Background/Purpose: This double-blind, randomized study evaluated efficacy, safety and immunogenicity of PF‑06438179/GP1111, a potential infliximab biosimilar, vs infliximab sourced from the EU (infliximab-EU) in patients (pts) with moderate to severe active RA with inadequate response to MTX and ≤2 doses of 1 non-depleting, non-infliximab biologic. We report results after the first 30 wks of treatment.

Methods: Pts (N=650), stratified by geographic region, were randomized 1:1 to PF‑06438179/GP1111 or infliximab-EU (3 mg/kg IV at wks 0, 2, 6 and then every 8 wks), both given with MTX (10-25 mg/wk). Dose escalation to 5 mg/kg was allowed starting at wk 14 for pts with inadequate response. Primary endpoint was ACR20 response rate at wk 14. Secondary efficacy endpoints included ACR20 response rate, Disease Activity Score-28; 4 components based on high-sensitivity C-reactive protein (DAS28-CRP) and other measures of clinical response or remission up to wk 30. Therapeutic equivalence was declared if the 2-sided 95% confidence interval (CI) for the difference between groups in ACR20 at wk 14 was within the symmetric equivalence margin of ±13.5%. A 2-sided 90% CI was also calculated, as requested by the FDA, using the asymmetric equivalence margin of –12.0% to +15.0%.

Results: Pts (80.3% female; 79.4% seropositive) had a mean RA duration of 6.9 yrs; mean baseline DAS28-CRP was 6.0 in both groups. Wk 14 ACR20 response rates in the intent-to-treat population were 62.7% for PF‑06438179/GP1111 and 64.1% for infliximab-EU. Using non-responder imputation for missing data (n=23; 3.5%), the treatment difference was –2.39%; corresponding CIs (95%: –9.92%, +5.11%; 90%: –8.75%, +4.02%) were entirely contained within the pre-specified equivalence margins (symmetric and asymmetric). Response rates through wk 30 were similar, with the ACR20 treatment difference ranging from –5.81% to –0.83% at the specified visits. Mean change in DAS28-CRP from baseline was –2.1 at wk 30 for both groups. ACR50, ACR70 and European League Against Rheumatism (EULAR) response as well as DAS remission (DAS28 <2.6) and ACR/EULAR remission were similar between groups at each study visit. Eighty-three pts each in the PF‑06438179/GP1111 (25.7%) and infliximab-EU (25.5%) groups dose escalated at or after wk 14. Incidences of all-causality treatment-emergent adverse events (57.3% vs 54.0%) and serious adverse events (any event: 5.0% vs 6.1%; infections: 1.9% vs 2.8%) were similar between PF‑06438179/GP1111 and infliximab-EU, respectively. Infusion related reactions (5.9% vs 6.4%), hypersensitivity (13.6% vs 15.6%), pneumonia (0.9% vs 0.9%) and latent/active tuberculosis (0.3% vs 0.3%) were also similar between PF‑06438179/GP1111 and infliximab-EU, respectively. Overall post-dose anti-drug antibody rates through wk 30 were 48.6% for PF‑06438179/GP1111 and 51.2% for infliximab-EU.

Conclusion: PF‑06438179/GP1111 and infliximab-EU showed similar efficacy, safety and immunogenicity in pts with moderate to severe active RA on background MTX. This ongoing trial will evaluate clinical efficacy, safety and immunogenicity after a single transition from infliximab-EU to PF‑06438179/GP1111 after 30 or 54 wks of treatment.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-randomized-double-blind-study-comparing-pf-06438179gp1111-a-potential-infliximab-biosimilar-and-infliximab-both-in-combination-with-mtx-as-treatment-for-patients-with-moderate-to-severe-active/