Regina Berkovich1, Rohit Bakshi2, Lilyana Amezcua3, Robert C Axtell4, Steven Y Cen3, Shahamat Tauhid2, Mohit Neema2, Lawrence Steinman5. 1. USC MS Comprehensive Care Center and Research Group, 1520 San Pablo Street, Suite 3000, Los Angeles, CA 90033, USA. 2. Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 3. University of Southern California, Keck School of Medicine, Los Angeles, CA, USA. 4. Oklahoma Medical Research Foundation, Oklahoma City, OK, USA. 5. Stanford University School of Medicine, Stanford, CA, USA.
Abstract
BACKGROUND: The objective of this study was to evaluate monthly intramuscular adrenocorticotropic hormone (ACTH) gel versus intravenous methylprednisolone (IVMP) add-on therapy to interferon β for breakthrough disease in patients with relapsing forms of multiple sclerosis. METHODS: This was a prospective, open-label, examiner-blinded, 15-month pilot study evaluating patients withExpanded Disability Status Scale (EDSS) score 3.0-6.5 and at least one clinical relapse or new T2 or gadolinium-enhanced lesion in the previous year. Twenty-three patients were randomized to ACTH (n = 12) or IVMP (n = 11) and completed the study. The primary outcome measure was the cumulative number of relapses. Secondary outcomes included EDSS, Mental Health Inventory (MHI), plasma cytokines, MS Functional Composite (MSFC), Quality-of-Life (MS-QOL) score, bone mineral density (BMD), and new or worsened psychiatric symptoms per month. Brain magnetic resonance imaging was analyzed post hoc. This was a preliminary and small-scale study. RESULTS:Relapse rates differed significantly [ACTH 0.08, 95% confidence interval (CI) 0.01-0.54 versus IVMP 0.80, 95% CI 0.36-1.75; rate ratio, IVMP versus ACTH: 9.56, 95% CI 1.23-74.6; p = 0.03]. ACTH improved (p = 0.03) MHI (slope 0.95 ± 0.38 points/month; p = 0.02 versus slope -0.38 ± 0.43 points/month; p = 0.39). On-study decreases (all p < 0.05) in eight cytokine levels occurred only in the ACTH group. However, on-study EDSS, MSFC, MS-QOL, BMD, and MRI lesion changes were not significant between groups. Psychiatric symptoms per patient were greater with IVMP than ACTH (0.55, 95% CI 0.12-2.6 versus 0; p < 0.0001). Other common adverse events were insomnia and urinary tract infections (IVMP, seven events each) and fatigue or flu symptoms (ACTH, five events each). CONCLUSIONS: This study provided class II evidence that ACTH produced better examiner-assessed cumulative rates of relapses per patient than IVMP in the adjunctive treatment of breakthrough disease in multiple sclerosis.
RCT Entities:
BACKGROUND: The objective of this study was to evaluate monthly intramuscular adrenocorticotropic hormone (ACTH) gel versus intravenous methylprednisolone (IVMP) add-on therapy to interferon β for breakthrough disease in patients with relapsing forms of multiple sclerosis. METHODS: This was a prospective, open-label, examiner-blinded, 15-month pilot study evaluating patients with Expanded Disability Status Scale (EDSS) score 3.0-6.5 and at least one clinical relapse or new T2 or gadolinium-enhanced lesion in the previous year. Twenty-three patients were randomized to ACTH (n = 12) or IVMP (n = 11) and completed the study. The primary outcome measure was the cumulative number of relapses. Secondary outcomes included EDSS, Mental Health Inventory (MHI), plasma cytokines, MS Functional Composite (MSFC), Quality-of-Life (MS-QOL) score, bone mineral density (BMD), and new or worsened psychiatric symptoms per month. Brain magnetic resonance imaging was analyzed post hoc. This was a preliminary and small-scale study. RESULTS: Relapse rates differed significantly [ACTH 0.08, 95% confidence interval (CI) 0.01-0.54 versus IVMP 0.80, 95% CI 0.36-1.75; rate ratio, IVMP versus ACTH: 9.56, 95% CI 1.23-74.6; p = 0.03]. ACTH improved (p = 0.03) MHI (slope 0.95 ± 0.38 points/month; p = 0.02 versus slope -0.38 ± 0.43 points/month; p = 0.39). On-study decreases (all p < 0.05) in eight cytokine levels occurred only in the ACTH group. However, on-study EDSS, MSFC, MS-QOL, BMD, and MRI lesion changes were not significant between groups. Psychiatric symptoms per patient were greater with IVMP than ACTH (0.55, 95% CI 0.12-2.6 versus 0; p < 0.0001). Other common adverse events were insomnia and urinary tract infections (IVMP, seven events each) and fatigue or flu symptoms (ACTH, five events each). CONCLUSIONS: This study provided class II evidence that ACTH produced better examiner-assessed cumulative rates of relapses per patient than IVMP in the adjunctive treatment of breakthrough disease in multiple sclerosis.
Authors: L Durelli; M R Bongioanni; R Cavallo; B Ferrero; R Ferri; E Verdun; G B Bradac; A Riva; M Geuna; L Bergamini Journal: Mult Scler Date: 1995 Impact factor: 6.312
Authors: Mads Ravnborg; Per Soelberg Sørensen; Magnus Andersson; Elisabeth G Celius; Peter J Jongen; Irina Elovaara; Emmanuel Bartholomé; Cris S Constantinescu; Karsten Beer; Ellen Garde; Bjørn Sperling Journal: Lancet Neurol Date: 2010-06-09 Impact factor: 44.182