Background/Purpose:  Apremilast is a small molecule,specific phospodiesterase4 inhibitor under investigation for a number of inflammatory conditions, including psoriasis and psoriatic arthritis. We report results of an interim safety analysis of a phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel-group study in 18 patients with erosive hand osteoarthritis (EHOA).

Methods: Subjects with a diagnosis of EHOA, fulfilling the classification criteria of the American College of Rheumatology with a disease duration of ≥6 months, were randomized to oral apremilast 20 mg BID or matching placebo. All subjects with at least the baseline visit reported were included in the analysis. Adverse events (AEs) were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0.

Results: A total of 76 AEs were reported since the study started in 2010 (FPFV 29-Nov-2010, data lock for interim analysis 30-May-2012). Most AEs were mild to moderate in severity (93.5%); only 5 (6.6%) were grade 3 (severe). No grade 4 or 5 AEs were reported. The most commonly reported AEs were related to “Pain ” 38% (Pain-Head/headache in 6/11 patients (55%) and Pain-Joint in 3/11 patients (27%) or “Gastrointestinal” (18%), with the most frequent AEs being headache (16%), fatigue (8%), diarrhea (7%), and joint pain (7%). Thirty-five AEs (46%) were considered possibly treatment related. Of these, 97% were mild to moderate and only 1 (3%) was grade 3 (hypotension). The most frequent treatment-related AEs were headache (9/35 [26%]), fatigue (3/35 [9%]), and diarrhea (3/35 [9%]). No serious AEs or deaths were reported during the study.

Conclusion: Given the lack of treatment options for patients with EHOA, there is an unmet need for an effective treatment to reduce the burden of this disease. Considering the pathophysiology of EHOA, mechanism of action of phosphodiesterase 4 inhibitors, and the reported AEs in earlier trials, we conclude that apremilast may also be well tolerated in patients with EHOA. Apremilast, if proven to be efficacious in ongoing investigations, will be an interesting treatment option for patients with EHOA.