Background/Purpose: Inhibition of phosphodiesterase (PDE) family enzymes is now recognized as target to develop new psoriatic arthritis (PsA) drugs. We conducted a systematic review to evaluate the benefits and harms of the first PDE4 inhibitors approved by the FDA (i.e., apremilast) for the treatment of PsA.

Methods: We searched electronic databases (i.e., The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and Web of Science) from inception to October 2014 with no restrictions. We also searched of ClinicalTrials.gov and the list of references of relevant citations to identify any additional citations not otherwise found. We included any controlled trials comparing treatment with apremilast alone or in combination with any DMARD versus placebo or other synthetic or biologic DMARD. Our primary outcome was the ACR modified response criteria for 50% improvement. Secondary outcomes included function measured by the health assessment questionnaire (HAQ), quality of life measured by the SF-36, disease activity, withdrawals, and serious adverse events. We calculated relative risks (RR) and their 95% confidence intervals (95%IC).

Results: Out of 246 citations, 5 double-blind, randomized controlled trials (RCTs) were included. All studies were funded by the manufacturer of the drug. The studies included a total of 2,005 patients (1,336 assigned to apremilast plus standard of care, and 669 to placebo plus standard of care). Mean age of participants ranged from 48.8 to 51.4 years; mean disease duration ranged from 6. 8 to 16.5 years; and between 45.5% to 52.6% were male. All studies were judged to have high risk of performance and detection bias since apremilast was compared to placebo until week 16, and then placebo non-responders received apremilast. At 16 weeks, ACR50 response rates were statistically significantly improved with apremilast 20 and 30 mg compared with control (RR 2.3, 95%CI 1.6-3.2 and 2.2, 1.6-3.2, respectively. HAQ scores were statistically significantly better with apremilast 20 and 30 mg than with control (MD -0.11, 95% CI -0.16, -0.06 and -0.16, 95% CI -0.21, -0.11, respectively). Quality of life scores were similar between apremilast 20 mg and control, but were significantly better in the apremilast 30 mg versus placebo (MD 2.6, 95%CI 1.7-3.4).  There was a statistically significant reduction from baseline in the DAS28 in favour of apremilast 20 and 30 mg (MD -0.42, 95%CI -0.53, -0.31 and -0.48, 95%CI -0.59, -0.37, respectively). No differences were observed in the withdrawals rates or serious adverse events between groups. These differences were sustained even after 24 weeks (Table).

Conclusion: Our findings suggest that apremilast (either 20 or 30 mg) in combination with standard of care is significantly more efficacious than standard of care alone for improving the symptoms of PsA. Further studies are needed to evaluate its effects in preventing disease progression (structural damage).

« Back to 2015 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-phosphodiesterase-4-inhibitor-for-psoriatic-arthritis-systematic-review-and-meta-analysis/