Background Tofacitinib is an oral JAK inhibitor for the treatment of RA.
Objectives This analysis assessed if patients achieving Clinical Disease Activity Index (CDAI) remission (REM) or low disease activity (LDA) at Month 6 had less radiographic progression and improved patient-reported outcomes (PROs) at Month 24 and compared results between tofacitinib and MTX.
Methods ORAL Start (NCT01039688) and ORAL Scan (NCT00847613) were Phase 3 randomised controlled trials (RCTs) in MTX therapeutically naïve and MTX inadequate response (IR) patients with RA, respectively. In ORAL Start and Scan, patients received tofacitinib 5 or 10 mg twice daily (BID) monotherapy vs MTX monotherapy or tofacitinib 5 or 10 mg BID + MTX vs placebo + MTX, respectively. This was an observed analysis of patients with radiographs at Months 6, 12 and 24, excluding placebo-treated patients in ORAL Scan. Patients were classified according to CDAI responses at Month 6: REM (CDAI ≤2.8); LDA (CDAI >2.8 to ≤10); or incomplete-responders (CDAI >10). Outcomes included the proportion of patients with no radiographic progression (change in modified Total Sharp Score [mTSS] ≤0) and/or HAQ-DI ≤0.5 (defined as normative) at Month 24, and mean changes from baseline in mTSS and HAQ-DI.
Results In ORAL Start, 250, 269 and 98 patients received tofacitinib 5 mg BID, tofacitinib 10 mg BID and MTX, respectively. In ORAL Scan, 193 and 201 patients received tofacitinib 5 and 10 mg BID, respectively. Baseline demographics were generally similar between subpopulations within each RCT; however, incomplete responders generally had higher baseline disease activity. In both ORAL Start and Scan, patients in REM or LDA with tofacitinib at Month 6 were more likely to be radiographic non-progressors and achieve normative HAQ-DI scores at Month 24 (Table). Tofacitinib-treated patients in REM at Month 6 generally had better HAQ-DI scores at Month 24 than LDA patients. In ORAL Start at Month 6, a higher proportion of tofacitinib- than MTX-treated patients were in REM or LDA (Table). CDAI incomplete responders receiving tofacitinib had improved HAQ-DI scores and less radiographic progression compared with MTX-treated counterparts. Overall, more tofacitinib-treated patients who achieved REM or LDA were non-progressors or achieved HAQ-DI scores ≤0.5 compared to those treated with MTX.
Conclusions More MTX-naïve or MTX-IR tofacitinib-treated patients achieving CDAI REM or LDA at Month 6 were radiographic non-progressors or achieved normative HAQ DI scores at Month 24, compared with CDAI incomplete responders. In ORAL Start, more tofacitinib-treated than MTX-treated MTX-naïve patients achieved CDAI REM or LDA at Month 6 with better PROs and radiographic outcomes at Month 24.
Acknowledgement Previously presented (Strand V et al. Arthritis Rheumatol 2015; 67 (S10): Abstr 1633) and reproduced with permission from Arthritis Rheumatol. This study was funded by Pfizer Inc. Editorial support was provided by S Johnson of Complete Medical Communications and funded by Pfizer Inc.
Disclosure of Interest V. Strand Grant/research support from: Pfizer Inc, Consultant for: Pfizer Inc, A. Kavanaugh Grant/research support from: Pfizer Inc, A. Kivitz Grant/research support from: Pfizer Inc, Consultant for: Pfizer Inc, Speakers bureau: Pfizer Inc, D. van der Heijde Consultant for: Pfizer Inc, Employee of: Imaging Rheumatology, K. Kwok Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, E. Akylbekova Consultant for: Pfizer Inc, Employee of: Quintiles Inc, A. Soonasra Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, M. Snyder Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, C. Connell Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, E. Bananis Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, J. Smolen Grant/research support from: Pfizer Inc, Consultant for: Pfizer Inc