Session Information
Session Title: ACR Late-Breaking Abstract Poster Session
Session Type: Late-Breaking Abstracts
Background/Purpose: Tofacitinib is a novel, oral Janus kinase inhibitor for the treatment of RA. This Phase 3, 24-mo study (ORAL Start; NCT01039688) compared efficacy, including inhibition of structural damage, and safety of tofacitinib monotherapy vs methotrexate (MTX) in MTX-naïve patients (pts) with active RA. Primary efficacy endpoints (Mo 6) for tofacitinib vs MTX of mean changes from baseline (BL) in van der Heijde modified Total Sharp Score (mTSS) and ACR70 response have been presented.1 Results here are from final analyses (24‑mo).
Methods: Pts were randomized 2:2:1 to tofacitinib 5 mg twice daily (BID), 10 mg BID, or MTX 10 mg/wk with 5 mg/wk increments every 4 wks to 20 mg/wk (mean MTX dose at end of titration [Mo 3], 18.5 mg/wk). Safety and tolerability were also evaluated.
Results: 956 pts received tofacitinib 5 mg BID (N=373), 10 mg BID (N=397), or MTX (N=186). Demographic and BL RA disease characteristics, including radiographic scores, were similar across groups.1 Mean changes from BL in mTSS and ACR20/50/70 response rates were statistically superior for both doses of tofacitinib vs MTX at all time points when measured (ACR20/50/70, first post-BL visit at Mo 1; mTSS, first post-BL visit at Mo 6) through Mo 24 (Table). Erosion and joint space narrowing scores, and HAQ-DI and DAS28‑4[ESR] scores, were also significantly different for tofacitinib vs MTX at all time points measured through Mo 24 (Table).
Incidences of adverse events (AEs), serious AEs, serious infections, and discontinuations due to AEs were similar across groups (Table). Most AEs were mild or moderate; most frequent AE in all groups was infection. Herpes zoster occurred in 3.5%, 4.5%, and 1.1% of tofacitinib 5 mg BID, 10 mg BID, and MTX pts, respectively. Six confirmed malignancies were reported: tofacitinib 5 mg BID (non-Hodgkin’s lymphoma and chronic lymphocytic leukemia); 10 mg BID (prostate cancer, Burkitt’s B-cell lymphoma, colon cancer); and MTX (gastric cancer). An adrenal adenoma with cellular atypia, which the local pathologist was uncertain whether malignant or benign, was also reported in a patient receiving tofacitinib 5 mg BID. Four deaths occurred: tofacitinib 5 mg BID (non-Hodgkin’s lymphoma [post-study], cardiac failure [post-study], sudden cardiac death) and 10 mg BID (colon cancer). At Mo 24, changes in laboratory parameters (neutrophils, lymphocytes, serum creatinine, LDL, and HDL) relative to BL were numerically higher for tofacitinib compared to MTX; liver enzyme elevations were more frequent with MTX (Table).
Conclusion: Tofacitinib monotherapy in MTX-naïve pts demonstrated significant, durable, and clinically meaningful improvements in RA signs and symptoms and physical functioning, and inhibition of progression of structural damage, vs MTX over 24 mo. Safety was similar to that reported in other tofacitinib Phase 3 trials.
- Lee EB, et al. Arthritis Rheum. 2012;64:S1049, Abst 2486.