Background/Purpose:

Tofacitinib is a novel, oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. Here, we describe the efficacy and safety for adalimumab (ADA) patients (pts) transitioning to tofacitinib open-label extension (OLE) without washout. These data were presented previously.¹

Methods:

In the Phase 3 randomized controlled trial (RCT, NCT00853385) ORAL Standard, pts on background methotrexate received tofacitinib 5 mg twice daily (BID), tofacitinib 10 mg BID, ADA 40 mg subcutaneous injections (every other week [Q2 Wk]), placebo (PBO) advanced to tofacitinib 5 mg BID, or PBO advanced to tofacitinib 10 mg BID (4:4:4:1:1). Primary results were reported.² Eligible pts from the RCT were permitted to enroll in an OLE receiving tofacitinib 10 mg BID without washout (last RCT ADA dose to first OLE tofacitinib dose ≤1 Wk). In this post-hoc analysis, results are described for ADA pts 4.5 months (Mo) before and at end of the RCT, and 4.5 Mo after transition to tofacitinib in OLE. Data for tofacitinib 10 mg BID during RCT and OLE are shown at the same time points.

Results:

145/204 pts randomized to ADA were eligible and enrolled in OLE; 125 started tofacitinib without washout. There were 8 (6.4%) discontinuations during the first 4.5 Mo of OLE (3 drug-related adverse event [AE], 1 unrelated AE, 1 pregnancy, 1 death, 2 other reasons). 148/201 pts randomized to tofacitinib 10 mg BID were eligible and enrolled in OLE; 124 took their first dose of tofacitinib in the OLE ≤1 Wk after their last dose of tofacitinib in the RCT. There were 9 discontinuations in the first 4.5 Mo of OLE (1 drug-related AE, 2 unrelated AE, 6 other reasons). American College of Rheumatology (ACR)20 response rate in ADA to tofacitinib pts (N=124) was 74.2% at 4.5 Mo before end of RCT, 76.6% at end of RCT, and 90.5% at 4.5 Mo after transition to tofacitinib. ACR50 response rates (44.4%, 50.8%, 65.5%) and ACR70 response rates (16.1%, 21.0%, 36.2%) at the same time points showed a similar pattern. Mean change from baseline in health assessment questionnaire‑disability index (HAQ-DI) was -0.55, -0.60, and -0.70 at the same time points. Results in tofacitinib to tofacitinib pts were similar at the same time points and showed a similar pattern of increases from RCT to OLE.

Conclusion:

Changing directly from ADA in RCT to tofacitinib in OLE resulted in sustained clinical response, with numerical improvements in ACR 20, 50, and 70 response rates and mean change in HAQ-DI from baseline. Safety-related events appeared to increase post-transition from ADA to tofacitinib; however, similar increases were seen in tofacitinib-treated pts in the RCT after they transitioned to OLE tofacitinib. The increase in safety-related events in both groups suggests that the increase was not simply the result of overlapping immunomodulatory effects of ADA and tofacitinib.

Table

	ADA to Tofacitinib (N=125)		Tofacitinib to Tofacitinib (N=124)
	Last 4.5 Mo, RCT	First 4.5 Mo, OLE	Last 4.5 Mo, RCT	First 4.5 Mo, OLE
Discontinuations due to AEs, pts (%)	Not applicable	4 (3.2)	Not applicable	3 (2.4)
Serious AEs, pts (%)	1 (0.8)	9 (7.2)	4 (3.2)	9 (7.3)
Serious infection, pts (%)	0 (0)	3 (2.4)	1 (0.8)	3 (2.4)
ADA, adalimumab; AE, adverse event; Mo, month; OLE, open label extension; RCT, randomized controlled trial References: Genovese et al. Ann Rheum Dis 2013; 72: 65. van Vollenhoven et al. N Engl J Med 2012; 367: 508-519.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/tofacitinib-an-oral-janus-kinase-inhibitor-in-a-rheumatoid-arthritis-open-label-extension-study-following-adalimumab-therapy-in-a-phase-3-randomised-clinical-trial/