Scope and approach
This article outlines evidence‑based pharmacologic strategies for inflammatory arthritis (including rheumatoid arthritis, psoriatic arthritis, and other immune‑mediated arthritides) and summarizes practical safety and monitoring considerations. Non‑inflammatory degenerative arthritis (eg, osteoarthritis) requires different approaches and is not the focus here.
Treatment goals
- Rapid control of inflammation and pain
- Prevention of structural joint damage and functional loss
- Minimization of treatment toxicity
- Preservation of quality of life through combined pharmacologic and non‑pharmacologic measures
Stepwise pharmacologic framework
1) Non‑steroidal anti‑inflammatory drugs (NSAIDs)
NSAIDs (eg, ibuprofen, naproxen, diclofenac, celecoxib, meloxicam) inhibit cyclooxygenase (COX) enzymes to reduce prostaglandin‑mediated pain and inflammation. They provide symptomatic relief but do not alter disease progression in inflammatory arthritides. Choose agents based on efficacy, GI/cardiovascular risk profile, renal function, drug interactions, and patient comorbidities. Use the lowest effective dose for the shortest duration necessary and co‑prescribe gastroprotection for at‑risk patients.
2) Glucocorticoids
Systemic glucocorticoids offer rapid suppression of inflammation and are useful for bridging therapy while disease‑modifying drugs take effect or for controlling severe flares. Use the lowest effective dose and plan a taper to minimize adverse effects (osteoporosis, hyperglycemia, infection risk, adrenal suppression). For localized disease, intra‑articular steroid injections provide effective targeted control with fewer systemic effects.
3) Conventional synthetic disease‑modifying antirheumatic drugs (csDMARDs)
csDMARDs aim to slow or halt structural damage. First‑line agents include:
- Methotrexate (MTX): Anchor drug for many inflammatory arthritides; weekly dosing with folic acid supplementation; monitor CBC, LFTs, and renal function.
- Leflunomide: Alternative or add‑on to MTX; monitor LFTs and consider washout (cholestyramine) if toxicity occurs.
- Sulfasalazine, hydroxychloroquine: Useful in combination regimens and particular phenotypes (eg, mild disease, pregnancy planning: hydroxychloroquine is safe in pregnancy).
4) Biologic DMARDs and targeted synthetic agents
When patients have inadequate response to csDMARDs or have aggressive disease, escalate to targeted therapies:
- TNF inhibitors: (eg, etanercept, infliximab, adalimumab) effective across many arthritides. Screen for latent TB and hepatitis B prior to therapy.
- IL‑6 receptor inhibitors: (eg, tocilizumab) for refractory RA or specific phenotypes; monitor lipids and LFTs.
- B‑cell targeted therapy: (eg, rituximab) for seropositive disease or refractory cases.
- Costimulation blockade: abatacept for certain RA and psoriatic arthritis patients.
- JAK inhibitors (targeted synthetic DMARDs): (eg, tofacitinib, baricitinib, upadacitinib) oral options effective in multiple arthritides; monitor for VTE risk and infections and assess cardiovascular risk per regulatory guidance.
Biologics and JAK inhibitors substantially reduce disease activity and structural progression but increase infection risk and require baseline screening (TB, hepatitis B/C), vaccination update, and ongoing vigilance for opportunistic infections and rare adverse events.
Safety, monitoring, and vaccination
- Baseline evaluation: CBC, renal and liver function, hepatitis B/C serologies, TB screening (IGRA or chest x‑ray), and baseline vaccination status.
- Ongoing monitoring: periodic CBC, LFTs, creatinine, lipid profile (especially with JAK inhibitors and IL‑6 blockade), and targeted organ monitoring as indicated.
- Vaccination: Administer inactivated vaccines (influenza, pneumococcal, hepatitis B) ideally before initiating biologics; avoid live vaccines during significant immunosuppression.
- Infection vigilance: Educate patients to report fevers or signs of infection promptly; hold immunosuppression during serious infections and coordinate with specialists for treatment and re‑initiation plans.
Special considerations
- Pregnancy and fertility: Methotrexate and leflunomide are teratogenic—stop preconception and use alternative therapies (eg, hydroxychloroquine, TNF inhibitors with careful selection). Coordinate care with obstetrics.
- Comorbidities: Tailor therapy for patients with cardiovascular disease, chronic lung disease, or malignancy history—some agents carry specific warnings.
- Surgery: Time biologic dosing around elective procedures to reduce infection risk and coordinate perioperative management.
Non‑pharmacologic measures and rehabilitation
Integrate physical therapy, occupational therapy, weight management, joint protection strategies, and psychosocial support. Early referral for rehabilitation optimizes function and reduces disability.
Practical prescribing tips
- Start disease‑modifying therapy early in inflammatory arthritis—”treat to target” with objective measures (eg, DAS28).
- Use combination csDMARDs or add targeted therapy if targets are unmet.
- Minimize long‑term glucocorticoid exposure; use steroid‑sparing strategies actively.
Conclusion
Arthritis management requires individualized, often combination therapy using NSAIDs and short‑term glucocorticoids for symptom control, csDMARDs to prevent structural damage, and biologic or targeted agents for refractory or aggressive disease. Safety monitoring, vaccination planning, and non‑pharmacologic care are essential to optimize outcomes and minimize harm.
