Divergence Between Physician- and Patient-Reported Measures of Tofacitinib Treatment Response in RA

Assessment of physician- and patient-reported measures among patients with rheumatoid arthritis (RA) who received tofacitinib highlighted key treatment considerations when using the American College of Rheumatology (ACR) 20/50/70 thresholds, according to a post-hoc analysis published in The Journal of Rheumatology.

Physicians are recommended to adjust treatment plans to prespecified goals, including remission and low disease activity (LDA), for patients with RA. Treatment options may include tofacitinib, adalimumab, and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), such as methotrexate (MTX). However, there is no standard composite measure used across clinical practices to evaluate disease improvement.

Study authors conducted a post-hoc analysis of phase 3 and phase 3b/4 trials to understand the effect of tofacitinib on ACR 20/50/70 response rates among patients with RA.

The studies included in the analysis were divided into 2 cohorts. The placebo-controlled cohort included pooled data from 3 phase 3 randomized controlled trials (RCTs; ORAL Scan [ClinicalTrials.gov Identifier: NCT00847613], ORAL Standard [ClinicalTrials.gov Identifier: NCT00853385], and ORAL Sync [ClinicalTrials.gov Identifier: NCT00856544]) of tofacitinib treatment among patients with active RA. The head-to-head cohort included data from a phase 3b/4 RCT (ORAL Strategy [ClinicalTrials.gov Identifier: NCT02187055]) of tofacitinib vs adalimumab.

Study authors assessed the ACR components that were most and least likely to be improved by treatment, met the improvement thresholds (≥20/50/70%) required for inclusion in the ACR response calculation, and evaluated at least 3 of the 5 secondary criteria: Clinician Global Assessment (CGA), Patient Global Assessment of Disease Activity (PtGA), patient-reported pain (Pain), Health Assessment Questionnaire-Disability Index (HAQ-DI), and C-reactive protein (CRP). Other composite measure included the Simplified Disease Activity Index (SDAI), and the Clinical Disease Activity Index (CDAI).

In the placebo-controlled cohort, ACR20/50/70 response and improvement rates at month 3 (end of placebo-controlled period) were similar to tofacitinib, combination csDMARDs and adalimumab, and csDMARD therapy alone, but were higher with active therapy vs placebo. The rates in ACR components were higher beginning at week 2 and month 1 with tofacitinib and adalimumab, respectively, vs placebo. In both cohorts, the mean percent improvements from baseline in the ACR components typically exceeded 20/50/70% at month 3 for all treatments.

In both cohorts, physician-reported measures typically contributed more to

ACR20/50/70 response rates, SDAI score, and CDAI score than patient-reported measures at month 3. However, these results showed that 23.5% to 45.0% of ACR70 responders receiving active treatment across both cohorts achieved SDAI or CDAI remission. In both cohorts, HAQ-DI typically contributed least to the achievement of ACR20/50/70 response rates.

The study limitations included use of a post-hoc analysis, lack of formal statistical testing, small sample size, and short-term analysis of 6 months. Limitations were also noted within the included studies, citing limited comparison between active treatments, pooled tofacitinib data, and nonresponder patient data.

The authors of the analysis concluded, “Taken together, these findings may help clinicians to interpret clinical study results, and to define expected responses to advanced therapies, to assist in setting treatment goals for patients during routine practice.”

Disclosure: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.

Reference

Bessette L, Mysler E, Kinch CD, et al. Impact of tofacitinib on components of the acr response criteria: post hoc analysis of phase III and phase IIIb/IV trials. J Rheumatol. Published on April 15, 2022. doi:10.3899/jrheum.210707