SUMMARY

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• The efficacy and safety of TREMFYA (COSMOS) was evaluated in a randomized, phase 3b, double-blind, placebo-controlled, multicenter trial in patients with active psoriatic arthritis (PsA) with an inadequate response to 1-2 tumor necrosis factor inhibitors (TNFis). The proportion of patients who achieved a response of ≥20% improvement from baseline in the American College of Rheumatology Criteria (ACR20) at week 24 was 44.4% in the TREMFYA 100 mg group and 19.8% in the placebo group (P<0.001) and they maintained response in the TREMFYA group through week 48.¹
• Through week 24, serious adverse events (SAEs) and serious infections occurred in 3.7% and 0.5% of patients, respectively, in the TREMFYA group (n=189). In the placebo group (n=96), SAEs and serious infections occurred in 3.1% and 0% of patients, respectively. Similar safety profile was observed through weeks 24 and 56.¹
• In a post hoc analysis of the COSMOS study, a greater proportion of patients treated with TREMFYA had Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Health Assessment Questionnaire-Disability Index (HAQ-DI), 36-item Short-Form Health Survey Physical Component Summary (SF-36 PCS) response, and Dermatology Life Quality Index (DLQI) 0/1 scores at 24 weeks compared with placebo.²

CLINICAL DATA

COSMOS

Coates et al (2021)¹ evaluated the efficacy and safety of TREMFYA in adult patients with active PsA who demonstrated inadequate response to 1-2 TNFis in a randomized, double-blind, placebo-controlled, multicenter, phase 3b study.

Study Design/Methods

• Select inclusion criteria: patients ≥18 years of age; active PsA for ≥6 months; ≥3 swollen joints and ≥3 tender joints for ≥6 months; patients who met Classification Criteria for Psoriatic Arthritis (CASPAR) at screening; active (≥1 psoriatic plaque of ≥2 cm) or documented history of plaque PsO or current nail PsO; inadequate response or intolerance to 1-2 TNFis.^1,3
• Stable baseline use of medications, including methotrexate (MTX), sulfasalazine (SSZ), hydroxychloroquine (HCQ), leflunomide (LEF), oral corticosteroids, and nonsteroidal anti-inflammatory drugs (NSAIDs) or other analgesics were permitted.
• Patients were randomized in a 2:1 ratio to receive either TREMFYA 100 mg or placebo subcutaneously (SC) at weeks 0, 4, and every 8 weeks (q8w) thereafter through week 44.
• The study comprised placebo-controlled (weeks 0-24) and active-treatment (weeks 24-48) periods, with final study intervention at week 44.
• At week 16, patients from either group who experienced <5% improvement from baseline in both swollen and tender joint counts were eligible for early escape (EE) to initiate/increase one of the permitted concomitant medications per investigator discretion. Patients in the TREMFYA group continued the randomized treatment and received placebo at week 16 to maintain blinding, and patients in the placebo group who qualified for EE received TREMFYA at weeks 16, 20, and q8w thereafter through week 44.
• At week 24, all remaining randomized placebo patients crossed over to receive TREMFYA 100 mg at weeks 24, 28, and q8w thereafter through week 44.³
• The primary endpoint was an ACR20 response at week 24.
  • Patients with missing data or who met treatment failure (TF) criteria through week 24 (defined as discontinuation of study agent and/or study participation for any reason, initiation or increase in the dose of allowed conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or oral corticosteroids for PsA, and initiation of protocol-prohibited medications/therapies for PsA or met EE criteria) were considered nonresponders.
  • In the EE-correction analysis, 12 patients in the TREMFYA group did not meet any other TF criteria (ie, introduction/change in the dose of concomitant therapy) through week 24, and their response was included with other patients in the TREMFYA group; 8 patients in the placebo group received TREMFYA as EE therapy at weeks 16 and 20, met TF criteria, and were considered nonresponders.
• Efficacy response was assessed through week 48.
• Multiplicity-controlled secondary endpoints evaluated at week 24 included the following: mean change from baseline in HAQDI; ≥50% improvement from baseline in the American College of Rheumatology Criteria (ACR50); mean change from baseline in the SF-36 PCS score; and 100% improvement from baseline in the Psoriasis Area and Severity Index (PASI 100) score in patients with ≥3% body surface area (BSA) psoriatic involvement and an Investigator’s Global Assessment (IGA) score ≥2 at baseline.
• Through week 56, safety was evaluated as events per 100 PY.
• Through week 44, 88% of patients treated with TREMFYA 100 mg completed the study.

Results

Patient Characteristics

• Overall, 285 patients were randomized to receive TREMFYA 100 mg (n=189) or placebo (n=96).
• Baseline demographics are summarized in Table: Summary of Patient Baseline Demographics.

Efficacy

• At week 4, the ACR20 response was significantly higher in the TREMFYA group vs the placebo group (19.0% vs 4.2%; P<0.001; not multiplicity adjusted), with TF criteria applied.
• At week 24, the primary endpoint for ACR20 response rates were 44.4% (84/189) vs 19.8% (19/96) for the TREMFYA vs placebo group (P<0.001).
• ACR20 response rates for TREMFYA vs placebo were consistent across subgroups defined by baseline patient and disease characteristics (gender, body weight, swollen joint count, tender joint count, C-reactive protein, enthesitis, and dactylitis) and by prior and concomitant medications (nbDMARDs, oral corticosteroids, NSAIDs, prior TNFis, reason for prior TNFi discontinuation). See Table: ACR20 Response at Week 24 by Baseline Characteristics.

• The results for the primary and secondary endpoints are summarized in Table: Summary of Primary and Select Secondary Endpoints at Week 24 and Week 48.

Safety

• The most common AEs in patients treated with TREMFYA through week 24 included nasopharyngitis (5%) and upper respiratory tract infection (4%), with similar incidence in the placebo group (5% and 3%, respectively).
• Through week 24, SAEs and serious infections occurred in 3.7% and 0.5% of patients in the TREMFYA group (n=189), respectively. In the placebo group (n=96), SAEs and serious infections occurred at 3.1% and 0%, respectively.
• Overall, the safety profile was similar through weeks 24 and 56, with no opportunistic infections, active tuberculosis, anaphylactic/serum sickness-like reaction, confirmed inflammatory bowel disease, or death was reported.
• Through week 56, there was no increase in adverse event rates in the TREMFYA group.³
• The safety results are presented in Table: Summary of Safety Results through Week 56.

Gossec et al (2023)² conducted a post hoc analysis of COSMOS to assess the effect of TREMFYA on minimal clinically important improvement (MCII) and patient-reported outcomes (PROs) in patients with active PsA and inadequate response to 1-2 TNFis.

Study Design/Methods

• The PROs assessed were FACIT-F (≥4-point improvement), HAQ-DI (≥0.35-point improvement), DLQI 0/1 (in patients with DLQI >1, PsO BSA ≥3%, and IGA ≥2 at baseline), and SF-36 PCS score (≥5-point improvement).
• TREMFYA was compared with placebo using logistic regression, adjusting for baseline PRO levels, number of prior TNFis used, and concomitant csDMARDs. Missing data and patients meeting TF criteria were assessed through nonresponder imputation.

Results

Patient Characteristics

• Select baseline characteristics are summarized in Table: Select Baseline Patient Characteristics.

Efficacy

• Results of the FACIT-F, HAQ-DI, DLQI 0/1, and SF-36 PCS responses are summarized in Table: FACIT-F, HAQ-DI, DLQI 0/1, and SF-36 PCS Response Achievement through Week 48.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 04 October 2024.