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Long-term outcome of patients with steroid-refractory acute severe UC treated with ciclosporin or infliximab.
Laharie, D, Bourreille, A, Branche, J, Allez, M, Bouhnik, Y, Filippi, J, Zerbib, F, Savoye, G, Vuitton, L, Moreau, J, et al
Gut. 2018;67(2):237-243
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Plain language summary
Intravenous steroids are the first-line therapy for ulcerative colitis (UC) patients who are hospitalised during a severe UC flare-up. In the 40% of patients who don’t respond to steroids, the drugs ciclosporin and infliximab have been found to be efficient in preventing surgery to remove part or all of the colon, but there is a lack of data on the long-term outcomes of using these medications in UC patients. The aim of this study was to assess long-term outcome of patients included in a randomised trial comparing ciclosporin and infliximab. Between 2007 and 2010, 115 patients with UC that did not respond to steroids were randomised to receive ciclosporin or infliximab in association with azathioprine. Patients were followed to January 2015 or death. After a median follow-up of 5.4 years, colectomy-free survival rates at 1 and 5 years were, respectively, 70.9% and 61.5% in patients who received ciclosporin and 69.1% and 65.1% in those who received infliximab. Long-term colectomy-free survival was independent from initial treatment. However, a higher proportion of patients initially treated with ciclosporin needed a new treatment compared with those who received infliximab first. The researchers concluded that these results further confirm a similar efficacy and good safety profiles of both drugs.
Abstract
OBJECTIVE Ciclosporin and infliximab have demonstrated short-term similar efficacy as second-line therapies in patients with acute severe UC (ASUC) refractory to intravenous steroids. The aim of this study was to assess long-term outcome of patients included in a randomised trial comparing ciclosporin and infliximab. DESIGN Between 2007 and 2010, 115 patients with steroid-refractory ASUC were randomised in 29 European centres to receive ciclosporin or infliximab in association with azathioprine. Patients were followed until death or last news up to January 2015. Colectomy-free survival rates at 1 and 5 years and changes in therapy were estimated through Kaplan-Meier method and compared between initial treatment groups through log-rank test. RESULTS After a median follow-up of 5.4 years, colectomy-free survival rates (95% CI) at 1 and 5 years were, respectively, 70.9% (59.2% to 82.6%) and 61.5% (48.7% to 74.2%) in patients who received ciclosporin and 69.1% (56.9% to 81.3%) and 65.1% (52.4% to 77.8%) in those who received infliximab (p=0.97). Cumulative incidence of first infliximab use at 1 and 5 years in patients initially treated with ciclosporin was, respectively, 45.7% (32.6% to 57.9%) and 57.1% (43.0% to 69.0%). Only four patients from the infliximab group were subsequently switched to ciclosporin. Three patients died during the follow-up, none directly related to UC or its treatment. CONCLUSIONS In this cohort of patients with steroid-refractory ASUC initially treated by ciclosporin or infliximab, long-term colectomy-free survival was independent from initial treatment. These long-term results further confirm a similar efficacy and good safety profiles of both drugs and do not favour one drug over the other. TRIAL REGISTRATION NUMBER EudraCT: 2006-005299-42; ClinicalTrials.gouv number: NCT00542152; post-results.
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Longitudinal Study of the Psoriasis-Associated Skin Microbiome during Therapy with Ustekinumab in a Randomized Phase 3b Clinical Trial.
Loesche, MA, Farahi, K, Capone, K, Fakharzadeh, S, Blauvelt, A, Duffin, KC, DePrimo, SE, Muñoz-Elías, EJ, Brodmerkel, C, Dasgupta, B, et al
The Journal of investigative dermatology. 2018;138(9):1973-1981
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Chronic plaque psoriasis is an immune-mediated disease of the skin and joints. A growing appreciation of the role of the innate immune system in psoriasis pathogenesis stems from the prominent role of inflammatory cytokines and cells associated with innate immunity in the disease and associations observed between psoriasis and genetic variations involved in innate immunity. The aim of this study was to assess changes of the skin microbiome in the setting of a longitudinal phase 3b study of patients receiving up to 2 years of ustekinumab therapy. Results show that prior to treatment, there were minor, body-site specific differences in microbial diversity and composition when comparing lesional with non-lesional skin. Microbial heterogeneity was greater in lesional skin than non-lesional skin. During ustekinumab treatment, the composition of microbiota diverged further between lesional and non-lesional skin across body sites. The divergence observed between lesional and non-lesional skin during ustekinumab treatment varied by body site. Authors conclude that their findings may help inform future study design and it may also have medically relevant implications for diagnostics and therapeutics involving the skin microbiome.
Abstract
Plaque psoriasis, a chronic inflammatory disease primarily affecting the skin, is thought to have a multifactorial etiology, including innate immune system dysregulation, environmental triggers, and genetic susceptibility. We sought to further understand the role of skin microbiota in psoriasis pathogenesis, as well as their response to therapy. We systematically analyzed dynamic microbiota colonizing psoriasis lesions and adjacent nonlesional skin in 114 patients prior to and during ustekinumab treatment in a phase 3b clinical trial. By sequencing the bacterial 16S ribosomal RNA gene from skin swab samples obtained at six anatomical sites, we identified minor, site-specific differences in microbial diversity and composition between pretreatment lesional and nonlesional skin. During therapy, microbial communities within lesional and nonlesional skin diverged, and body-site dispersion increased, reflecting microbial skin site-specificity. Microbiota demonstrated greater pretreatment heterogeneity in psoriatic lesions than in nonlesional skin, and variance increased as treatment progressed. Microbiota colonizing recurrent lesions did not overlap with pretreatment lesional microbiota, suggesting colonization patterns varied between initial and recurrent psoriatic lesions. While plaque psoriasis does not appear to be associated with specific microbes and/or microbial diversity, this large dataset provides insight into microbial variation associated with (i) disease in different body locations, (ii) initial versus recurrent lesions, and (iii) anti-IL12/23 therapy.