Critical Appraisal of the Tofacitinib Trial in Ankylosing Spondylitis

To the Editor,

We appreciate the randomised, double-blind trial of tofacitinib in ankylosing spondylitis by Harish and colleagues and thank the authors for their work in a resource-limited setting. Still, some methodological and reporting issues limit the interpretation of the results and should be clarified. ¹

First, although the authors acknowledge the small sample size, the trial included only 48 patients instead of the planned 100. The manuscript does not explain how this affects statistical power, nor does it provide analyses such as fragility or sensitivity checks to demonstrate the reliability of the P values in the event of small changes in the data. Small trials such as this one reduce generalisability and increase the risk of missing real effects or overestimating treatment benefits. Clear reporting of power calculations and checks for robustness would help address these concerns. ²

Second and especially for readers and meta-analysts, the study reports effect estimates between groups but does not indicate the precise nature of these results. Outcomes such as Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score–C-reactive protein (ASDAS-CRP), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), erythrocyte sedimentation rate (ESR)/CRP and serum cytokines are reported as point estimates or P values; however, the tables do not include 95% confidence intervals or consistent standard deviation or error values. Without these, it is hard to judge the importance or reliability of the results or to use them in meta-analyses. This also does not follow Consolidated Standards of Reporting Trials (CONSORT) guidelines, which recommend including measures of precision with effect estimates. ²

Third, the safety reporting lacks detail. With only 25 patients exposed to tofacitinib over 12 weeks at a single centre, there is not enough person-time to properly assess important JAK-inhibitor risks such as major cardiovascular events, cancer, blood clots, serious infections or death. Larger safety trials and regulatory reviews have found increased risks of these events with tofacitinib in higher-risk rheumatoid arthritis (RA) patients, so small studies such as this cannot rule out such harms. The manuscript should at least report the number of adverse events with person-time denominators and exact confidence intervals and clearly state that the current sample size is too small to detect rare but serious events. ³

In summary, the trial’s clinical findings are potentially important and worth sharing. However, clearer reporting of uncertainty, such as confidence intervals and standard deviations, checks for robustness and more transparent reporting of harms are needed. This will help readers, guideline panels and meta-analysts better understand and use these results.