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Publications

Journal Article Randomized Controlled Trial Ppublish

PubMed: 42760593 DOI: 10.1111/1756-185x.70877

Efficacy and Safety of Tofacitinib Versus Placebo in Patients With Early-Grade Knee Osteoarthritis: A Randomized, Double-Blind, Placebo-Controlled Trial.

Int J Rheum Dis 29(9):e70877

Authors: Rini Fasni, Sujit Kumar Tripathy, Archana Mishra, Shahnawaz Khan, Rachita Meher, Jagat Panda, Debasish Hota, Anand Srinivasan

Affiliations

  • Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, Odisha, India.
  • Department of Orthopedics, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, Odisha, India.

Abstract

AIM

Knee osteoarthritis causes major pain and disability, yet disease-modifying drugs remain limited. Tofacitinib, an oral Janus kinase (JAK) inhibitor, suppresses pro-inflammatory cytokine signaling implicated in osteoarthritis but is unexplored in the knee; we evaluated it versus placebo in early-grade disease.

METHODS

In this single-center, randomized, double-blind, placebo-controlled trial, 100 patients with Kellgren-Lawrence Grades 1 and 2 knee osteoarthritis were randomized to tofacitinib 11 mg extended-release once daily (n = 49) or placebo (n = 51) for 12 weeks. The primary outcome was change in VAS pain to Week 12; secondary outcomes were WOMAC, Oxford Knee Score, EQ-5D-5L, and analgesic use, assessed to Week 12 and a Month-6 follow-up, and analyzed by intention-to-treat with a mixed model for repeated measures.

RESULTS

Baseline characteristics were balanced. Both groups improved within-group during treatment (p < 0.001), but between-group differences were not significant; the Week-12 VAS effect (tofacitinib minus placebo) was +0.02 (95% CI -0.84 to 0.89), with WOMAC, Oxford Knee Score, and EQ-5D-5L likewise excluding their minimal clinically important differences. Improvements rebounded toward baseline by Month 6. Drug-related adverse events were more frequent with tofacitinib (14.3% vs. 0%, p = 0.005) but were gastrointestinal and self-limiting.

CONCLUSION

Tofacitinib was not superior to placebo in early-grade knee osteoarthritis, and the large within-group improvement rebounded toward baseline by 6 months, consistent with a predominantly non-specific (contextual) response. Because participants were selected radiographically without inflammatory phenotyping, these findings do not support tofacitinib in unselected early-grade disease but cannot exclude benefit in an inflammatory phenotype; future trials should stratify accordingly, with longer follow-up and structural outcomes.

TRIAL REGISTRATION

Clinical Trials Registry of India: CTRI/2025/07/090567.

MeSH

Quality Of Life, Safety, Osteoarthritis, Knee, Pain, Pharmaceutical Preparations, Osteoarthritis, Visual Analog Scale