To the Editor:
We read with interest the recent article by Braña et al1 evaluating the persistence and safety of tofacitinib (TOF) under real-world conditions in a refractory population of patients with psoriatic arthritis (PsA), with a special focus on the enthesitis phenotype. Their findings provide valuable insight into the retention profile of TOF in a population largely underrepresented in randomized controlled trials. We would, however, like to comment on one methodological aspect that merits further discussion: the lack of adherence data in the analysis of treatment persistence.1
Though the authors define persistence as time from treatment initiation to discontinuation and analyze this outcome using robust survival techniques, they do not incorporate any formal measurement of adherence.1 This distinction is critical because persistence and adherence, though related, represent distinct constructs.2 Persistence refers to the length of time a patient continues treatment without an unacceptable gap or permanent discontinuation. In contrast, adherence relates to how closely the patient follows the prescribed regimen, including timing, dosing, and frequency of administration.3 Without adherence data (eg, pharmacy refill rates or patient-reported compliance), persistence estimates may overstate real-world drug performance.
Although the study presents valuable real-world data on the persistence of TOF in patients with PsA-related enthesitis, adherence was not assessed prior to the persistence analysis. This limitation is not explicitly discussed by the authors,1 but it is important to note, as the lack of adherence data may influence persistence outcomes. Without objective adherence measures, discontinuation may be attributed to treatment failure, when in fact it could reflect suboptimal medication-taking behavior. Acknowledging this limitation would strengthen the interpretation of the persistence findings reported. Moreover, this limitation was not explicitly acknowledged in the discussion section.1 Therefore, the reported persistence outcomes should be interpreted with caution, as they do not account for whether patients actually followed the prescribed treatment regimen during the observation period. This omission is relevant because nonadherence can confound the interpretation of persistence-related outcomes or overly optimistic estimates of treatment effectiveness and safety.4,5
The clinical implications of this distinction are highly relevant in PsA. The therapeutic efficacy and long-term benefit of biologic treatments depend not only on maintaining therapy over time but also on correct and consistent administration. This distinction is particularly important in chronic diseases such as PsA, where suboptimal adherence is associated with increased relapse risk, disease progression, and greater healthcare resource utilization.4
The inclusion of adherence assessment in persistence studies aligns with the evolving 6P Medicine framework (personalized, predictive, preventive, participatory, population-based, and persistent), which emphasizes the need to integrate behavioral dimensions of treatment into clinical and policy decision making.6 Recognizing the multidimensional nature of patient behavior, this model advocates for a comprehensive assessment that integrates persistence, adherence, and other behavioral factors into clinical and policy decision making. We suggest that future real-world studies in PsA should systematically incorporate validated adherence measures (eg, pharmacy refill data, electronic monitoring, patient-reported adherence scales) into persistence analyses. This would allow for a more comprehensive and clinically meaningful understanding of treatment dynamics and will better inform both clinical and policy decision making. Comprehensive evaluation of both persistence and adherence provides a more accurate picture of real-world treatment dynamics and can better inform therapeutic choices, patient education strategies, and healthcare planning.7-9
We commend the authors for their valuable contribution to the understanding of TOF use in PsA and particularly for highlighting the potential benefit in patients with enthesitis.1 Nevertheless, we encourage future studies to systematically include adherence measurements when evaluating persistence. Doing so will improve the quality of real-world data and help clinicians make more informed decisions regarding the long-term management of PsA.
Footnotes
CONTRIBUTIONS
JBB, AVR, and SCU performed the investigation, analyzed the data, provided resources, supervised the project, and wrote the original draft of the manuscript. JBB also reviewed and edited the manuscript. The authors have read and agreed to the published version of the manuscript.
FUNDING
No funding or sponsorship was received for this study or for the publication of this article.
COMPETING INTERESTS
The authors declare no conflicts of interest relevant to this article.
ETHICS AND PATIENT CONSENT
This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. Ethics approval and patient consent are not required according to the authors’ institutions.
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