PracticeUpdate Dermatology Best of 2018

EADV 2018 33

The Anti-TNF α Class Improves Dactylitis and Enthesitis of PsA Better Than Newer Biologics Efficacy of a biologic against dactylitis and enthesitis of psoriatic arthritis was shown for the first time. I n the first study to analyze and combine existing data in the literature to show the effectiveness of dactylitis and enthesitis resolution following biologic treatment, the anti-tumor necro- sis factor α biologic class was shown to confer greater effect than newer biologics. This outcome of a systematic literature search was reported at the EADV 2018. using a random effects model. Overall, 19 randomized, controlled trials were included in the review for a total of 13,758 patients assessed for the four outcomes. The overall pooled risk ratios at weeks 12–16 and 24 for dactyli- tis were 0.77 (95% CI 0.61–0.97), and 0.57 (95% CI 0.47–0.70), respectively. Pooled risk ratios at week 24 for anti-tumor necrosis factor α bio- logics were 0.28 (95% CI 0.19–0.41) vs:

Ahmed Mourad, MD, and Robert Gniadecki, MD, of the University of Alberta, Edmonton, Canada, conducted a literature review on dactylitis and enthesitis resolution, American College of Rheu- matology 20% (ACR 20) improvement, and Health Assessment Questionnaire (HAQ) scores following biologic treatment and to create a pooled risk ratio for each outcome. The PubMed, Cochrane Library, Embase, Web of Science, and Scopus electronic databases were used. The study included rand- omized controlled trials investigating biologic treatment outcomes for dactylitis, enthesitis, and ACR 20 and HAQ scores. Primary outcomes of interest were the resolution of dactylitis and enthesitis. Secondary outcome measures were the achievement of ACR 20 and mean change in HAQ score. Meta-analyses were conducted on these outcomes at weeks 12–16 and 24, and were incorporated as pooled risk ratios in forest plots proportions of patients who achieved 30% improvement from baseline score on the Severity of Alopecia Tool (PF-06651600: 48% [90% confidence interval 34%, 61%], P < .001; PF-06700841: 60% [90% confidence interval 46%, 72%], P < .001). Significantly greater proportions of patients achieved 50%, 75%, 90%, and 100% improvement from baseline score as well. In addition, significantly more patients experienced eyelash and eyebrow improvement with JAK inhibition vs placebo. Significant improvements vs placebo were observed in patients with alope- cia totalis and alopecia universalis. Both JAK inhibitors were found to be safe and well tolerated. The most common adverse effects were in the categories of infec- tion, gastrointestinal system, and skin/subcutaneous tissue. No cases of herpes zoster reactivation were observed. Dr. Sinclair explained that alopecia areata affects up to 147 million individuals globally. No reliably effective therapies are availa- ble. Such compounds are needed, especially for patients with chronic, extensive disease. Studies assessing JAK inhibitors have been encouraging. Dr. Sinclair concluded that these phase II trial data suggest that 24 weeks of treatment with either PF-06651600 or PF-06700841 were found to be efficacious, safe, and well tolerated in patients with moderate to severe alopecia areata, including patients with alopecia totalis and alopecia universalis. He said in a press release, “People living with alopecia areata face a difficult journey as there are currently no approved treat- ments. The results seen with these JAK inhibitors are very encouraging for me as a clinician as they signal a potential new way to think about the treatment of alopecia, which may bring hope for patients with this distressing condition.” www.practiceupdate.com/c/73892

• Ustekinumab, relative risk 0.76 (95% CI 0.67–0.86) • Ixekizumab, relative risk 0.54 (95% CI 0.34–0.59) • Secukinumab, relative risk 0.58 (95% CI 0.51–0.67)

A significantly lower likelihood of developing enthesitis at week 24 (risk ratio 0.72, 95% CI 0.64–0.82) vs weeks 12–16 (risk ratio 0.83, 95% CI 0.69–1.00) was observed. Pooled enthesitis risk ratio for anti-tumor necrosis factor α bio- logics at week 24 was 0.44 (95% confidence interval 0.29–0.66). Pooled risk ratios were:

• Ustekinumab, relative risk 0.82 (95% CI 0.76–0.89) • Ixekizumab, relative risk 0.79 (95% CI 0.66–0.94) • Secukinumab, relative risk 0.67 (95% CI 0.54–0.84)

The relative risk for achieving ACR 20 response at weeks 12–16 was 2.99 (95% CI 2.11–4.22). Relative risk at week 24 was 2.45 (95% CI 1.96–3.06). Improvement in HAQ score favored biologic treatment at weeks 12–16 (mean change –0.28, 95% CI –036 to –0.21) and 24 (mean change –0.24 (95% CI –0.28 to –0.21). Enthesitis and dactylitis often occur in the lower extremities and may cause tenderness or pain while standing and walking. They also may limit the ability to hold or grasp objects and affect fine motor function. They are associated with impaired function, may negatively impact quality of life, and are difficult to treat using con- ventional treatments. Both enthesitis and dactylitis contribute significantly to the per- ceived burden of disease among patients with psoriatic arthritis. Dactylitis is considered a marker of severity of psoriatic arthritis. Therapeutic options for psoriatic arthritis include systemic ther- apy with conventional disease-modifying antirheumatic drugs or biological agents, though little evidence supports conventional dis- ease-modifying antirheumatic drugs for either enthesitis or dactylitis. When assessing new therapies for psoriatic arthritis, it is important to understand the impact treatment exerts on hallmark features of the disease, such as enthesitis and dactylitis. Dr. Mourad concluded that in the first study to analyze and combine existing data in the literature to show the effectiveness of dactylitis and enthesitis resolution following biologic treatment, the anti-tu- mor necrosis factor α class was shown to confer greater effect than the newer biologics ustekinumab, ixekizumab, and secukinumab. Prolonged treatment adherence appears to be an important factor in resolving dactylitis and enthesitis because better rates of res- olution were observed at week 24 than during weeks 12–16. No significant differences in ACR 20 or HAQ scores were observed between the different classes of biologic drugs. www.practiceupdate.com/c/73858

VOL. 2 • NO. 4 • 2018