SUMMARY

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• A Bayesian network meta-analysis (NMA) indirectly compared the relative treatment effect of TREMFYA to other targeted therapies for psoriatic arthritis (PsA), including interleukin-17A inhibitors (ie, ixekizumab and secukinumab), on joint and skin efficacy outcomes and safety in adults with active PsA.^1,2
• A real-world, retrospective study evaluated treatment persistence in adult patients with PsA who were newly initiated on subcutaneous (SC) TREMFYA vs SC IL-17A inhibitors.³

CLINICAL DATA

Network Meta-Analysis

Mease et al (2021)¹ and (2023)^2,4 conducted a Bayesian NMA to indirectly compare the relative treatment effect of TREMFYA to other targeted therapies for PsA, including IL-17A inhibitors like ixekizumab and secukinumab, on joint and skin efficacy outcomes and safety in adults (≥18 years of age) with active PsA.

Study Design/Methods

• A systematic literature review was conducted to identify randomized controlled trials (the original search was conducted in October 2018 and subsequently updated in January 2020 to expand the comparator scope) assessing the use of targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) and biologic DMARDs (bDMARDs) in adults with active PsA.¹ 
• The NMA was updated up to February 2021 and an additional hand-search was conducted in July 2021 to include new data and new agents.² 
• The Bayesian NMA was performed to compare treatments on American College of Rheumatology (ACR) 20/50/70 response, change from baseline in van der Heijde-Sharp (vdH-S) score, Psoriasis Area and Severity Index (PASI) 75/90/100 response, and serious adverse events (SAEs).
  • From the primary assessment timepoint of each trial, ACR and PASI data were included, which varied from 12 to 24 weeks.
  • vdH-S data was included from the 24-week timepoint.
  • Regarding SAEs, the latest placebo-controlled timepoint was utilized in this analysis (up to 24 weeks).
• A multinomial probit NMA model for ordinal outcomes was used to compare interventions for ACR and PASI, dichotomous outcomes were used for SAEs, and continuous outcomes were used for vdH-S score.
  • Treatment effects for ordinal and dichotomous outcomes were modeled on the probit scale and log-odds ratio scale, respectively.
    • These treatment effects were transformed to relative risks (RR) using the unweighted average of trial placebo responses.
  • For continuous outcomes, treatment effects were modeled and reported on the mean difference scale.
• SC TREMFYA 100 mg every 8 weeks (Q8W) and comparators (SC TREMFYA 100 mg every 4 weeks (Q4W) and IL-17A inhibitors like ixekizumab 80 mg (every 2 weeks [Q2W], Q4W, and Q4W/Q2W), secukinumab 300 mg, secukinumab 150 mg, and secukinumab 150 mg with no loading dose, were evaluated.^2,4 

Results

• A total of 33 trials (87 citations) evaluating all doses of tsDMARDs and bDMARDs approved by either the Food and Drug Administration (FDA) or European Medicines Agency for treatment of active PsA were included in the NMA analysis.²
• For results specific to ACR 20 response, PASI 90, vdH-S score, and SAEs, see:
  • Figure: Forest Plot With Pairwise Comparisons of TREMFYA Q8W Versus Comparators for ACR20 Response
  • Figure: Forest Plot With Pairwise Comparisons of TREMFYA Q8W Versus Comparators for PASI 90 Response
  • Figure: Forest Plot With Pairwise Comparisons of TREMFYA Q8W Versus Comparators for vdH-S score
  • Figure: Forest Plot With Pairwise Comparisons of TREMFYA Q8W Versus Comparators for Serious Adverse Events.

Real-World Study

Mease et al (2024)³ evaluated treatment persistence in patients with PsA who were newly initiated on SC TREMFYA vs SC IL-17A inhibitors.

Study Design/Methods

• Inclusion criteria:
  • Adult patients (≥18 years of age) with PsA who were initiated on SC TREMFYA or SC IL-17A inhibitors using IQVIA^TM Health Plan Claims Data.
  • The index date was defined as the first date on which SC TREMFYA or SC IL-17A inhibitors (ie, ixekizumab or secukinumab) was initiated between July 14, 2020, and June 30, 2022.
  • Patients who had ≥12 months of continuous health insurance eligibility before the index date.
  • The baseline period was defined as 12 months before the index date on which the patient was diagnosed with PsA based on ≥2 claims for PsA ≥30 days apart and ≥1 prescription claim for a PsA-related medication.
• Exclusion criteria:
  • Patients who had received >1 claim for any of the studied drugs at any time during the period of continuous eligibility before the index date.
  • Patients with potentially confounding rheumatic diseases (eg, ankylosing spondylitis, other inflammatory arthritides, spondyloarthropathies, rheumatoid arthritis, systemic connective tissue disorders, relapsing polychondritis, or unclassified connective tissue disease) in the 12-month baseline period before the index date.
• In the primary analysis, on-label treatment persistence was defined as the absence of treatment discontinuation (based on a gap of 112 days for SC TREMFYA or 56 days for an SC interleukin-17A inhibitor (IL-17Ai) with approved dosing regimens per FDA label.
  • The primary analysis was conducted based on 2 times of the FDA maintenance interval between administrations per label after induction.
• Sensitivity analyses of on-label treatment persistence were performed.
  • In sensitivity analysis 1, on-label treatment persistence was defined as the absence of treatment discontinuation based on 1 time of the FDA maintenance interval between administrations per label after induction (a gap of 56 days for SC TREMFYA or 28 days for an SC IL-17Ai).
  • In sensitivity analysis 2 (fixed gap), on-label treatment persistence was defined as the absence of treatment discontinuation for a fixed gap of 84 days (in order to evaluate persistence based on the same gap definition for all index biologics).
• Weighted Cox proportional hazard models were used to compare on-label persistence through 12 months post-index between the standardized mortality ratio-weighted SC TREMFYA and SC IL-17Ai groups.

Results

Baseline Characteristics

• The SC TREMFYA group (n=910) and the SC IL-17Ai group (n=2743; ixekizumab, n=1010; secukinumab, n=1733) were evaluated during the 12-month baseline period.

Treatment Persistence

• In the primary analysis, the SC TREMFYA group was significantly (~2 times) more likely to persist with treatment at 12 months than the SC IL-17Ai group (hazard ratio [HR], 1.85; 95% confidence interval, 1.60-2.13; P<0.001).
  • In the SC TREMFYA vs SC IL-17Ai group, the on-label persistence at 12 months was 67% vs 50%.
  • The median time to discontinuation was not reached in the SC TREMFYA group and 12.3 months in the SC IL-17Ai group.
• In sensitivity analysis 1, the SC TREMFYA group was ~1.7 times more likely to persist with on-label treatment at 12 months than the SC IL-17Ai group (HR, 1.72; P<0.001).
• In sensitivity analysis 2, the SC TREMFYA group was ~1.2 times more likely to persist with on-label treatment at 12 months than the SC IL-17Ai group (HR, 1.21; P=0.0113).
• On-label persistence at 3, 6, 9, and 12 months is summarized in Table: Primary Analysis (2x Duration) of On-Label Persistence through 12 Months in the Weighted SC TREMFYA and SC IL-17Ai Groups.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 05 December 2024.