Long term safety findings confirmed in phase III trials of Otezla (apremilast) in plaque psoriasis and psoriatic arthritis- Celgene

Celgene has announced long-term safety findings from ongoing phase III clinical trials (the ESTEEM 1 and 2 and PALACE 1-3 trials) of Otezla (apremilast) which included patients with moderate to severe plaque psoriasis (ESTEEM) and active psoriatic arthritis (PALACE) who were treated with apremilast 30 mg twice-daily. Patients with psoriatic arthritis were treated with Otezla alone or in combination with concomitant disease-modifying anti-rheumatic drugs (DMARDs), including methotrexate. 2,242 patients were included in the pooled safety analysis up to 16 weeks (placebo n=913; APR30 n=1,329), with 1,905 patients (3,527.5 patient years) receiving apremilast in the APR-exposure period up to 156 weeks.

Across both trial programmes up to 16 weeks, the most common adverse events (AEs) (at least 5 percent of patients) among patients on apremilast were diarrhoea, nausea, headache, upper respiratory tract infection, and nasopharyngitis. Most cases of diarrhoea/nausea were mild to moderate in severity, occurred during the first 2 weeks of apremilast dosing and generally resolved in one month. Discontinuation rates of apremilast due to diarrhoea and nausea occurred at rates of 1.3 percent and 1.7 percent, respectively, during the 0 to 52 week apremilast exposure period and 0.0 percent for both AEs during the longer than 104 to 156 week apremilast exposure period. The exposure-adjusted incidence rates (EAIR/100 patient years) for AEs, serious AEs and discontinuations due to AEs did not increase with increasing cumulative exposure during the apremilast-exposure period (0 to 156 weeks; 3,527.5 patient-years); this was confirmed by assessment of rates on a year-by-year exposure basis.

The incidences (EAIR/100 patient years) of major adverse cardiovascular events (MACE), malignancies, and serious infections for patients on apremilast were comparable to placebo up to 16 weeks and remained low with prolonged exposure. No serious opportunistic infections or clinically meaningful effects on laboratory measurements were reported. Rates for depression or suicidality did not increase with increasing cumulative long-term apremilast exposure. Most patients taking apremilast maintained body weight within 5 percent of baseline; with 21.1 percent experienced more than 5 percent weight loss over the 156 week apremilast-exposure periods. The rate of treatment discontinuation due to weight loss was low.

In addition, a retrospective analysis of results from ESTEEM 1 and 2 trials examined the potential of an alternative tool to measure psoriasis disease severity. Improvement in Psoriasis Area and Severity Index (PASI) score remains the most commonly used severity assessment in clinical development and in practice, however its limitations � including scoring complexity and insensitivity to changes � mean that there may be opportunities to improve how psoriasis patients are assessed. Data were presented at the European Academy of Dermatology and Venereology (EADV) Annual Congress in Vienna, Austria.