Pain Management From Tofacitinib Mediated by Itch, Enthesitis in Psoriatic Arthritis

Study results suggest that inflammation may be a mediator of the overall effect of tofacitinib on pain relief in patients with psoriatic arthritis.

Among patients with psoriatic arthritis (PsA), the effect of tofacitinib on pain was mediated by itch, enthesitis, and C-reactive protein (CRP), according to the results of an analysis published in Rheumatology and Therapy.

This mediation analysis evaluated data from 2 randomized, placebo-controlled, double-blind, phase 3 trials: OPAL Broaden (ClinicalTrials.gov Identifier: NCT01877668) and OPAL Beyond (ClinicalTrials.gov Identifier: NCT01882439). Patients (N=329) with PsA who were randomly assigned to receive tofacitinib 5 mg twice a day or placebo were evaluated in this study for mediators of the pain relief associated with tofacitinib.

In the initiation model, the direct pain relief effect of tofacitinib on pain was 16.0% (P =.5274).

Tofacitinib mediated pain indirectly through the Itch Severity Item (ISI), Psoriasis Area and Severity Index (PASI), CRP level, swollen joint count (SJC), and Leeds Enthesitis Index (LEI) with an overall effect of 84.0% (P =.0009).

These results suggest that inflammation may be a significant mediator of the overall effect of tofacitinib on pain relief in patients with PsA.

Stratified by individual predictors, only ISI was significant on its own with a 64.4% effect (P =.0035). The other predictors included PASI with a -14.4% effect (P =.0979), LEI with a 9.5% effect (P =.2220), and SJC with a less than 0.1% effect (P =.9929).

A respecified model including ISI, CRP, and LEI indicated a 29.5% direct effect on pain from tofacitinib (P =.0579) with a 70.5% indirect effect (P <.0001). Similar to the initiation model, the largest indirect effect was observed for ISI (37.4%; P =.0002), followed by LEI (17.8%; P =.0157) and CRP (15.3%; P =.0107).

This study may have been limited as the OPAL Broaden and OPAL Beyond clinical trials used validated instruments to define inflammation. Using biological inflammation biomarkers as input may yield differing results.

Study authors concluded, “These results suggest that inflammation may be a significant mediator of the overall effect of tofacitinib on pain relief in patients with PsA. The majority of the effect of tofacitinib on pain was collectively mediated by itch, CRP, and enthesitis, with itch being the primary mediator of treatment effect.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

References:

de Vlam K, Mease PJ, Bushmakin AG, et al. Identifying and quantifying the role of inflammation in pain reduction for patients with psoriatic arthritis treated with tofacitinib: a mediation analysis. Rheumatol Ther. 2022;9(5):1451-1464. doi:10.1007/s40744-022-00482-5