In patients with psoriatic arthritis (PsA), tumor necrosis factor alpha (TNF-α), anti-interleukin (IL)-12/23, and anti-IL-17 agents demonstrated comparable efficacies in terms of enthesitis and dactylitis resolution,, according to a study published in The Journal of Rheumatology.
Dactylitis and enthesitis can impair joint function and negatively affect quality of life, and inflammatory mediators including TNF-α and various IL cytokines have been implicated in their pathogenesis. But evidence is lacking on the efficacy of anti-TNF-α and anti-IL biologics for extra-articular manifestations of PsA. Investigators sought to evaluate these agents for such purposes using a systematic literature review and meta-analysis in a first-of-its-kind analysis.
A systematic review and pooled meta-analysis of randomized controlled trials (RCTs) was conducted through February 2018 by searching PubMed, EMBASE (Ovid), Web of Science, Scopus, and the Cochrane Library for studies involving anti-TNF-α (infliximab, adalimumab, golimumab), anti-IL-17 (secukinumab, ixekizumab), and anti-IL-12/23 (ustekinumab) therapies for PsA. The latter 2 categories were collapsed into a single novel biologics category for comparison.
The primary outcomes were resolution of enthesitis and dactylitis, whereas secondary outcomes included the rate of 20% improvement in American College of Rheumatology criteria (ACR20) and mean change in Health Assessment Questionnaire scores between baseline and follow-up. Risk ratios (RRs) were calculated using a random effects model, and bias risks were evaluated by the Cochrane Risk of Bias tool.
A total of 19 RCTs (n=7254 patients) and 18 RCTs (n=6981) were included in the qualitative and quantitative syntheses, respectively. Both anti-TNF-α and novel biologics were significantly better at resolving dactylitis and enthesitis compared with placebo and were comparable to each other, with secukinumab performing the best among novel agents. There was a low overall risk for selection, detection, attrition, and reporting biases.
At 24 weeks, the pooled RR vs placebo for dactylitis resolution was 2.57 (95% CI, 1.36-4.84) for anti-TNF-α agents and 1.88 (95% CI, 1.33-2.65) for novel medications, with all biologics having a pooled RR of 2.07 (95% CI, 1.54-2.80). For enthesitis resolution at 24 weeks, the pooled RR vs placebo was 1.93 (95% CI, 1.33-2.79) for anti-TNF-α therapies and 1.95 (95% CI, 1.60-2.38) for novel biologics, with a pooled RR of 1.95 (95% CI, 1.63-2.32) for all biologics.
The 24-week overall pooled RR for ACR20 responses of all biologics vs placebo was 2.25 (95% CI, 1.86-2.73). Anti-TNF-α medications demonstrated a pooled RR of 2.23 (95% CI, 1.60-3.11), and novel biologics had a pooled RR of 2.30 (95% CI, 1.94-2.72), in terms of ACR20 responses.
Regarding mean change in Health Assessment Questionnaire from baseline compared with placebo, at 24 weeks, the overall change for all biologics was −0.27 (95% CI, −0.31 to −0.23). For anti-TNF-α drugs, the mean change was −0.29 (95% CI, −0.39 to −0.19), and for novel biologics, the mean change was −0.26 (95% CI, −0.31 to −0.22).
Study strengths included the use of high-quality RCTs with low bias risk. Study limitations included an inability to analyze data beyond 24 weeks, heterogeneity secondary to placebo group differences among RCTs, and variable biologic dosing regimens among RCTs.
“In conclusion, the pooled analysis demonstrates that the drugs targeting both TNF-α and IL-17 and IL-12/23 effectively resolve dactylitis and enthesitis, with no significant difference between either class of biologic,” noted the authors. They recommended that future research involve comparisons between individual biologics, using a network meta-analysis.
Disclosure: Dr Robert Gniadecki has received speaker’s honorarium from Mallinckrodt, Janssen, AbbVie, Novartis, and Leo Pharma and is on the advisory board for Mallinckrodt, Janssen, Amgen, AbbVie, Eli Lily, Sanofi, Novartis, and Leo Pharma. He is also an investigator in clinical trials for Janssen, Celgene, AbbVie, and Leo Pharma.
Mourad A, Gniadecki R. Treatment of dactylitis and enthesitis in psoriatic arthritis with biologic agents: a systematic review and meta-analysis [published online March 1, 2019]. J Rheumatol. doi:10.3899/jrheum.180797