Long-Term Safety and Effectiveness of Adalimumab for Moderate to Severe Psoriasis: Results from 7-Year Interim Analysis of the ESPRIT Registry

Abstract

Introduction: ESPRIT (NCT00799877) is an ongoing 10-year international prospective observational registry evaluating the long-term safety and effectiveness of originator adalimumab in routine clinical practice for adult patients with chronic plaque psoriasis. Herein, we report the long-term safety, effectiveness, and patient-reported outcomes (PROs) following adalimumab treatment over the first 7 years of the ESPRIT registry.

Methods: All treatment-emergent (All-TE) adverse events (AE) since the initial (first ever) dose of adalimumab were assessed. Physician Global Assessment (PGA) and PROs (PROs for US patients only) were evaluated during registry participation.

Results: As of 30 November 2015, 6051 patients in the ESPRIT registry were analyzed, representing 23,660.1 patient-years (PY) of overall adalimumab exposure. The incidence rates for All-TE serious AEs, serious infections, and malignancies were 4.4, 1.0, and 1.0 events per 100 PY (E/100PY), respectively. The standardized mortality ratio for TE deaths in the registry was 0.27 (95% CI 0.18-0.38). During the registry's first 7 years, PGA "clear" or "minimal" was achieved by >50% of patients at each annual visit, and among US patients, the mean improvement from baseline in different PROs was maintained.

Conclusion: No new safety signals were identified during the first 7 years of the registry, and safety was consistent with the known safety profile of adalimumab. The number of TE deaths was below the expected rate. During the registry's first 7 years, most of the patients remained free of All-TE cardiovascular events, serious infections, and malignancy. As-observed effectiveness of adalimumab and improvements from baseline in PROs were maintained through 7 years of registry participation.

Funding: Abbvie.

Trial registration: ClinicalTrials.gov identifier, NCT00799877.

Keywords: Adalimumab; Cardiovascular events; Effectiveness; Long-term safety; Malignancy; Patient-reported outcomes; Psoriasis; Registry; Serious infections.

Figures

Fig. 1

Study design and patient population of the ESPRIT observational registry. aOf the 6066 patients enrolled, 4 had dosing information unavailable in the interim analysis of the database, and 11 patients from one site in the US were excluded from all analyses since the physician was unavailable to confirm the safety information and data in the database. bStart dates are shown for clinical trials. cREVEAL and CHAMPION were among the feeder trials for the OLE; the number of patients in these trials were counted separately from OLE’s 196 patients. *Patients were evaluated 3 and 6 months post enrollment and then every 6 months for up to 10 years. Patients were followed at intervals determined by routine clinical practice or as recommended by national guidelines. Safety data are captured during the entire study period. Patients who discontinued the registry drug were encouraged to remain in the registry

Fig. 2

Number of patients based on duration of adalimumab exposure (All-Rx and new-Rx patient population). Overall exposure to adalimumab (outside of and within the registry) was calculated as the time from the initial (first ever) adalimumab dose to 14 days after the last adalimumab dose in the registry, excluding the total number of days of treatment interruption in the registry. Registry exposure to adalimumab (within the registry) was calculated as the time from the first adalimumab dose in the registry to 14 days after the last adalimumab dose in the registry, excluding the total number of days of treatment interruption (defined as >70 days without any adalimumab dose) in the registry. ADA adalimumab; All-Rx all-treated patient population, New-Rx new prescription patient population

Fig. 3

Kaplan-Meier plots of time to discontinuation from the registry and from the registry drug (adalimumab) (All-Rx and New-Rx patient populations). aTime of observation (first day to last day of registry participation) was used for time to registry discontinuation; registry exposure to adalimumab was used for time to registry drug discontinuation. All-Rx all-treated patient population, New-Rx new prescription patient population

Fig. 4

Incidence rates of All-TE cardiovascular events (1) and serious infections and malignancies (2) by time of event occurrence (All-Rx patient population). aThe AEs collected from rollover patients during feeder studies most likely occurred in the first years of overall exposure to adalimumab. A closer AE documentation in feeder studies is expected compared with registry AE collection and retroactive collection of AEs for patients who initiated adalimumab therapy outside of an AbbVie clinical trial before the registry. bPatients with ≥7 years of overall exposure to adalimumab are a selected subgroup from the overall population who had the longest exposure to adalimumab and potentially had a longer duration of disease. All-TE AE all treatment-emergent adverse event, All-Rx all-treated patient population, MI myocardial infarction, CVA cerebrovascular accident, CHF congestive heart failure, SI serious infection, NMSC non-melanoma skin cancer, ADA adalimumab, AE adverse event

Fig. 5

Time to first all-TE AE of interest (All-Rx patient population). aOverall exposure to adalimumab (outside of and within the registry). All-TE AE all treatment-emergent adverse event, All-Rx all-treated patient population, MI myocardial infarction, CVA cerebrovascular accident, CHF congestive heart failure, SI serious infection, NMSC non-melanoma skin cancer

Fig. 6

Standardized mortality ratios (SMR)a, overall and by gender (All-Rx and new-Rx patient population). aSMR was calculated as the ratio of observed to expected treatment-emergent deaths using the 2006 country-specific World Health Organization (WHO) mortality rates. All-Rx all-treated patient population, New-Rx new prescription patient population, PY patient years, CI confidence intervals

Fig. 7

Proportion of patients (as observed) achieving PGA “clear” or “minimal” (All-Rx and new-Rx patient population). Patients were not necessarily receiving adalimumab at the time of PGA assessment. Only a few selected patients left at 84 months. PGA physician’s global assessment, All-Rx all-treated patient population, New-Rx new prescription patient population

Fig. 8

Change from baseline (as observed) in DLQI scoresa (All-Rx and new-Rx patient population, US patients only). aDecrease in DLQI scores denotes improvement. N* number of patients in as-observed population for respective visit; only a few selected patients left at 84 months. PGA physician’s global assessment, All-Rx all-treated patient population, New-Rx new prescription patient population

Fig. 9

Change from baseline (as observed) in WPAI scoresa (All-Rx and New-Rx patient population, US patients only). aDecrease in WPAI subscores denotes improvement. N* = number of patients in as-observed population for respective visit; only a few selected patients left at 84 months. WPAI work productivity and activity impairment, TWPI total work productivity impairment, TAI total activity impairment, presenteeism impairment while working, All-Rx all-treated patient population, New-Rx new prescription patient population