March 2025

RHEUMATOLOGY

JAK INHIBITORS VS. BIOLOGIC DISEASE-MODIFYING ANTIRHEUMATIC DRUGS FOR RA PAIN

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Despite disease modifying antirheumatic drug (DMARD) therapy, pain continues to be a problem for many patients with rheumatoid arthritis (RA). Recognizing the unmet need for effective pain relief in RA, Yvonne C. Lee, MD, shares insights on the use of JAK inhibitors versus biologic disease-modifying DMARDs in managing RA pain.

Key Takeaways
  • Pain management remains a critical challenge for RA patients, often requiring more than just anti-inflammatory treatments.
  • Janus Kinase (JAK) inhibitors show promise for pain management in RA, with potential short-term advantages over tumor necrosis factor (TNF) inhibitors, particularly in patients with prior DMARD treatments.
  • There is a need for precision-based medicine approaches to manage pain, including a comprehensive approach to assessment and management.

Treatment With DMARDs
  • DMARDs provide modest improvements in pain, but many patients continue to have pain that interferes with their daily activities.
  • Many patients resort to long-term opioid use despite its ineffectiveness for chronic pain and associated safety risks.

Emerging Role of JAK Inhibitors
  • Preclinical studies indicate the involvement of the JAK-STAT3 pathway in pain signaling at both the joint and central nervous system levels.
  • Phase 3 trials suggest that JAK inhibitors may be more effective in reducing pain than TNF inhibitors. Patients randomized to receive baricitinib or upadacitinib (JAK inhibitors) reported less intense joint pain than patients who received adalimumab (a TNF inhibitor).

JAK Inhibitors vs. DMARDs
  • A study using data from Swedish national registries found that:
    • JAK inhibitors resulted in slightly greater reductions in pain compared to TNF inhibitors at three months.
    • At 12 months, a higher proportion of patients taking JAK inhibitors remained on the drug and achieved low pain levels compared to those taking TNF inhibitors, though the difference was not statistically significant.
    • Patients who had previously received at least two DMARDs had greater pain reduction.

Recommendations for Clinicians
  • Assess the underlying mechanisms contributing to pain in individual patients, including inflammatory, neuropathic and nociplastic pain contributions.
  • Consider JAK inhibitors for patients with RA who have tried at least two other DMARDs and do not have other contraindications to these medications.
  • Use a multidisciplinary approach to pain management that may include physical therapy, occupational therapy and psychological support​.
Yvonne C. Lee, MD, Helen Myers McLoraine Professor of Rheumatology and Associate Professor of Rheumatology and Epidemiology at Northwestern Medicine

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