz) |
Human IgG4 mAb against IL-17A | Ankylosing spondylitis (AS), psoriasis | Infection, tinea, neutropenia, Antibody development, upper respiratory tract infection (URI), Crohn’s disease (<1%) |
| Secukinumab (Cosentyx) |
Human IgG1 mAb against IL-17A | AS, psoriasis | Nasopharyngitis, GI issues, inflammatory bowel disease (IBD) (<1%) |
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 | Upper respiratory tract infection (URI), nausea, increased AST/ALT; less than 1% lymphoma |
| Ruxolitinib (Jakafi) |
JAK-1 and JAK-2 inhibitor | Topical: atopic dermatitis and vitiligo Oral: GvHD, polycythemia vera, myelofibrosis |
Hypertension (HTN), hyperlipidemia (HLD), gastrointestinal (GI) upset, increased liver function tests (LFTs), anemia, infection, dizziness, muscle spasm, fever |
| Tofacitinib (Xeljanz) |
JAK-1 and JAK-3 inhibitor | RA, UC, JIA, psoriatic arthritis | Nasopharyngitis, skin rash, GI symptoms, genitourinary (GU) symptoms; less than 1% lymphoma |
| Upadacitinib (Rinvoq) |
Non-specific JAK inhibitor | RA | Upper respiratory tract infection (URI), nausea, neutropenia, increased AST, increased 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 (especially mycobacterial and fungal), drug-induced lupus, skin rash, headache, upper respiratory tract infection (URI), increased creatine phosphokinase (CPK), positive antinuclear antibody (ANA) titer (12%), Antibody development (3-26%) |
| Certolizumab (Cimzia) |
Humanized mAb Fab fragment against TNFα | RA, Crohn’s, AS, psoriasis; *approved for pregnancy | Skin rash, nausea, URI |
| Etanercept (Enbrel) |
TNF receptor linked to Fc portion of IgG1 binds TNF | RA, AS, psoriasis, JIA | Skin rash, diarrhea, positive ANA titer (11%) |
| Golimumab (Simponi) |
mAb against TNFα | RA, UC, AS, psoriasis, JIA | URI, Antibody development (16-38%), positive ANA titer (4-17%) |
| Infliximab (Remicade) |
Chimeric mAb against TNFα | RA, IBD, AS, psoriasis | Abdominal pain, URI symptoms, anemia, increased ALT, Antibody development (10-50%) |