A review of six Phase 3 studies shows that tofacitinib is more effective for rheumatoid arthritis treatment than regimens including placebo and a disease modifying anti-rheumatic drug or methotrexate as monotherapy or in combination therapy.
A review of six Phase 3 studies shows that tofacitinib is more effective for rheumatoid arthritis (RA) treatment than regimens including placebo and a disease modifying anti-rheumatic drug or methotrexate (MTX) as monotherapy or in combination therapy. The efficacy of tofacitinib was similar in patients receiving and not receiving concomitant glucocorticoids (GCs), as these patients had active disease in spite of their background GCs.
The results of the pooled review were presented at the Annual Meeting of American College of Rheumatology meeting in San Francisco this week.
Tofacitinib (marketed under the brand name Xeljanz) is an oral Janus kinase inhibitor currently approved for the treatment of RA. It was developed in a unique public-private partnership between the National Institutes of Health and Pfizer. The drug, though it comes with some significant safety concerns and a box warning about possible injury and death due to infections and other adverse events, may have potential for not only RA treatment but for some dermatologic conditions as well.
Patients with RA often receive concomitant treatment with glucocorticoids (GCs) to control inflammatory symptoms. The purpose of the review was to determine whether the presence or absence of oral GCs has an effect on the efficacy of tofacitinib as monotherapy or in combination with nonbiologic DMARDs.
Tofacitinib efficacy data were analyzed from six Phase 3 studies. Data were pooled from four studies in which patients with inadequate response (IR) to MTX, biologic/ nonbiologic DMARDs, or TNF inhibitors (TNFi) received tofacitinib in combination with MTX or other nonbiologic DMARDs.
Data from two P3 tofacitinib monotherapy studies, ORAL Solo (in DMARD-IR patients) and ORAL Start (in MTX-naïve patients), were analyzed separately. In the P3 tofacitinib clinical program, patients receiving GCs (≤10 mg/day of prednisone or equivalent) prior to enrollment were required to remain on a stable dose throughout the study.
In total, 3,200 tofacitinib-treated patients were included in the analysis. The results show that 279 (57%) and 354 (46%) tofacitinib-treated patients in the P3 monotherapy studies ORAL Solo and ORAL Start were using concomitant GCs, respectively, as were 1,129 (58%) tofacitinib-treated patients in the pooled P3 combination studies. Within each study, baseline demography and disease characteristics were similar regardless of concomitant GC use.
Tofacitinib-treated patients had significantly greater treatment responses compared with the comparator arms for almost all efficacy endpoints. Similar responses were observed with tofacitinib regardless of concomitant GC use.
The researchers would like to see a randomized clinical trial in GC-naïve patients with RA to determine the effect of the addition of GCs on the efficacy of tofacitinib.