Discussion
PsA, SpA, fatigue, PsA/Spondylarthritis, pain, enthesopathy, tofacitinib-treated, arthritis pain, enthesitis
ENTHESITIS, HAND ARTHRITIS, DISEASE, REMISSION, ENTHESOPATHY, REGRESSION, DISEASE, ENTHESITIS
In phase 3 studies of patients with PsA (OPAL Broaden and OPAL Beyond), greater improvements in enthesitis and more frequent enthesitis resolution were reported at month 3 with tofacitinib vs placebo [At month 3, improvements in LEI were greater with tofacitinib 10 mg BID vs placebo in patients with enthesitis at the lateral epicondyle humerus or medial femoral condyle at baseline (10 mg BID) and in patients with 3–6 affected sites (5 mg BID); while greater improvements in SPARCC were observed with tofacitinib vs placebo in patients with enthesitis in both upper and lower sites at baseline (10 mg BID at month 3) and in patients with > 2– ≤ 5 affected SPARCC sites at baseline (5 mg BID at month 1 and both doses at month 3). Improvements from baseline in enthesitis in tofacitinib-treated patients were observed as early as month 1 and maintained to month 6; greatest improvements were seen in patients with greatest severity at baseline. Regardless of baseline enthesitis location or severity, enthesitis presence generally decreased over time with tofacitinib treatment. At month 6, relapse of previously resolved enthesitis was observed in ≤ 40% of tofacitinib-treated patients with enthesitis at baseline. Disease activity remission rates and fatigue scores were generally similar across treatments. Tofacitinib treatment was associated with greater LDA rates or improvements from baseline in pain scores compared with placebo, though fluctuations were observed over time.Through month 6, presence of enthesitis, as assessed by LEI, was similar across baseline enthesitis location, indicating that no site was at a greater risk for enthesitis. Enthesitis by SPARCC was more common in patients with enthesitis in both upper and lower sites at baseline. These differences in treatment response are aligned with results from a previous analysis of the US CorEvitas (formerly Corrona) PsA/Spondylarthritis (SpA) Registry, where impact of enthesitis, assessed by SPARCC, on disease activity was highest in patients with enthesitis at both upper and lower sites, followed by lower sites only and upper sites only [Multivariable linear regression analyses demonstrated that enthesitis at the lateral epicondyle humerus and Achilles tendon insertion, as assessed by LEI, was significantly associated with change from baseline in arthritis pain scores at month 3 following treatment with tofacitinib 5 mg BID, suggesting that these sites may have a greater role on disease activity. When assessed by SPARCC, baseline enthesitis severity (specifically, > 5 vs 0 affected sites comparison) was significantly associated with change from baseline in FACIT-F total and arthritis pain scores in the pooled (months 3 and 6) and individual tofacitinib groups (tofacitinib 5 mg BID: month 6 for FACIT-F total and arthritis pain scores; tofacitinib 10 mg BID: month 3 for FACIT-F total scores, months 3 and 6 for arthritis pain scores); however, no significant association between baseline enthesitis location and change from baseline in FACIT-F total and arthritis pain scores was identified in the pooled or individual tofacitinib groups. This finding suggests that enthesitis severity, and not location, may have a greater impact on treatment response for patients; however, in the US CorEvitas PsA/SpA Registry analysis, enthesitis presence in lower or both upper and lower sites was significantly associated with greater pain and fatigue score [In this analysis, development of de novo enthesitis was low and similar for tofacitinib and placebo. Interestingly, when assessed by LEI, emerging enthesitis at the lateral epicondyle humerus was observed at all time points across treatments. It should be noted that enthesopathy at the lateral epicondyle humerus is not infrequent in the general population [The effects of other PsA treatments on individual enthesitis sites or differing enthesitis severities have been reported previously. Efficacy of ixekizumab on enthesitis resolution rates was generally consistent across locations when assessed by LEI [Limitations of this study include the post hoc nature of the analysis, low patient numbers in several enthesitis location or severity subgroups, and lack of adjustment for multiple comparisons. Additionally, comparisons with placebo were restricted to 3 months, and the effects of tofacitinib on enthesitis were only assessed up to month 6, consistent with the original study designs. The clinical enthesitis assessments used also have known limitations. While LEI was designed specifically to assess enthesitis in patients with PsA [