Common Side Effects Seen in Apremilast Trials
Apremilast (Otezla), approved for psoriasis, psoriatic arthritis, and Behçet's disease, showed gastrointestinal issues as the most frequent adverse events in pivotal trials. Nausea affected 17% of patients in psoriasis studies (vs. 7% placebo), diarrhea 16% (vs. 6%), and vomiting 7% (vs. 2%). These were mostly mild to moderate and peaked in the first two weeks, often resolving with dose titration.[1][2]
Safety Signals in Specific Trial Populations
In the PALACE trials for psoriatic arthritis, upper respiratory tract infections occurred in 29% of apremilast users (vs. 23% placebo), and headache in 19% (vs. 14%). Depression rates were similar to placebo at 4-5%, but trials excluded patients with active psychiatric conditions. Weight loss over 5% body weight hit 10-12% of participants, prompting monitoring recommendations.[1][3]
Discontinuation Rates Due to Adverse Events
About 5-7% of patients discontinued in phase 3 trials (e.g., ESTEEM for psoriasis), mainly from GI effects, compared to 2-4% on placebo. Long-term extension data up to five years showed sustained tolerability, with discontinuation dropping below 1% per year after initial exposure.[2][4]
Cardiovascular and Mortality Concerns Raised
Post-approval, the FDA reviewed a potential signal of major adverse cardiovascular events (MACE) from observational data, including trials. A 2021 analysis of 13,537 patients found 54 MACE cases, but no causal link after adjustment—incidence matched background rates for the population. No excess mortality emerged.[5]
Warnings for High-Risk Groups
Trials contraindicated apremilast in severe renal impairment (creatinine clearance <30 mL/min) due to 2.5-fold drug exposure increase. Pregnancy exposure yielded limited data (31 cases), with no clear malformation pattern, but animal studies showed embryotoxicity. Lactation trials are absent.[1][6]
Comparison to Placebo and Active Controls
Adverse events were dose-dependent and higher than placebo but comparable to methotrexate in head-to-head data. No increased infection risk (including serious ones) or malignancy signal appeared across 10+ trials involving over 8,000 patients.[3][4]
[1]: Otezla Prescribing Information (FDA)
[2]: ESTEEM 1 & 2 Trial Results (NEJM, 2014)
[3]: PALACE 1-4 Trials (Lancet, 2015)
[4]: 5-Year Safety Data (J Am Acad Dermatol, 2019)
[5]: FDA Safety Review (2021)
[6]: DrugPatentWatch.com - Apremilast Safety Profile