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Real‐world drug survival and reasons for treatment discontinuation of biologics and apremilast in patients with psoriasis in an academic center

Dear Editor, The use of systemic agents is considered standard of care in patients with moderate to severe psoriasis, and these therapeutic agents are marked by a favorable risk-benefit profile, however, are plagued by high attrition. One questionnaire-based survey of 692 patients who had previously taken a biologic agent found that patients discontinued their medications after 11 to 20.5 months. Our study aims to present additional real-world clinical data regarding the reasons behind discontinuation of these novel agents and the drug survival in an academic setting. A study cohort of 127 patients seen in a 5-year time frame at the departments of dermatology and/or rheumatology between June 2012 and April 2017 was identified by the following inclusion criteria: age greater than or equal to 18-years-old, visit diagnoses related to psoriasis and/or active psoriatic arthritis identified by ICD-9 and ICD10 codes, and use of etanercept, adalimumab, infliximab, secukinumab, ustekinumab, or apremilast. Patients were excluded if they were taking more than one systemic agent. The primary outcome measure was time to all-cause medication time to discontinuation (TTD) for any reason. Patients were censored if they did not discontinue the treatment at the end of study period, discontinued due to death, or if lost to follow-up. Survival curves were constructed using Kaplan-Meier analysis. Discontinuation was defined as termination of therapy for any reason, subdivided into primary failure (failure to achieve 75% reduction in PASI by week 12-16 of therapy) and secondary failure (loss of effect after time). Drug survival of biologic agents was defined as the time from initiation to discontinuation. The median survival time for all-cause treatment discontinuation was 444 days (95% CI: 361, 525) (Table 1). Secukinumab had the highest survival at 504 days (95% CI [240, undecided]), and adalimumab the lowest at 342 days (95% CI [280, 859]). There was no significant difference in TTD among the novel medications (Figure 1). There was no relationship between medical history and discontinuation (Table 2). Secondary failure was the most frequently reported reason for treatment discontinuation (Table 3). The next most common reason included “other” reasons such as concern for (latent) infection, underlying cancer, and so forth. This is followed by initial lack of efficacy, adverse events, then insurance problems. Patients who experienced initial lack of efficacy had shorter TTD than those in other groups (P < .05). On an individual drug basis, the most common reasons for discontinuation were initial lack of efficacy for apremilast; loss of efficacy for etanercept, adalimumab, ustekinumab, and secukinumab; and adverse events for infliximab (Table 4). Failure of biologic agents is usually due to loss of efficacy. The exception appears to be infliximab, which usually fails due to adverse events. In our study, most drugs similarly tended to fail due to secondary failure. Only infliximab failed most commonly due to adverse events. Some studies have reported significant differences in survival data between these drugs, particularly in favor of ustekinumab. In our study, secukinumab was the agent with the highest median TTD, though not significantly. Other studies report no significant difference in drug survival, coinciding with our study. Others have suggested that female gender, obesity, smoking, and metabolic syndrome are risk factors for treatment failure. None of these were seen in our study. The mechanism behind initial unresponsiveness and loss of response over time is not completely understood, but may be due to the development of autoantibodies or anti-drug antibodies. Limitations include a retrospective study design, small sample size, and variability in sample size for each medication, especially secukinumab. In conclusion, our data suggest that survival of these drugs is comparable, and the choice of agent should be individualized.