Apremilast Shows Low Persistence Among Patients with Psoriatic Arthritis

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Results from a large observational retrospective cohort of ≥500 patients with PsA show relatively low drug persistence of apremilast, an oral PDE4 inhibitor.

An observational, retrospective analysis of a large cohort of patients with psoriatic arthritis (PsA) found a relatively low persistence rate for apremilast, an oral phosphodiesterase-4 inhibitor, with 6-month and 1-year survival rates of 50.3% and 31.3%, respectively.1

According to the analysis, treatment discontinuations were mainly related to joint inefficacy, side effects, and inadequate improvement in skin symptoms – patient demographics, socioeconomic status, obesity, and the Charlson comorbidity index showed no significant influence on treatment discontinuation.

“Treatment discontinuation was mainly due to joint inefficacy, advocating for more studies for proper patient selection to assure treatment effectiveness and persistency,” wrote the investigative team, led by Amir Haddad, rheumatology unit, Carmel Medical Centre.

Drug therapy persistence represents treatment effectiveness and tolerability in the real world. Given the amount of available PsA treatment options, it can be crucial to describe treatment persistence based on clinical experience – clinicians can make more informed decisions about the best treatment option to promote symptom remission and functional recovery and reduce healthcare costs.

By inhibiting phosphodiesterase 4, apremilast reduces the production of multiple cytokines involved in the pathogenesis of psoriatic disease, including TNFα and, IL-23. In phase 3 clinical trials, apremilast has shown effectiveness and a satisfactory safety profile in patients with active PsA.2 However, although real-world data have been reported in patients with psoriasis, there are limited data in the psoriatic arthritis setting. Haddan and colleagues thus assessed the treatment persistence of apremilast among patients with PsA, aiming to identify characteristics associated with treatment discontinuation in a real-world setting.

All patients aged ≥18 years diagnosed with PsA were retrospectively identified from a large health database in Israel from January 2016 until June 2021. Patients were followed until medication stop data, death, or the end of the observation period. Non-persistence was considered if a 90-day (3 months) interval run out of the original apremilast prescription refilling was exceeded, to prevent misclassifying short absences as non-persistence.

Investigators extracted demographic data, Charlson comorbidity index, and concomitant and previous use of conventional and biologic DMARDs. Reasons for treatment discontinuation for apremilast were manually retrieved from the patient’s medical record in the database. For analysis, the time to discontinuation was estimated using Kaplan-Meier curves and compared among patient subgroups.

Overall, a total of 568 patients with PsA treated with apremilast were identified, with a mean age of 55.3 years, and consisting of 332 females (58.5%). Of the population, 38.4% were obese (BMI >30), 75.3% had a Charlson comorbidity index >1, 24.1% were on concomitant treatment with methotrexate, and 72.4% were biologic naive.

The mean persistent period was 6.1 months (95% CI, 5.2 – 6.9), wherein only 16.9% of patients remained persistent on apremilast. Concomitant treatment with methotrexate and prior history of biologic therapy showed no effect on drug persistency (log rank, P = .957 and log rank, P = .082, respectively).

Investigators identified no differences regarding age, sex, socioeconomic status, ethnicity, and obesity status between patients who were persistent compared to those who discontinued apremilast. The causes for treatment discontinuation were due to lack of skin efficacy in 19.4% of patients, lack of joint efficacy in 33.3%, combined skin and joint inefficacy at 2.3%, side effects in 23.9%, and other reasons in 12.4%.

Haddad and colleagues suggested the need to take the differences in study design, definition of drug persistency, and patient population into consideration when viewing the results in contrast to other studies of apremilast. However, they noted the study provided important real-world data in a large, diverse patient population with PsA, which may reinforce the results across diverse healthcare settings.

“More research is needed to clarify the role of apremilast in the treatment of PsA, find acceptable patient selection criteria to assure treatment success and persistence, improve treatment planning, and more efficiently spend societal economic resources,” investigators wrote.


  1. Haddad A, Stein N, Lavi I, Shynkar L, Bergman I, Feldhamer I, Cohen AD, Saliba W, Zisman D. Treatment Persistence of Apremilast Among Patients with Psoriatic Arthritis. Biologics. 2023;17:129-136
  2. Cutolo M, Myerson GE, Fleischmann R, et al. A Phase III, randomized, controlled trial of apremilast in patients with psoriatic arthritis: results of the PALACE 2 trial. J Rheumatol. 2016;43(9):1724–1734. doi:10.3899/jrheum.151376