Tofacitinib (CP-690,550) in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors: a randomised phase 3 trial

Evaluation of the Effect of Tofacitinib Exposure on Outcomes in Kidney Transplant Patients

“…meaningfully between the two tofacitinib treatment armsmost likely reflecting the overlapping pharmacokinetic exposures within the dose range studied. The high event frequencies of PTLD and serious infections reported in the fixed-dose tofacitinib treatment groups in this Phase 2b transplant study were contrary to the findings in patients with rheumatoid arthritis (3)(4)(5)(6)(7)(8), which is likely attributable to differences in patient populations and the more intense and complex combination immunosuppressive regimens received by transplant patients.…”

“…Cytokine signaling through the JAK pathway is integral to lymphocyte activation, proliferation and function; thus, inhibition of JAK3 and/or JAK1 results in suppression of multiple aspects of the immune response (1,2). The efficacy of tofacitinib for the treatment of moderate to severe rheumatoid arthritis has been demonstrated in many studies (3)(4)(5)(6)(7)(8). Tofacitinib is also being developed for the treatment of other autoimmune disorders such as psoriasis (9) and inflammatory bowel disease (10).…”

Tofacitinib With Methotrexate in Third‐Line Treatment of Patients With Active Rheumatoid Arthritis: Patient‐Reported Outcomes From a Phase III Trial

“…Six phase III RCTs have demonstrated significant improvements in signs and symptoms of active RA compared with placebo (17)(18)(19)(20)(21) or MTX (22). PROs have been reported from all 6 phase III trials, and they have demonstrated significant improvements with tofacitinib treatment versus placebo, with and without background MTX, across a range of patient populations (23)(24)(25)(26)(27)(28).…”

“…Patients randomized to receive placebo advanced to tofacitinib 5 mg or 10 mg twice daily at month 3 (17). Co-primary end points, including ACR criteria for 20% improvement in disease activity (ACR20) response, mean change from baseline in Health Assessment Questionnaire (HAQ) disability index (DI) score, and 4-variable Disease Activity Score in 28 joints (DAS28)-defined remission (using erythrocyte sedimentation rate [ESR] Ͻ2.6 mm/hour), all measured at month 3, were met for both doses of tofacitinib (17). Here, we report improvements in additional PROs with tofacitinib (versus placebo) from this phase III RCT.…”

Tofacitinib: a janus kinase inhibitor for rheumatoid arthritis

“…In ORAL Step, in patients who had not previously responded after treatment with a TNF inhibitor, tofacitinib plus methotrexate increased the threemonth ACR20 response rate to 42% (vs 24% with methotrexate plus placebo; p=0.002) and significantly reduced disability and disease activity scores. 10 In ORAL Start, 11 tofacitinib was superior to methotrexate in treatment-naïve patients, about 40% of whom had previously been treated with a conventional DMARD other than methotrexate (eg leflunomide, sulfasalazine), with significantly greater ACR20 response rates and reductions in disease activity and disability scores at 6, 12 and 24 months. 11 Tofacitinib also slowed disease progression more than methotrexate.…”