Tofacitinib useful for treating rheumatoid arthritis in Asians
Treatment with tofacitinib yields significant improvements in signs and symptoms of rheumatoid arthritis (RA) in patients from the Asia Pacific, according to data from a posthoc analysis. The drug has a safety profile consistent with global tofacitinib studies, although infections occur more frequently in Asians.
The posthoc analysis included RA patients in the Asia‐Pacific region treated with tofacitinib 5 mg (n=397) or 10 mg (n=382), twice daily with or without conventional synthetic disease‐modifying antirheumatic drugs, or placebo (n=243) in phase I–III and long‐term extension (LTE) studies. Efficacy was assessed over 24 months, and safety over 92 months.
At month 3, tofacitinib produced significant improvements in RA signs and symptoms, as well as in physical function (measured using the Health Assessment Questionnaire‐Disability Index [HAQ-DI]), compared with placebo. All improvements were sustained through 24 months and generally greater with the higher vs lower tofacitinib dose. [Int J Rheum Dis 2019;doi:10.1111/1756-185X.13516]
The corresponding 3-month rates with 10 mg/5 mg tofacitinib/placebo were as follows: 69.2 percent/77.9 percent/27.5 percent for American College of Rheumatology (ACR)20 response; 36.9 percent/44.4 percent/9.5 percent for ACR50 response; 15.1 percent/22.4 percent/2.7 percent for ACR70 response; 8.5 percent/18.5 percent/2.6 percent for Disease Activity Score-28 with erythrocyte sedimentation (DAS28‐ESR); and 6.1 percent/12.3 percent/0.5 percent for Clinical Disease Activity Index (CDAI). HAQ‐DI improved by −0.5/–0.6/−0.1, respectively.
In terms of safety, serious adverse events (SAEs) for all tofacitinib doses in the Asia‐Pacific subpopulation occurred with the same frequency as that in the global population (incidence rate [IR], 9.4 per 100 patient-years for both), but more Asians discontinued treatment due to AEs (IR, 9.1 vs 7.2 per 100 patient-years). Reports of serious infections were especially more frequent in the Asia Pacific (IR, 3.7 vs 2.6 per 100 patient-years), with herpes zoster, pneumonia and tuberculosis being the most common.
The investigators partly attributed the difference in the incidence of serious infections to the higher proportion of Asia‐Pacific patients receiving concomitant corticosteroids vs the global tofacitinib population (72.1 percent vs 66.7 percent), with evidence pointing to corticosteroids as an independent risk factor for serious infections and herpes zoster in tofacitinib‐treated patients. [Rheumatology 2010;49:82‐90; Ann Rheum Dis 2017;76:1253‐1262; Arthritis Rheumatol 2017;69:1960‐1968]
“There are also differences in infection management between regions, and physicians in Asia may treat infections more aggressively and be more likely to recommend parenteral treatment or hospitalization vs other regions, resulting in these infections being considered serious,” they said.
Finally, it is possible that the difference in incidence of serious infection events may underlie the observed difference in the incidence of discontinuations due to AEs, as about 40 percent of AEs leading to discontinuation were infections, the investigators added.
The Asia-Pacific population comprised patients from Japan, Korea, China, India, Thailand, the Philippines, Malaysia and Taiwan. The mean age of patients across the tofacitinib-dose groups was 50.5 years, 86.9 percent were female, and mean disease duration was 7.1 years.
One important limitation of the analysis was that the LTE study population included patients who had successfully completed qualifying phase I–III studies, “a population in which tofacitinib was efficacious and well tolerated and may not reflect the wider population with RA in clinical practice,” according to the investigators.
“Furthermore, this subanalysis was not designed for direct comparison of results between the Asia‐Pacific and global study populations … therefore, any comparisons should be treated with caution,” they pointed out.