Efficacy and Safety of Tofacitinib in Chinese Patients with Rheumatoid Arthritis

Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis(RA). This study assessed the efficacy and safety of tofacitinib in Chinese patients with RA enrolled in Phase 3 and long?term extension(LTE) studies.Methods: ORAL Sync was a 1?year, randomized, placebo?controlled, Phase 3 trial. Patients received tofacitinib 5 or 10 mg twice daily(BID) or placebo advanced to tofacitinib 5 or 10 mg BID at 3 or 6 months. All patients remained on ≥1 background conventional synthetic disease?modifying antirheumatic drug. ORAL Sequel is an open?label LTE study(data?cut: March 2015; data collection and analyses were ongoing, and study database was not locked at the time of analysis; study was closed in 2017). Efficacy outcomes: American College of Rheumatology(ACR) 20/50/70 response rates and Disease Activity Score in 28 joints using erythrocyte sedimentation rate(DAS28?4 [ESR]). Patient? and physician?reported outcomes: Health Assessment Questionnaire?Disability Index(HAQ?DI), Patient and Physician Global Assessment of Arthritis, and pain(visual analog scale). Safety was assessed throughout.Results: ORAL Sync included 218 patients; 192 were subsequently enrolled into ORAL Sequel. In ORAL Sync, more patients achieved ACR20(tofacitinib 5 mg BID, 67.4%; 10 mg BID, 70.6%; placebo, 34.1%) and DAS28?4(ESR) <2.6(tofacitinib 5 mg BID, 7.1%;10 mg BID, 13.1%; placebo, 2.3%) with tofacitinib versus placebo at Month 6. Mean changes from baseline in HAQ?DI were greater with tofacitinib versus placebo at Month 6. In ORAL Sequel, efficacy was consistent to Month 48. Incidence rates for adverse events of special interest in tofacitinib?treated patients were similar to the global population.Conclusions: Tofacitinib significantly reduced signs/symptoms and improved physical function and quality of life in Chinese patients with moderate?to?severely active RA up to Month 48. The safety profile was consistent with the global population.Clinical Trial Identifier: NCT00856544 and NCT00413699.

A double-blind, double-dummy, randomized controlled, multicenter trial of ^(99)Tc-methylene diphosphonate in patients with moderate to severe rheumatoid arthritis

Background:Clinical observational studies revealed that ^(99)Tc-methylene diphosphonate(^(99)Tc-MDP)could reduce joint pain and swollenness in rheumatoid arthritis(RA)patients.This multicenter,randomized,double-blind,double-dummy study aimed to evaluate the effects of ^(99)Tc-MDP plus methotrexate(MTX)vs.MTX alone or ^(99)Tc-MDP alone on disease activity and structural damage in MTX-naïve Chinese patients with moderate to severe RA.Methods:Eligible patients with moderate to severely active RA were randomized to receive ^(99)Tc-MDP plus MTX(n=59)vs.MTX(n=59)alone or ^(99)Tc-MDP(n=59)alone for 48 weeks from six study sites across four provinces in China.The primary outcomes were the American College of Rheumatology 20%improvement(ACR20)response rates at week 24 and changes in modified total Sharp score at week 48.Results:At week 24,the proportion of participants achieving ACR20 was significantly higher in the MTX+^(99)Tc-MDP combination group(69.5%)than that in the MTX group(50.8%)or ^(99)Tc-MDP group(47.5%)(P=0.03 for MTX+^(99)Tc-MDP vs.MTX,and MTX+^(99)Tc-MDP vs.^(99)Tc-MDP,respectively).The participants in the MTX+^(99)Tc-MDP group and the ^(99)Tc-MDP group had significantly less important radiographic progression than the participants in the MTX group over the 48 weeks(MTX+^(99)Tc-MDP vs.MTX:P=0.03,^(99)Tc-MDP vs.MTX:P=0.03,respectively).There was no significant difference in terms of adverse events(AEs)among the groups.No serious AEs were observed.Conclusions:This study demonstrated that the combination of ^(99)Tc-MDP with MTX inhibited structural damage and improved disease activity in RA patients compared with MTX and ^(99)Tc-MDP monotherapies,without increasing the rate of AEs.Additional clinical studies of ^(99)Tc-MDP therapy in patients with RA are warranted.Trial Registration:Chictr.org,ChiCTR-IPR-14005684;http://www.chictr.org.cn/showproj.aspx?proj=10088.