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 treatment effect of TREMFYA to other targeted therapies, including tumor necrosis factor inhibitors (TNFis) (golimumab, infliximab, adalimumab, etanercept, and certolizumab pegol), on joint and skin efficacy outcomes and safety in adults with active psoriatic arthritis (PsA).^1,2
• An ongoing ambispective observational cohort study comparing the effectiveness, persistence, and tolerability of second-line subcutaneous (SC) TREMFYA versus (vs) tumor necrosis factor inhibitor (TNFi) in adult patients with PsA after a first-line TNFi.³
• A real-world retrospective study compared the on-label treatment persistence in adult patients with PsA treated with SC TREMFYA vs SC TNFis using the IQVIA PharMetrics^® Plus database.⁴

CLINICAL DATA

Network Meta-analysis

Mease et al (2021)¹ and (2023)² conducted a Bayesian NMA to indirectly compare the treatment effect of TREMFYA with other targeted therapies for PsA, including TNFis (golimumab, infliximab, adalimumab, etanercept, and certolizumab pegol), 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 again 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 and log-odds ratio scales, respectively.
    • These treatment effects were transformed to relative risks using the unweighted averages of trial placebo responses.
  • For continuous outcomes, treatment effects were modeled and reported on the mean difference scale.
• Treatments evaluated pertaining to TREMFYA 100 mg SC every 8 weeks (Q8W) compared to the following TREMFYA dosing regimen and the TNFis: ^2,5
  • TREMFYA 100 mg SC every 4 weeks (Q4W)
  • Intravenous (IV) TNFis (golimumab 2 mg weight-based [WT] and infliximab 5 mg WT)
  • SC TNFis (adalimumab 40 mg, etanercept 25 mg, golimumab 50 mg, and certolizumab 400 mg and 200 mg)

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 (EMA) for the treatment of active PsA were included in the NMA.
• For results specific to multi-ACR20 response, multi-PASI 90 response, vdH-S score, and SAEs, respectively, see:
  • Figure: Forest Plot With Pairwise Comparisons of TREMFYA Q8W vs Comparators for Multi-ACR20 Response.
  • Figure: Forest Plot With Pairwise Comparisons of TREMFYA Q8W vs Comparators for Multi-PASI 90 Response.
  • Figure: Forest Plot With Pairwise Comparisons of TREMFYA Q8W vs Comparators for vdH-S score.
  • Figure: Forest Plot With Pairwise Comparisons of TREMFYA Q8W vs Comparators for SAEs.

Ambispective Study

González-Molina et al (2024)³ reported results from an ambispective, observational cohort study comparing the effectiveness, persistence, and tolerability of second-line SC TREMFYA vs TNFi in patients with PsA after a first-line TNFi. Patient data are sourced from 34 hospitals in Spain.

Study Design/Methods

• An interim analysis was conducted 10 months after the first patient was included in the study.
• Data of 69 patients (SC TREMFYA, n=36; TNFi, n=33) were available at week 12, and data of 39 patients (SC TREMFYA, n=25; TNFi, n=14) were available at week 24. The maximum follow-up period was 24 weeks.

Results

• The proportion of patients achieving Disease Activity in Psoriatic Arthritis (DAPSA) low disease activity (LDA) or remission (≤14) increased with time in both groups (see Table: DAPSA LDA or Remission (≤14) at Week 0, 12, and 24).

• After 24 weeks, 95.7% of patients continued treatment with SC TREMFYA (1 patient discontinued due to patient desire), and 78.3% of patients continued treatment with TNFi (3 patients discontinued due to adverse events and 1 patient discontinued due to primary failure).
• One patient from the SC TREMFYA group reported headache and 4 patients from the TNFi group reported upper respiratory tract infection, syncope, alopecia, and skin reaction. No severe adverse drug reactions were reported.

Retrospective Study

Walsh et al (2024)⁴ compared the on-label treatment persistence in a real-world setting in patients with PsA treated with SC TREMFYA vs SC TNFi using the IQVIA PharMetrics^® Plus database.

Study Design/Methods

• Inclusion criteria:
  • Adult patients with PsA who received index biologic (ie SC TREMFYA 100 mg at baseline, week 4, and Q8W or first SC TNFi [adalimumab, certolizumab pegol, etanercept, or golimumab]) between 14 July 2020 and 31 March 2022 were included.
  • The index date was defined as the date of first claim for SC TREMFYA or SC TNFi.
  • The baseline period was defined as 12 months before the index date in which the patient had a diagnosis for PsA based on ≥2 claims for PsA ≥30 days apart and ≥1 prescription claim for a PsA-related medication.
  • Patients were identified as either biologic-naïve or biologic-experienced based on prior bDMARD use (other than SC TREMFYA, SC TNFi, or IV TNFi) during the
    12-month baseline period.
• Exclusion criteria:
  • Patients had received ≥1 claim for any of the studied drugs at any time during the period of continuous eligibility before the index date.
  • Patients initiated >1 index biologic on the index date or had ≥1 diagnosis for other potentially confounding rheumatic diseases (as listed by the authors) in the baseline period.
• 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 TNFi) or any dose escalation/reduction during follow-up.
• Sensitivity analyses were done for on-label persistence, defined as follows:
  • 1^st sensitivity analysis: absence of treatment discontinuation based on a gap of 56 days for SC TREMFYA or 28 days for an SC TNFi.
  • 2^nd sensitivity analysis: absence of treatment discontinuation for a fixed 112 days to evaluate persistence based on the same gap definition for all index biologics.
• Cox proportional hazard models were used to compare the risk of discontinuation between the standardized mortality ratio-weighted treatment cohorts (SC TREMFYA and SC TNFi groups).

Results

Baseline Characteristics

• The SC TREMFYA group (N=526), 48.5% were biologic naive and the SC TNFi group (N=1953: adalimumab, n=1339; etanercept, n=400; certolizumab pegol, n=159; SC golimumab, n=55), 87.9% were biologic-naive during the 12-month baseline period.
• After implementation of treatment weighting, baseline demographic and clinical characteristics were comparable (except for prior bDMARD use during the baseline period [51.5% in the SC TREMFYA vs 16.7% in the SC TNFi cohort]) across the SC TREMFYA and SC TNFi groups. See Table: Select Demographics and Baseline Characteristics for Weighted Cohort in the 12-Month Baseline Period.

Treatment Persistence

• In the SC TREMFYA vs SC TNFi group, the mean follow-up time was 12.3 vs 12.4 months and the proportion of PsA patients persistent on treatment after 12 months was 72% vs 44%, respectively.
• In the primary analysis, the SC TREMFYA group was 3 times more likely to persist on treatment at 12 months compared with the SC TNFi group (hazard ratio [HR], 2.97; 95% confidence interval [CI], 2.36-3.74; P<0.001).
  • The median time to discontinuation was not reached in the SC TREMFYA group and 8.9 months in the SC TNFi group.
• On-label persistence at 3, 6, 9, and 12 months is summarized in Table: Analysis of On-Label Persistence Through 12 Months in the Weighted TREMFYA and SC TNFi Groups.

• In sensitivity analysis 1, the SC TREMFYA group was 2.4 times more likely to persist on treatment at 12 months compared with the SC TNFi group (HR, 2.41; 95% CI, 1.98-2.92; P<0.001).^4,6
  • The median time to discontinuation was 18.4 months in the SC TREMFYA group and 6.9 months in the SC TNFi group.⁴
• In sensitivity analysis 2, the SC TREMFYA group was 2.4 times more likely to persist on treatment at 12 months compared with the SC TNFi group (HR, 2.35; 95% CI, 1.86-2.97; P<0.001).^4,6
  • The median time to discontinuation was not reached in the SC TREMFYA group and 13.8 months in the SC TNFi group.⁴

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 17 December 2024.