Regulatory Decision Summary for Xeljanz XR

The studies provided adequately demonstrated that the safety and efficacy of Xeljanz XR 11 mg is comparable to Xeljanz 5 mg BID in patients with RA. This was based on exposures and maximal concentrations between the two formulations satisfying the criteria for bioequivalence and on predicted efficacy according to exposure-response analyses.

The efficacy endpoints used in the exposure-response analysis were American College of Rheumatology (ACR) response rates showing 20% (20), 50% (50) and 70% (70) improvement, and Disease Activity Scores defined using 28 joint counts and C-reactive protein [DAS28-3 (CRP)]. The predicted DAS 28-3 (CRP) endpoint by exposure-response analysis for Xeljanz XR 11 mg QD was found to be 3.22 and the predicted ACR 20, 50 and 70 response rates for Xeljanz XR 11 mg QD at week 12 were found to be 76%, 48% and 23%. These were comparable to those of Xeljanz 5 mg BID. The exposure-response analysis of ACR response rates and DAS28-3 (CRP) also demonstrated that Cav (or AUC) is the most relevant parameter for predicting the efficacy of tofacitinib.

No serious adverse events or new adverse events were observed with the Xeljanz XR in healthy volunteers in the clinical studies and the review of safety summary. Caution is recommended with the use of Xeljanz XR in patients with pre-existing gastrointestinal narrowing due to the non-deformable nature of the extended release formulation. Based on the demonstration of bioequivalence, the safety information such as Contraindications, Warnings and Precautions observed with Xeljanz is likewise applicable to Xeljanz XR.

Xeljanz XR is generally intended for the same patient subpopulations as Xeljanz, except for patients requiring dose adjustment due to renal or hepatic impairment or to drug interactions. Xeljanz XR is not recommended in patients with moderate to severe hepatic impairment, moderate and severe renal impairment including ESRD patients with dialysis. Xeljanz XR is not recommended when co-administered with CYP3A inhibitors (e.g. ketoconazole), CYP3A and CYP2C19 inhibitors (e.g. fluconazole), immunosuppressants (e.g. tacrolimus and cyclosporine. Co-administration of potent inducers of CYP3A4 (e.g. rifampin) with Xeljanz XR may result in loss of efficacy or reduced clinical response, and is therefore not recommended.

The overall benefit-harm-uncertainty profile of Xeljanz XR is considered favourable.