Objectives The level of detail included when describing nailfold videocapillaroscopy (NVC) methods varies among research studies, making interpretation and comparison of results challenging. The overarching objective of the present study was to seek consensus on the reporting standards in NVC methodology for clinical research in rheumatic diseases and to propose a pragmatic reporting checklist. Methods Based on the items derived from a systematic review focused on this topic, a three-step web-based Delphi consensus on minimum reporting standards in NVC was performed among members of the European League against Rheumatism (EULAR) Study Group on Microcirculation in Rheumatic Diseases and the Scleroderma Clinical Trials Consortium. Results A total of 319 articles were selected by the systematic review, and 46 items were proposed in the Delphi process. This Delphi exercise was completed by 80 participants from 31 countries, including Australia and countries within Asia, Europe, North America and South America. Agreement was reached on items covering three main areas: patient preparation before NVC (15 items), device description (5 items) and examination details (13 items). Conclusion Based on the available evidence, the description of NVC methods was highly heterogeneous in the identified studies and differed markedly on several items. A reporting checklist of 33 items, based on practical suggestions made (using a Delphi process) by international participants, has been developed to provide guidance to improve and standardize the NVC methodology to be applied in future clinical research studies.

Background Comparative effectiveness trials using suitable endpoints are necessary to demonstrate therapeutic equivalence of biosimilar molecules. Objectives This phase 3 double-blind, active comparator, clinical trial compared the efficacy and safety of a biosimilar infliximab (IFX), BOW015, to innovator IFX (iIFX). Methods 189 subjects with active rheumatoid arthritis (RA) diagnosed according to the 2010 ACR/EULAR criteria, on stable doses of oral methotrexate (MTX) 10-20 mg/wk, were randomized 2:1 to receive either BOW015 or iIFX 3 mg/kg iv on wks 0, 2, 6, and 14. Subjects had CRP ≥10 mg/L at screening and were tested for TB by PPD, QuantiFERON-TB Gold, and chest radiographs. The primary endpoint was ACR20 response at Wk 16, within a 23% equivalence margin. Responders to BOW015 were continued on treatment and responders to iIFX were crossed over to BOW015 during an open-label phase in which all subjects are being treated every 8 wks through Wk 46. Efficacy and safety were assessed at each visit and immunogenicity at Wks 0 and 14. Twelve subjects were not included in the per protocol (PP) analysis due to study drug discontinuation prior to Wk 16 (n=9), dosing error (n=2) or missing data (n=1). In serum from each patient, antibodies to IFX were assayed using sensitive bridge ELISAs against BOW015 and iIFX. Results The ACR20 responses at Wk 16 for BOW015 and iIFX, respectively, were 89.9% and 86.4% in the PP population (95% CI for the difference, -6.9% to 13.7%) and 85.0% and 85.5% in the intention-to-treat (ITT) population (95% CI for the difference, -11.2% to 10.3%). Kinetics of the ACR20 response was similar for both treatments over the first 16 wks of the trial in both the PP and ITT populations. The maximum treatment difference for the PP population was 3.4% and that for the ITT population was 6.4%, each at Wk 2. Overall, 43.3% of BOW015-treated and 50.0% of iIFX-treated subjects had at least one treatment emergent adverse event (AE). There was no significant difference in AE incidence by body system. Infectious AEs occurred in 15.8% of BOW015-treated and 9.7% of iIFX-treated subjects (p=0.368). Anti-IFX antibodies were detected in 22.1% of BOW015-treated and 35.5% of iIFX-treated subjects at Wk 14 (p=0.055). There was high concurrence between the BOW015-specific and iIFX-specific immunoassays among all subjects, regardless of treatment (κ=0.96). Conclusions This is the first clinical trial of a biosimilar IFX to demonstrate and report the kinetics of response to treatment prior to the plateau phase. The comparable proportion of responders at each of these early time points and at the Wk 16 primary endpoint provides convincing evidence of therapeutic equivalence. The high ACR20 response rates are consistent with those observed in other RA clinical trials in which patients had not failed MTX and were all treated with an active drug. Disclosure of Interest J. Kay Grant/research support: AbbVie Inc.; Eli Lilly and Company; Roche Laboratories, Inc., Consultant for: Amgen Inc.; AbbVie Inc.; Bristol-...

No abstract

BackgroundBOW015 is being developed as a biosimilar of reference infliximab (rIFX, Remicade®). Therapeutic equivalence of BOW015 and rIFX was evaluated in patients with active rheumatoid arthritis (RA) in a 54-week (wk) Phase 3 comparative effectiveness study. ACR20 responses and safety and immunogenicity data have been reported.1,2 Here, we report the secondary efficacy endpoints for this study.ObjectivesTo determine whether efficacy of BOW015 is equivalent to that of rIFX when each is administered in combination with methotrexate (MTX).MethodsIn this double-blind (DB), active comparator study, 189 patients with RA (87.8% female; mean age, 44.8 years) receiving stable MTX doses (10-20 mg/wk) were randomized 2:1 to receive either BOW015 or rIFX 3 mg/kg IV at wks 0, 2, 6 and 14. In the open-label (OL) phase, responders to BOW015 or rIFX (n=157) received BOW015 3 mg/kg IV every 8 wks at wks 22, 30, 38 and 46, with follow-up at wk 54. ACR20/50/70 responses, CRP, ESR, tender and swollen joint counts, subject pain assessment and subject and physician global assessment of disease activity (each by VAS 0-10 cm) were evaluated at multiple time points.ResultsBaseline values were similar for subjects in both treatment arms. At the end of the DB phase (wk 16), BOW015 and rIFX each produced clinically significant improvement from baseline in all secondary endpoints (see table). There was no significant difference in the proportion of subjects achieving ACR20, 50, or 70 responses between treatment groups; these remained stable throughout the OL phase, demonstrating long-term durability of the response to BOW015, including that for the rIFX responders who switched to BOW015 at wk 22. At the end of the OL phase (wk 54), mean improvements in CRP, ESR, and tender and swollen joint counts were similar to those obtained at wk 16 and again did not differ significantly between treatment arms, supporting durability of response. Mean VAS scores for subject pain assessment and for both subject and physician global assessment also did not differ significantly between treatment arms at wk 54 and were lower than those reported at wk 16, consistent with further improvement during the OL phase.ConclusionsEfficacy of BOW015 and rIFX are equivalent, as assessed at wk 16 both by the primary endpoint of ACR20 and by secondary efficacy outcomes. Durability of response to BOW015 has been demonstrated over 54 wks. Taken in combination with analytical, pharmacokinetic, and safety data, these results establish biosimilarity between BOW015 and rIFX.ReferencesKay J et al. Ann Rheum Dis 2014; 73(Suppl2):64.Kay J et al. Arthritis Rheumatol. 2014; 66(12):3538.AcknowledgementsThis research was sponsored by EPIRUS Biopharmaceuticals Inc.Disclosure of InterestJ. Kay Grant/research support from: AbbVie Inc.; Eli Lilly and Company; Pfizer Inc.; Roche Laboratories, Inc. (paid to the University of Massachusetts Medical School), Consultant for: Amgen, Inc.; AbbVie Inc.; AstraZeneca; Boehringer Ingelheim GmbH; Bristol-Myers Squibb Company; Eli Lilly and Company; Ep...