Objective Post hoc analyses evaluated the effectiveness and safety of repository corticotropin injection (RCI) in patients with persistently active SLE over 52 weeks.
Methods Patients were initially randomised to 40 U daily or 80 U every other day RCI (n=26) or placebo (n=12) for the 8-week double-blind period. Completers entered the open-label extension (OLE; n=33) receiving 16, 40 or 80 U RCI 1–3 times/week and were followed through week 52. Outcomes included proportion of responders based on a novel index (resolution of joint or skin activity using hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI) without any worsening British Isles Lupus Assessment Group (BILAG) scores in other organ systems) or revised novel index (using SLE Responder Index (SRI) definition of BILAG worsening (1A or 2B)), proportion of responders by SRI and changes in total hSLEDAI and BILAG scores. Adverse events and laboratory values were assessed.
Results At week 52, 12.0% (3/25) RCI/RCI patients and 36.4% (4/11) placebo/RCI patients were responders using the novel index. The revised novel responder index demonstrated response rates of 48.0% (12/25) and 54.5% (6/11) in the RCI/RCI and placebo/RCI groups, respectively. Proportions of SRI responders were 40.0% (10/25) and 54.5% (6/11). In the RCI/RCI group, total hSLEDAI and BILAG scores declined from 10.0 and 15.7 at week 0 to 3.5 and 4.6 at week 52, respectively. Reductions in the placebo/RCI group on switching were observed (mean hSLEDAI: 9.1–3.3; BILAG: 13.5–2.6). Other disease activity endpoints also improved in both groups. No new safety signals were observed during the OLE.
Conclusions RCI demonstrated durable effectiveness in patients with persistently active SLE despite moderate-dose corticosteroid therapy. Switching from placebo resulted in reduced disease activity during the OLE. These data provide the foundation for evaluation of RCI in a robustly powered study.
- clinical research
- systemic lupus erythematosus
- disease activity
- Clinical Trials
This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/
Statistics from Altmetric.com
Contributors RAF and PMB were involved in the design of the study, interpretation and analysis of data, and drafting of the manuscript or revising it for critically important intellectual content. MM and EZ were involved in the interpretation and analysis of data and drafting of the manuscript or revising it for critically important intellectual content. All authors provided final approval of the submitted manuscript and vouch for the completeness and accuracy of the data and data analyses and for the fidelity of the study to the protocol.
Funding Mallinckrodt Pharmaceuticals sponsored this study and provided the study drug, designed the study, conducted the study, collected the data, monitored the conduct of the study and performed statistical analyses in collaboration with the contract research organisation (INC Research, Raleigh, North Carolina, USA) and the external principal and site investigators. The sponsor also provided funding for professional medical writing and editorial assistance.
Competing interests RAF has been a paid consultant to Mallinckrodt Pharmaceuticals as well as the study and a site principal investigator. MM is a paid consultant to Mallinckrodt Pharmaceuticals. EZ is an employee of Mallinckrodt Pharmaceuticals. PMB is an employee of Mallinckrodt Pharmaceuticals and holds stock or stock options in the company.
Patient consent Obtained.
Ethics approval The protocol was approved by the Institutional Review Boards at all participating centres, and the study was conducted according to the principles of the Declaration of Helsinki and Good Clinical Practice.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement No additional data are available.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.