ObjectiveTo evaluate the efficacy of a prolonged-release formulation of a porcine adrenocorticotropic hormone analogue (repository corticotropin injection (RCI)) added to standard of care in patients requiring moderate-dose corticosteroids for symptomatic SLE.MethodsThis prospective, randomised, double-blind, phase 4, pilot study (NCT01753401) enrolled 38 patients with persistently active SLE involving skin and/or joints. Enrolled patients received RCI, 40 U daily or 80 U every other day, or volume-matched placebo gel, for 8 weeks, with dose tapering to twice weekly during weeks 5–8. Efficacy endpoints included proportion of responders at week 4 based on a novel composite measure that included resolution of rash or arthritis measured using the hybrid SLE Disease Activity Index (hSLEDAI) without worsening British Isles Lupus Assessment Group (BILAG) scores in other organ systems at week 4 (primary), as well as improvements in total hSLEDAI and BILAG scores and other measures of skin and joint disease activity over the 8-week treatment period.ResultsResponse, as defined for the primary endpoint, did not differ significantly between the combined placebo and RCI-treated groups at week 4. At week 8, the proportion of responders was higher in RCI-treated patients but did not statistically differ between groups (RCI 40 U (53.8%), RCI 80 U (33.3%), combined placebo (27.3%)). However, RCI treatment was associated with statistically significant improvements in several secondary endpoints, including total hSLEDAI, total BILAG and Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity scores within 8 weeks. Treatment was well tolerated.ConclusionsAlthough the primary endpoint was not met in this pilot study, secondary and post hoc analyses suggested that RCI was associated with improvements in SLE disease activity in a select patient population with steroid-dependent persistent disease.Trial registration numberNCT01753401; results.

Objective. To develop guidelines for therapeutic trials designed to improve the overall course of systemic sclerosis (SSc), that is, to reduce the development of significant organ damage or death.Methods. A committee developed general guidelines for patient inclusion and exclusion criteria, randomization, blinding of patients and physicians, controls, duration of the trial, investigator training, responses, samples size, study dropouts, statistical analyses, data management, and safety monitoring. Delphi and nominal group techniques were used.Results. Briefly, patients with diffuse cutaneous SSc of less than 24 months' duration should be included

ObjectivePost hoc analyses evaluated the effectiveness and safety of repository corticotropin injection (RCI) in patients with persistently active SLE over 52 weeks.MethodsPatients 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.ResultsAt 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.ConclusionsRCI 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.

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