Efficacy of TNF Agents vs Biologics for PsA-Related Dactylitis and Enthesitis

Both anti-tumor necrosis factor (TNF)-α agents and novel biologic agents have similar efficacy in treating clinical symptoms of dactylitis and enthesitis, according to research published in The Journal of Rheumatology.

Researchers conducted a systematic literature review and meta-analysis of randomized controlled trials examining the efficacy of multiple biologic agents in the treatment of psoriatic arthritis. Specifically, investigators examined evidence pertaining to dactylitis and enthesitis, with disease resolution as the primary endpoint.

Secondary outcomes included 20% improvement in American College of Rheumatology criteria (ACR20) response rates and changes in health-related quality of life measured by the Health Assessment Questionnaire (HAQ).

The meta-analysis included 18 studies, including 6981 patients. All 18 studies had ≥24-week efficacy data on ≥1 endpoint; 8 studies examined dactylitis resolution, 7 examined enthesitis resolution, 10 examined ACR20 response rate, and 9 examined HAQ response.

Treatment groups were stratified into an anti-TNF-α group (including adalimumab, etanercept, infliximab, certolizumab, and golimumab) and a novel biologic group (including ustekinumab, secukinumab, brodalumab, and ixekizumab), which targeted T-helper (TH)17 pathway cytokines, including interleukin (IL)-23, IL-17A, IL-17F, and IL-17.

For dactylitis resolution, at week 24, pooled risk ratio (RR) in the TNF-α inhibitor group was 2.57 (95% CI, 1.36-4-84) and the pooled RR for novel biologics was 1.88 (95% CI, 1.33-2.65). For enthesitis resolution, RRs were 1.93 (95% CI, 1.33-2.79) and 1.95 (95% CI, 1.60-2.38) for TNF-α inhibitors and novel biologics, respectively. Pooled RR for ACR20 response at week 24 was 2.25 (95% CI, 1.86-2.73), with an RR for both TNF-α and novel biologics of 2.23 (95% CI, 1.6-3.11) and 2.3 (95% CI, 1.94-2.72), respectively.

At week 24, mean change in HAQ scores was −0.29 (95% CI, −0.39 to −0.19) and −0.26 (95% CI, −0.31 to −0.22) for TNF-α and novel biologics, respectively. Researchers conducted a supplementary meta-analysis to compare the highest performing biologics for each outcome.

No differences were noted between infliximab and secukinumab in dactylitis resolution (RR 4.1 [95% CI, 2.03-8.29] and RR 3.19 [95% CI, 2.16-4.72]). No differences between infliximab and secukinumab were noted in ACR20 response. Golimumab and secukinumab were considered best-in-class for enthesitis resolution (RR 2.06 [95% CI, 1.28-3.31] and pooled RR 2.28 [95% CI, 1.55-3.36], respectively).

Several study limitations were noted. First, RTC data were limited past 24 weeks, so meta-analysis was not possible. In addition, the differences in placebo groups among clinical trials contributed to an inherent source of heterogeneity. Finally, the studies did not examine the effect of dose-optimized biologics.

The researchers of the study concluded that the pooled analysis “demonstrated that the drugs targeting TNF-α and IL-17 and IL-12/23 effectively resolved dactylitis and enthesitis, with no significant difference between the 2 classes of biologic treatment.”

Dr Gniadecki received speaker honoraria from AbbVie Inc. and Janssen-Cilag and is on the advisory board for AbbVie, Inc.; Eli Lilly and Company; Janssen-Cilag; LEO Pharma A/S; Novartis Pharmaceuticals Corporation; and Sanofi.

Reference

Mourad A, Gniadecki R. Treatment of dactylitis and enthesitis in psoriatic arthritis with biologic agents: a systematic review and metaanalysis [published online March 1, 2019]. J Rheumatol. doi:10.3899/jrheum.180797