What are the current treatment options for rheumatoid arthritis, including new medications?

Current Treatment Options for Rheumatoid Arthritis

Yes, there are several newer medications for rheumatoid arthritis, including JAK inhibitors (tofacitinib, baricitinib) and newer biologic DMARDs (sarilumab, sirukumab, clazakizumab), which have been incorporated into treatment guidelines since 2016-2019. 1

First-Line Treatment Strategy

Methotrexate remains the cornerstone of initial therapy and should be started immediately upon diagnosis. 1, 2, 3

• Start MTX at 25-30 mg weekly (rapid escalation to this dose) with folate supplementation 1, 2
• Add short-term glucocorticoids as bridging therapy until MTX takes effect, then taper within approximately 3 months 1, 2
• If MTX is contraindicated or not tolerated early, use leflunomide or sulfasalazine as alternatives 1, 2

Treatment Monitoring and Escalation Timeline

• Monitor disease activity every 1-3 months during active disease 1, 2
• Adjust therapy if no improvement by 3 months or target not reached by 6 months 1, 2
• Target sustained remission or low disease activity 1, 2

Second-Line Options: When to Add Biologics or JAK Inhibitors

If first csDMARD strategy fails, the decision depends on prognostic factors: 1, 2

Without Poor Prognostic Factors:

• Switch to another csDMARD (leflunomide, sulfasalazine, hydroxychloroquine) 1

With Poor Prognostic Factors (autoantibodies, high disease activity, early erosions):

• Add a biologic DMARD or JAK inhibitor to the csDMARD 1, 2

Newer Biologic DMARDs Available

The following biologics are recommended by EULAR guidelines: 1

TNF Inhibitors:

• Adalimumab, certolizumab pegol, etanercept, golimumab, infliximab (including biosimilars) 1

Non-TNF Biologics:

• Tocilizumab (IL-6 inhibitor) - FDA approved for moderately to severely active RA 4
• Sarilumab (IL-6 inhibitor) - newer agent added to 2019 guidelines 1
• Abatacept (T-cell costimulation modulator) 1
• Rituximab (anti-CD20) 1

Newer Targeted Synthetic DMARDs (JAK Inhibitors)

JAK inhibitors represent a newer class of oral medications: 1

• Tofacitinib - first JAK inhibitor approved 1, 5
• Baricitinib - added to guidelines in 2017 update 1
• These are considered targeted synthetic DMARDs (tsDMARDs) and can be used after csDMARD failure 1

Combination Therapy Principles

• Biologics and JAK inhibitors should be combined with a csDMARD (typically MTX) for optimal efficacy 1, 2
• IL-6 pathway inhibitors (tocilizumab, sarilumab) and JAK inhibitors may have advantages when csDMARDs cannot be used as comedication 1
• Avoid combining biologic DMARDs with other biologics due to increased infection risk 4

Managing Treatment Failure

If a biologic or JAK inhibitor fails: 1, 2

• Switch to another biologic with a different mechanism of action (preferred) 1
• Alternatively, try a second TNF inhibitor if the first TNF inhibitor failed 1
• Any biologic or JAK inhibitor can be used after failure of another 1

Tapering in Remission

Once persistent remission is achieved: 1, 2

• Taper glucocorticoids first 1
• Consider tapering biologics/JAK inhibitors if combined with csDMARD 1
• Consider tapering csDMARD only if persistent remission maintained 1

Critical Pitfalls to Avoid

• Do not delay DMARD initiation - start immediately upon diagnosis 1, 2
• Do not underdose MTX - escalate rapidly to 25-30 mg weekly 1, 2
• Do not skip glucocorticoid bridging therapy when starting MTX 1, 2
• Do not wait beyond 3 months to adjust therapy if no improvement 1, 2
• Screen for tuberculosis before starting biologics (except in COVID-19 patients) 4
• Monitor CBC and liver function before and during treatment 4

Safety Considerations for Newer Agents

Tocilizumab (IL-6 inhibitor) carries increased infection risk: 4

• Test for latent tuberculosis before initiation (except COVID-19 patients) 4
• Monitor for serious infections including opportunistic infections 4
• Check baseline neutrophil count (>2000/mm³), platelets (>100,000/mm³), and liver enzymes (ALT/AST <1.5x ULN) 4