Efficacy and tolerability of repository corticotropin injection in patients with persistently active SLE: results of a phase 4, randomised, controlled pilot study

Abstract

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.

<p>Treatment with Repository Corticotropin Injection in Patients with Rheumatoid Arthritis, Systemic Lupus Erythematosus, and Dermatomyositis/Polymyositis</p>

“…In a Phase 4 pilot study, 38 patients with SLE were randomized 2:1:2:1 to 8 weeks of double-blind, placebo-controlled treatment with RCI (40 or 80 U or volume-matched placebo, once every other day) followed by a 44-week open-label extension phase. 16 While this exploratory study found that numerical differences were not statistically significant in the primary endpoint, a composite responder index, secondary endpoints and post hoc analyses linked RCI treatment to sustained improvements in SLE signs and symptoms and a tolerable safety profile. 16,17 These results supported the design of a wellpowered, ongoing, randomized, double-blind placebocontrolled study (NCT02953821) to evaluate 24 weeks of treatment with RCI in patients with persistently active SLE despite treatment with moderate-dose corticosteroids.…”

“…12 RCI has been used successfully to treat patients with SLE exacerbations not controlled by conventional treatments. [13][14][15][16][17] In the United States, DM has a prevalence of 1 to 6 per 100,000 persons, and PM ranges from the largest fraction with approximately 10 per 100,000 persons in the United States down to the rarest condition that should only be diagnosed by exclusion. 18 Glucocorticoids are used for first-line treatment of patients with DM/PM, followed by (or in conjunction with) immunosuppressive maintenance; in case of intolerance or insufficient response, oral cyclosporine or intravenous immunoglobulin G may be used and, upon relapse or interstitial lung disease, rituximab or cyclophosphamide may be considered.…”

Clinical and Economic Evaluation of Repository Corticotropin Injection: A Narrative Literature Review of Treatment Efficacy and Healthcare Resource Utilization for Seven Key Indications

“…One patient stopped treatment because of heart block. Steroid dose decreased from a median (IQR) of 15 mg at baseline to 1.25 mg at last visit Systemic lupus erythematosus Fiechtner and Montroy [ 44 ] Objective: To assess the efficacy and safety of RCI in reducing the intensity of flares in patients with SLE Study design: Prospective open-label trial Treatment groups: RCI (80 U/mL by SC injection for 10 days, with an optional 5 additional days) Sample size: 10 Primary outcomes: Reduction in flare intensity based on SLEDAI-2 K scores Secondary outcomes: Physician Global Assessment; Patient Global Assessment; Lupus Quality of Life scale; Functional Assessment of Chronic Illness Therapy-Fatigue scale; British Isles Lupus Assessment Group Index scores; and markers of inflammation, including ESR and CRP Inclusion criteria: Diagnosis of SLE with chronic disease activity requiring ongoing treatment or observation for ≥8 weeks, moderately to severely active disease, meet ACR criteria for SLE flare, receipt of prednisone ≤20 mg/day or equivalent for ≥4 weeks or immunosuppressive or antimalarial treatment for SLE for ≥8 weeks Exclusion criteria: Any new prednisone therapy or change in current oral prednisone therapy, receipt of ≥1 prescribed NSAID, or surgery within past 4 weeks; history of allergy or reaction to any component of RCI or live or attenuated vaccine; and others At day 28 there were statistically significant reductions in SLEDAI-2 K scores and improvements in Physician Global Assessment, Patient Global Assessment, Functional Assessment of Chronic Illness Therapy-Fatigue, and erythrocyte sedimentation rate (all p ≤ 0.5) Furie et al [ 45 ] Objective: To evaluate the efficacy of RCI added to standard of care in patients requiring moderate-dose corticosteroids for symptomatic SLE Study design: Prospective, randomized, double-blind, placebo-controlled, phase 4 pilot study Sample size: 38 Treatment: RCI 40 U daily or 80 U every other day or volume-matched placebo gel for 4 weeks, then RCI tapered to twice weekly for 4 weeks Outcomes: Change in composite measure of hybrid SLEDAI (hSLEDAI), BILAG, and CLASI scores, and tender and swollen joint count Inclusion criteria: Persistently active SLE and/or cutaneous involvement (hSLEDAI score >2), moderate to severe rash with arthritis and/or skin involvement and BILAG score of A or B in mucocutaneous and/or musculoskeletal systems despite a stable dose of prednisone for ≥4 weeks Exclusion criteria: Initiation of corticosteroid treatment within previous 2 months; active nephritis or active CNS lupus requiring treatment within previous 3 months, and other criteria At week 8, the proportion of responders was higher in RCI groups (RCI 40 U, 53.8%; RCI 80 U, 33.3%), but difference from placebo (27.3%) was not statistically significant. Statistically significant improvements were seen in the RCI groups for hSLEDAI, BILAG, and CLASI scores Symptomatic sarcoidosis Salomon et al [ 51 ] Objective: To record o...…”

A Retrospective Medical Record Review of Utilization Patterns and Medical Resource Use Associated with Repository Corticotropin Injection among Patients with Rheumatologic Diseases in the United States

“…Recent progress in understanding the effects of RCI in modulating immune responses has led to increased interest in RCI as a therapeutic choice [2]. Clinical trials and retrospective case series have found RCI to be effective for reducing disease activity and signs/symptoms as well as improving functional status in patients with RA, PsA, DM/PM, and SLE [3][4][5][6][7][8][9][10][11][12]. Claims data studies that examined medical resource use (MRU) relating to rheumatologic disorders reported that RCI treatment was associated with reduced health care utilization [13,14].…”