Last reviewed 2026-04-21 · How we verify

Adalimumab with methotrexate

Adalimumab blocks TNF-alpha to reduce inflammation, while methotrexate inhibits dihydrofolate reductase and suppresses immune cell proliferation, together providing synergistic anti-inflammatory and immunosuppressive effects.

Adalimumab blocks TNF-alpha to reduce inflammation, while methotrexate inhibits dihydrofolate reductase and suppresses immune cell proliferation, together providing synergistic anti-inflammatory and immunosuppressive effects. Used for Rheumatoid arthritis, Polyarticular juvenile idiopathic arthritis, Ankylosing spondylitis.

At a glance

Mechanism of action

Adalimumab is a TNF-alpha inhibitor that binds and neutralizes tumor necrosis factor-alpha, a key inflammatory cytokine. Methotrexate is a disease-modifying antirheumatic drug (DMARD) that inhibits folate metabolism and reduces proliferation of activated immune cells. The combination enhances efficacy in suppressing pathogenic immune responses compared to either agent alone.

Approved indications

• Rheumatoid arthritis
• Polyarticular juvenile idiopathic arthritis
• Ankylosing spondylitis
• Crohn's disease
• Ulcerative colitis
• Psoriasis
• Psoriatic arthritis

Common side effects

• Injection site reactions
• Upper respiratory tract infections
• Headache
• Nausea
• Serious infections
• Tuberculosis reactivation
• Malignancy risk

Key clinical trials

• Early Adalimumab Induction for Immune Checkpoint Inhibitor Associated Inflammatory Arthritis (PHASE2)
• Apremilast and Adalimumab in Psoriatic Arthritis Patients (NA)
• An Open-Label Study of Effectiveness of Immunomodulatory Medications for Patients With Relapsing Polychondritis (PHASE2)
• Determination of the Optimal Treatment Target in Ulcerative Colitis (PHASE4)
• Study to Assess Change in Disease Activity and Adverse Events of Oral Upadacitinib Compared to Subcutaneous Adalimumab in Adult Participants With Moderate to Severe Rheumatoid Arthritis (PHASE3)
• Design and Evaluation of an Individualized Biodrug Tapering Strategy Based on Biodrug Dosage: the MONITORA Study (PHASE4)
• Severe Psoriatic Arthritis - Early intervEntion to Control Disease: the SPEED Trial (PHASE4)
• Multicenter Randomized Double Blind Controlled-study to Assess the Potential of Methotrexate Versus Placebo to Improve and Maintain Response to Anti TNF- Alpha Agents in Adult Patients With Moderate to Severe Psoriasis (PHASE4)

Primary sources

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