Comparison of Real-World On-Label Treatment Persistence in Patients with Psoriatic Arthritis Receiving Guselkumab Versus Subcutaneous Tumor Necrosis Factor Inhibitors

Abstract

Background: Treatment persistence among patients with psoriatic arthritis (PsA) is essential for achieving optimal treatment outcomes. Guselkumab, a fully human interleukin-23p19-subunit inhibitor, was approved by the United States (US) Food and Drug Administration for the treatment of active PsA in July 2020, with a dosing regimen of 100 mg at week 0, week 4, then every 8 weeks. In the Phase 3 DISCOVER-1 and DISCOVER-2 studies of patients with active PsA, 94% of guselkumab-randomized patients completed treatment through 1 year and 90% did so through 2 years (DISCOVER-2). Real-world evidence is needed to compare treatment persistence while following US prescribing guidelines (i.e., on-label persistence) for guselkumab versus subcutaneous (SC) tumor necrosis factor inhibitors (TNFis).

Methods: Adults with PsA receiving guselkumab or their first SC TNFi (i.e., adalimumab, certolizumab pegol, etanercept, or golimumab) between 14 July 2020 and 31 March 2022 were identified in the IQVIA PharMetrics^® Plus database (first claim defined the treatment start date [index date]). Baseline characteristics and biologic use (biologic-naïve/biologic-experienced) were assessed during the 12-month period preceding the index date. Baseline characteristics were balanced between cohorts using propensity-score weighting based on the standardized mortality ratio approach. The follow-up period spanned from the index date until the earlier of the end of continuous insurance eligibility or end of data availability. On-label persistence, defined as the absence of treatment discontinuation (based on a gap of 112 days for guselkumab or 56 days for SC TNFi) or any dose escalation/reduction during follow-up, was assessed in the weighted treatment cohorts using Kaplan-Meier (KM) curves. A Cox proportional hazards model, further adjusted for baseline biologic use, was used to compare on-label persistence between the weighted cohorts.

Results: The guselkumab cohort included 526 patients (mean age 49.8 years; 61.2% female) and the SC TNFi cohort included 1953 patients (mean age: 48.5 years; 60.2% female). After weighting, baseline characteristics were well balanced with a mean follow-up of 12.3-12.4 months across cohorts; 51.5% of patients in the guselkumab cohort and 16.7% in the SC TNFi cohort received biologics in the 12-month baseline period. Respective rates of treatment persistence at 3, 6, 9, and 12 months were 91.2%, 84.1%, 75.9%, and 71.5% for the guselkumab cohort versus 77.3%, 61.6%, 50.0%, and 43.7% for the SC TNFi cohort (all log-rank p < 0.001). At 12 months, patients in the guselkumab cohort were 3.0 times more likely than patients in the SC TNFi cohort to remain persistent on treatment (p < 0.001). Median time to discontinuation was not reached for the guselkumab cohort and was 8.9 months for the SC TNFi cohort.

Conclusion: This real-world study employing US commercial health-plan claims data to assess on-label treatment persistence in PsA demonstrated that, at 12 months, guselkumab was associated with a 3 times greater likelihood of persistence compared with SC TNFi.

Fig. 1

Study design schema. ^a,bICD-10 International Classification of Disease, 10th revision, PsA psoriatic arthritis, SC subcutaneous, TNFi tumor necrosis factor inhibitor, US United States. ^aA validated algorithm for identifying patients with PsA in US claims data was used [21]. ^bPatients could be biologic-naïve or biologic-experienced during the 12-month baseline period but were naïve to treatment with guselkumab or TNFi agents. ^cThe SC TNFi cohort included patients receiving a first SC TNFi. ^dDiagnoses for PsA include claims on the index date. Patients with PsA were identified based on ≥ 2 PsA diagnoses (ICD-10 code L40.5x) ≥ 30 days apart and ≥ 1 prescription claim for a PsA-related medication

Fig. 2

Identification of the study population of patients with PsA receiving guselkumab or an SC TNFi.^aICD-10 International Classification of Disease, 10th revision, IV intravenous, PsA psoriatic arthritis, SC subcutaneous, TNFi tumor necrosis factor inhibitor. ^aThe SC TNFi cohort is defined as patients with an index claim for an SC TNFi (i.e., adalimumab, certolizumab pegol, etanercept, or golimumab). ^bSpecific conditions for which the index agent may be initiated included ankylosing spondylitis, calcium pyrophosphate deposition disease, gout, non-radiographic axial spondyloarthritis, other spondyloarthropathies, post infectious and reactive arthropathies, relapsing polychondritis, rheumatoid arthritis, systemic connective tissue disorders, or unclassified connective tissue disease

Fig. 3

Kaplan-Meier analysis of on-label persistence in weighted guselkumab and SC TNFi cohorts: ^aprimary analysis (gap of twice the duration of time between administrations as per FDA label). bDMARDbiologic disease-modifying anti-rheumatic drug, CIconfidence interval, FDA Food and Drug Administration, SC subcutaneous, TNFi tumor necrosis factor inhibitor. ^a Propensity score weighting based on the standardized mortality ratio weighting approach was used to adjust for differences in baseline characteristics between the guselkumab and SC TNFi cohorts. Weights were estimated using a multivariable logistic regression model. Baseline covariates included all demographic and clinical characteristics reported in Table 1, with the exception of baseline use of bDMARDs, which was included in the adjusted Cox proportional hazard models. ^b Cox proportional hazard models were used to compare risk of discontinuation between the weighted guselkumab and SC TNFi cohorts. Models were adjusted for baseline use of bDMARDs. ^c Patients at risk of having the event are patients who have not had the event and have not been lost to follow-up at that point in time