Biologic and targeted immunosuppressants
Biologic and targeted synthetic disease-modifying antirheumatic drugs block a single cytokine, receptor, or signaling enzyme and are escalated to after conventional synthetic agents such as methotrexate fail. A tumor necrosis factor inhibitor is generally first-line, chosen by target organ and comorbidity, with mandatory tuberculosis and hepatitis B screening before the first dose.
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What this article covers
- Overview
Definition: biologic and targeted synthetic disease-modifying antirheumatic drugs (DMARD) are parenteral protein-based agents, or oral small molecules for the Janus kinase (JAK) inhibitors, that…
- Epidemiology
Escalation population: used when RA, PsA, ankylosing spondylitis (AS), or systemic lupus erythematosus (SLE) stays active despite conventional synthetic DMARD; only 30% to 50% of patients on…
- Risk factors
Latent or active tuberculosis, chronic hepatitis B, or untreated human immunodeficiency virus (HIV) infection: TNF inhibitors carry the highest tuberculosis reactivation risk and rituximab the…
- Pathophysiology
Tumor necrosis factor blockade: infliximab, adalimumab, certolizumab pegol (a PEGylated Fab' fragment with minimal placental transfer), golimumab, and etanercept all neutralize TNF-alpha, the…
- Clinical features
Reactivation tuberculosis, endemic fungal infection, and hepatitis B reactivation: fever, weight loss, and pulmonary or disseminated disease, most classically with TNF inhibitors, which impair…
- Differential diagnosis
Etanercept versus a monoclonal TNF antibody: both treat RA, PsA, and AS equally, but etanercept fails to neutralize membrane-bound TNF, so it lacks efficacy in inflammatory bowel disease and uveitis, unlike infliximab and adalimumab.
- Diagnosis
First, before any biologic or targeted synthetic agent starts, pre-treatment screening establishes baseline infection and organ-function risk.
- Management
First, confirm inadequate response to an optimized conventional synthetic DMARD, since these agents are escalation therapy outside vasculitis induction and autoinflammatory syndromes.
- Complications
Serious and opportunistic infection: the shared class risk, including tuberculosis and fungal reactivation with TNF inhibitors and hepatitis B reactivation, most severe with rituximab.
- Prognosis
Combining a TNF inhibitor with a conventional synthetic DMARD improves durability: it slows radiographic damage even with persistent clinical activity and limits immunogenicity.
- Prevention
Complete at least 1 month of latent tuberculosis treatment before the first dose: isoniazid plus rifapentine weekly for 3 months, rifampin daily for 4 months, or isoniazid plus rifampin daily for 3…
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Related articles
- Conventional immunosuppressants
Conventional immunosuppressants are the antifolate, antimetabolite, alkylating, and calcineurin-inhibiting agents (methotrexate, hydroxychloroquine, sulfasalazine, leflunomide, azathioprine, mycophenolate mofetil, cyclophosphamide, cyclosporine, tacrolimus) plus systemic glucocorticoids that anchor treatment across rheumatoid arthritis, lupus, and vasculitis. Methotrexate is the first-line conventional synthetic disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis, hydroxychloroquine is background therapy for essentially all lupus, and cyclophosphamide is reserved for organ- or life-threatening disease.
- Rheumatoid arthritis
Rheumatoid arthritis is a chronic systemic autoimmune disease causing symmetric small-joint polyarthritis of the hands and feet that spares the distal interphalangeal joints, with morning stiffness over an hour. Diagnosis combines the ACR/EULAR classification criteria with rheumatoid factor, anti-CCP antibody, and radiographs. Treat-to-target management anchors on methotrexate, escalating to a biologic or targeted synthetic disease-modifying antirheumatic drug when remission is not reached.
- Psoriatic arthritis
Psoriatic arthritis (PsA) is a seronegative spondyloarthritis that develops in up to 30% of patients with psoriasis, producing asymmetric oligoarthritis or distal interphalangeal joint disease, dactylitis, enthesitis, nail dystrophy, and axial involvement. Diagnosis is clinical, supported by the CASPAR criteria. Limited peripheral disease is treated with an NSAID or intra-articular glucocorticoid, more active disease with methotrexate, a tumor necrosis factor inhibitor, or an interleukin-17 inhibitor.
- Ankylosing spondylitis
Ankylosing spondylitis is the radiographic axial spondyloarthritis: a chronic, HLA-B27-associated inflammatory disease of the sacroiliac joints, spine, and entheses presenting with inflammatory back pain before age 45. Sacroiliitis on pelvic radiograph or MRI establishes the diagnosis. First-line treatment is continuous scheduled NSAIDs with active exercise, escalating to a tumor necrosis factor inhibitor, then an interleukin-17 inhibitor, when NSAIDs fail.
- Granulomatosis with polyangiitis
Granulomatosis with polyangiitis (GPA) is an antineutrophil cytoplasmic antibody (ANCA)-associated necrotizing granulomatous vasculitis of the upper airway, lower airway, and kidney, most often with cytoplasmic ANCA (c-ANCA) targeting proteinase 3 (PR3). Diagnosis rests on the clinical triad, ANCA serology, and tissue biopsy showing pauci-immune vasculitis, and treatment begins with high-dose glucocorticoids plus rituximab or cyclophosphamide for organ-threatening disease, followed by rituximab or azathioprine maintenance.
- Tuberculosis
Tuberculosis, caused by Mycobacterium tuberculosis, remains a leading global cause of infectious death and presents as latent infection, primary/secondary pulmonary disease, or extrapulmonary and disseminated (miliary) disease. Diagnosis rests on AFB smear, NAAT, and mycobacterial culture (the gold standard), and drug-susceptible active disease is treated with a four-drug regimen (isoniazid, rifampin, pyrazinamide, ethambutol) for 2 months followed by isoniazid plus rifampin for 4 to 7 months.