Long-Term Safety and Efficacy of Apremilast for Psoriatic Arthritis

Close-up of severe psoriatic arthritis of the feet, showing bent and inflamed toes on the right foot of a 44 year old woman. This form of arthritis is often associated with psoriasis, a chronic skin disorder characterized by a buildup of excess skin cells. Psoriatic arthritis causes pain, stiffness,and inflammation of the joints.
Researchers evaluated the efficacy and safety of apremilast in patients with psoriatic arthritis.

Apremilast was found to be effective and safe through 5-year follow-up for patients with psoriatic arthritis (PsA), according to study results published in Arthritis Research and Therapy.

Researchers evaluated the long-term extension phase of the Psoriatic Arthritis Long-term Assessment of Clinical Efficacy (PALACE) 1, 2, and 3 for clinical benefits and safety profile of apremilast, an oral phosphodiesterase 4 inhibitor, for patients with PsA. The PALACE 1, 2, and 3 studies were phase 3, randomized, double-blind, placebo-controlled trials evaluating apremilast at either 30 mg twice daily or 20 mg twice daily against a placebo for either 16 or 24 weeks, followed by the placebo cohort re-randomly assigned into either apremilast 30 mg twice daily or 20 mg twice daily until week 52.

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After trial completion, patients who joined this open-label long-term extension phase were evaluated after apremilast exposure for up to 260 weeks. Data — including improvement rates, changes in the swollen joint count and tender joint count, physical function, skin involvement, and adverse events (AEs) — were collected from patients with active PsA who met the Classification Criteria for Psoriatic Arthritis.

Of the 1493 patients included in one of the 3 PALACE studies, 63.2% (n = 331) of the apremilast 30-mg cohort and 58.7% (n = 304) of the apremilast 20-mg cohort completed 260 weeks of follow-up. At week 260 in the apremilast 30-mg cohort, 67.2% of patients reached a 20% improvement in American College of Rheumatology (ACR) response criteria, 44.4% of patients reached a 50% improvement in ACR response criteria, and 27.4% of patients reached a 70% improvement in ACR response criteria.

In addition, 82.3% of patients had improvements in the mean swollen joint count, and 72.7% of patients had improvements in the mean tender joint count.

Mean changes in the Maastricht Ankylosing Spondylitis Enthesitis Score and dactylitis at week 260 were −2.9 and −2.8, and improvements observed in the apremilast 30-mg cohort over the first 52 weeks were continued throughout week 260. Physical function, measured by the mean change in the Health Assessment Questionnaire-Disability Index, and skin involvement, measured by the Psoriasis Area and Severity Index, were maintained through week 260 for the apremilast 30-mg cohort. Apremilast 20 mg twice daily also demonstrated improvements in PsA signs and symptoms. No increases or worsening of AE rates were reported between weeks 52 and 260, with diarrhea, nausea, and headaches the most common AEs leading to discontinuation.

Limitations of this study include lack of analysis regarding the effect apremilast has on disease progression, restricted eligibility criteria, and potential biases of the open-label nature of the extension phase of the study.

The researchers concluded that “apremilast continued to demonstrate a favorable safety profile, with no new safety concerns identified, and was generally well tolerated for up to 5 years. Patients who continued therapy demonstrated sustained, clinically meaningful improvements in the signs and symptoms across various domains of PsA as well as in physical function.”

Celgene Corporation sponsored this study, and several authors reported associations with pharmaceutical companies. Please see the original reference for a full list of authors’ disclosures.


Kavanaugh A, Gladman DD, Edwards CJ, et al. Long-term experience with apremilast in patients with psoriatic arthritis: 5-year results from a PALACE 1-3 pooled analysis. Arthritis Res Ther. 2019;21(1):118.