Risk of Serious Infection in Patients Receiving Systemic Medications for the Treatment of Psoriasis

Abstract

IMPORTANCE There is a need for better understanding of the comparative safety of systemic medications used in the treatment of psoriasis. OBJECTIVE To compare the risk of serious infection associated with biologic and nonbiologic systemic medications in patients with psoriasis. DESIGN, SETTING, AND PARTICIPANTS An observational cohort study was conducted using medical and outpatient pharmacy claims from 2 large US health insurance claims databases from January 1, 2003, through September 30, 2015. We included patients with a diagnosis of psoriasis who were new users of systemic medications for psoriasis. EXPOSURES Prescription claims for acitretin, adalimumab, apremilast, etanercept, infliximab, methotrexate, or ustekinumab. MAIN OUTCOMES AND MEASURES The primary outcome was serious infection, defined by inpatient discharge diagnosis International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Cox proportional hazards regression was used to compare rates of serious infection for each exposure (acitretin, adalimumab, apremilast, etanercept, infliximab, and ustekinumab) with the referent group (methotrexate). We used pairwise 1:1 propensity score (PS) matching to adjust for potential confounders, which were assessed during a 180-day baseline period prior to study drug initiation. Results from the 2 databases were pooled via fixed-effects analysis. RESULTS The databases included 31 595 patients in the Optum Clinformatics Data Mart and 76 112 patients in Truven MarketScan who were new users of acitretin, adalimumab, apremilast, etanercept, infliximab, methotrexate, and ustekinumab. Users of acitretin, apremilast, infliximab, and methotrexate were older and had higher baseline comorbidity scores than subcutaneous biologic users (adalimumab, etanercept, and ustekinumab). The pooled PS-matched analysis yielded a decreased rate of overall serious infection in users of apremilast (hazard ratio [HR], 0.50; 95% CI, 0.26-0.94), etanercept (HR, 0.75; 95% CI, 0.61-0.93), and ustekinumab (HR, 0.65; 95% CI, 0.47-0.89) compared with methotrexate. We did not find a different rate of overall serious infection among users of acitretin, adalimumab, and infliximab compared with methotrexate. Subanalysis by type of serious infection showed a significantly increased risk of cellulitis among users of acitretin compared with methotrexate (PS-adjusted HR, 1.76; 95% CI, 1.11-2.80). CONCLUSIONS AND RELEVANCE Among patients with psoriasis treated with systemic medications in 2 large US claims databases, new users of apremilast, etanercept, and ustekinumab had a decreased rate of serious infection compared with methotrexate.

Predicting, Preventing, and Managing Treatment-Related Complications in Patients With Inflammatory Bowel Diseases

“…There is no signal of excess infections related to the use of ustekinumab trials in IBD, and no excess risk of infection was reported in psoriasis. 19 Exposure to Janus kinase (JAK) inhibitors is associated with an increased risk of various infections, mainly herpes zoster. Based on data from randomized clinical trials of tofacitinib in ulcerative colitis, 20 the absolute risk of herpes zoster in patients aged older than 65 years is 95.5 events per 1000 person-years.…”

Considerations for safety in the use of systemic medications for psoriasis and atopic dermatitis during theCOVID‐19 pandemic

“…It does not suppress the immune system to the extent of the other conventional treatments for psoriasis. In an observational cohort study, there was no increased rate of overall serious infections among acitretin‐treated psoriasis patients vs methotrexate; acitretin increased risk of cellulitis compared to methotrexate (propensity score‐adjusted hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.11‐2.80), possibly due to skin fragility and Staphylococcus aureus colonization 15 . Therefore, acitretin has not shown increased viral/respiratory infection risk and can be safely used during the pandemic.…”

“…No cases of tuberculosis reactivation were reported 54 . In one observational cohort study of 107 707 systemically treated psoriasis patients, ustekinumab (HR: 0.65; 95% CI, 0.47‐0.89), apremilast (HR: 0.50; 95% CI, 0.26‐0.94) and etanercept (HR: 0.75; 95% CI, 0.61‐0.93) had decreased risks of overall serious infections compared with methotrexate 15 . Similar risks of infection between ustekinumab and placebo were reported by Lebwohl et al 59 Thus, treatment with ustekinumab may be considered relatively safe during the COVID‐19 pandemic; however, switching to specific IL‐23 inhibitors may be prudent.…”

Comparative risk of serious infections among real-world users of biologics for psoriasis or psoriatic arthritis

“…It is important to understand whether these findings from RCTs persist in real-world practice, where patients are more heterogeneous and drug utilisation is far less controlled 7. Evidence from observational studies between biologic and non-biologic drugs have yielded inconsistent findings: some have shown an increased risk,8 9 while others have not found a difference 10–14. To our knowledge, no published studies have yet quantified the comparative real-world risk of serious infections among IL-17, IL-12/23 and TNF inhibitors.…”