AB0502 H.P. Acthar® Gel (Repository Corticotropin Injection) as Adjunctive Therapy in Patients with Rheumatoid Arthritis who Have Failed at Least Three Biologic Therapies with Different Modes of Action

Abstract

BackgroundAlthough there are many types of treatment for rheumatoid arthritis (RA) currently available, some patients have disease that is refractory to treatment and thus fail to achieve remission. Acthar Gel may have a potential role in enabling refractory RA patients to reach their treatment goals.ObjectivesTo assess the efficacy and safety of subcutaneous injections of Acthar Gel as adjunctive therapy in patients with active RA.MethodsThis is an ongoing, 17-week, prospective, single-center, open-label study with planned enrollment of 10 patients (≥18 years) with RA, as confirmed by a full count of 68 joints, who are currently not responding sufficiently to a biological agent and have previously inadequately responded to ≥2 biologic agents with different modes of action. Patients are administered 80 U Acthar Gel subcutaneously every 72 hours for 12 weeks, with assessments conducted at screening (Week -1), baseline (Week 0), and Weeks 2, 6, 12, 14, and 16. Primary outcome measures are tender joint count and swollen joint count (ACR Core Data Set 66/68-joint count) and 20-item Health Assessment Questionnaire (HAQ). Secondary outcome measures are acute erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, Patient Global Visual Analogue Scale (VAS), and Physician Global VAS. Disease Activity Score for RA (DAS28) is also being calculated.ResultsSix patients (aged 54-80; 9-39 years since diagnosis of RA) have completed the trial so far. At end of treatment (Week 12), all had reductions from baseline in tender and swollen joint counts; 3 showed improvement in HAQ and 3 showed no change. Improvements in DAS28 (6 of 6 patients), ESR (4/6), CRP (4/6), and Patient (5/6) and Physician (6/6) Global VAS were also seen at end of treatment, with improvements in all measures generally receding 4 weeks post-treatment (Week 16). One patient experienced a mild skin reaction at the injection site, and 1 had hypoglycemic episodes. A third patient was hospitalized for hip pain unrelated to Acthar Gel. All resolved and no patients withdrew from treatment due to adverse events.ConclusionsIt is extremely difficult to provide effective treatment for patients with active RA who have not responded adequately to biological agents with 3 different mechanisms of action. This interim report of an ongoing trial indicates that 80 U Acthar Gel administered subcutaneously every 72 hours for 12 weeks may provide a treatment option for such patients.AcknowledgementsThis study is supported by an investigator-initiated research grant from Autoimmune and Rare Diseases Business (formerly Questcor) Mallinckrodt Pharmaceuticals.Disclosure of InterestT. Gillis Grant/research support from: received study drug and study funding from Autoimmune and Rare Diseases Business (formerly Questcor) Mallinckrodt Pharmaceuticals, M. Crane Grant/research support from: received study drug and study funding from Autoimmune and Rare Diseases Business (formerly Questcor) Mallinckrodt Pharmaceuticals, C. Hinkle Grant/research support from: received study dru...

Industry Payments to Physician Specialists Who Prescribe Repository Corticotropin

“…Among these conditions, controlled clinical trial data only support corticotropin use to treat exacerbations of multiple sclerosis, 18 , 19 although it is no more effective than methylprednisolone. The use of corticotropin for rheumatoid arthritis, 39 dermatomyositis and polymyositis, 40 , 41 , 42 systemic lupus erythematosus, 25 , 43 and nephrotic syndrome 44 , 45 , 46 , 47 , 48 is largely supported by small uncontrolled studies or case series.…”

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

“…Two patients achieved clinical remission, 3 had low disease activity, 3 had moderate disease activity, 1 had high disease activity, and 1 patient terminated treatment early because of lack of efficacy. All 5 patients who received biweekly doses demonstrated a clinical response and showed a structural response of regression of synovitis and regression or nominal change in osteitis Gillis et al [ 35 ] Objective: To assess efficacy and safety of SC injections of RCI as adjunctive therapy in adults with active RA Study design: Prospective, nonrandomized, open-label, single-center trial Treatment: RCI 80 U SC every 72 h for 12 weeks Sample size: 6 Primary outcomes: Tender joint count, swollen joint count, change in 20-item Health Assessment Questionnaire Secondary outcomes: ESR level, CRP, and patient and physician global VAS, change in Disease Activity Score Inclusion criteria: Active RA, not responding sufficiently to ≥2 biologic agents with different modes of action Exclusion criteria: N/A At 12 weeks, all 6 patients had reduced tender and swollen joint counts. Three showed improvement in Health Assessment Questionnaire score and 6 showed improvement in Disease Activity Score.…”

“…RCI is an FDA-approved adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) and for use in “selected cases who may require low-dose maintenance therapy” [ 1 ]. It has been shown to be effective in combination with methotrexate in terms of clinical response, inducing remission and slowing structural changes, with few serious adverse events observed [ 34 , 35 ]. In an open-label study, 10 patients with early RA and at least six tender and swollen joints were treated with methotrexate plus RCI either weekly ( n = 5) or biweekly ( n = 5) [ 34 ].…”

“…In the five patients who received RCI biweekly, both clinical and structural improvements were seen. A second open-label study of RA patients with an inadequate response to two or more biologic agents with different modes of action ( N = 6) found that treatment with RCI for 12 weeks led to reductions in tender and swollen joint counts and improvements in Disease Activity Score for RA (DAS28), Patient Global Visual Analogue Scale (VAS), and Physician Global VAS in all patients [ 35 ].…”

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].…”