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Real-life effectiveness of ustekinumab in inflammatory bowel disease patients with concomitant psoriasis or psoriatic arthritis: An IG-IBD study

Published:March 20, 2019DOI:https://doi.org/10.1016/j.dld.2019.03.007

      Abstract

      Background

      Few data exist regarding the effectiveness of ustekinumab in inflammatory bowel disease (IBD) patients treated for concomitant psoriasis or psoriatic arthritis.

      Aims

      to describe the outcomes of IBD patients who received subcutaneous ustekinumab through a dermatological or rheumatological prescription.

      Methods

      This multicenter, retrospective study included all IBD patients who were started on ustekinumab for concomitant active psoriasis/ psoriatic arthritis, irrespective of IBD activity. The primary endpoint was overall ustekinumab persistence, defined as the maintenance of therapy because of sustained clinical benefit for IBD.

      Results

      Seventy patients (64 Crohn’s disease / 6 ulcerative colitis) were enrolled. The median follow-up on ustekinumab therapy was 10.7 months (range, 1.4–67.3). Twelve patients (17.1%) withdrew the treatment after a median of 7.4 months (range, 0.9–23.8). The cumulative probability of maintaining ustekinumab treatment was 97.1% at 6 months and 77.1% at 12 months. Among the 56 patients with baseline active IBD, 34 (60.7%) were in clinical remission at the last follow-up visit. Their cumulative probability of achieving clinical remission was 84.7% and 63.9% at 6 and 12 months, respectively. Two patients stopped ustekinumab for an adverse event.

      Conclusions

      Subcutaneous ustekinumab had a good effectiveness profile for IBD patients treated for concomitant dermatological or rheumatological conditions.

      Keywords

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      References

        • Kobayashi T.
        • Okamoto S.
        • Hisamatsu T.
        • et al.
        IL23 differentially regulates the Th1/Th17 balance in ulcerative colitis and Crohn’s disease.
        Gut. 2008; 57: 1682-1719
      1. STELARA® (ustekinumab) Product Monograph. Janssen (http://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/STELARA-pi.pdf).

        • Feagan B.G.
        • Sandborn W.J.
        • Gasink C.
        • UNITI–IM-UNITI Study Group
        • et al.
        Ustekinumab as Induction and Maintenance Therapy for Crohn’s disease.
        N Engl J Med. 2016; 375: 1946-1960
        • Sandborn W.
        • Rutgeerts P.
        • Gasink C.
        • et al.
        Longterm efficacy and safety of ustekinumab for Crohn’s disease: results from IM-UNITI long-term extension through 2 years.
        Aliment Pharmacol Ther. 2018; 48: 65-77
        • Kopylov U.
        • Afif W.
        • Cohen A.
        • et al.
        Subcutaneous ustekinumab for the treatment of anti-TNF resistant Crohn’s disease–the McGill experience.
        J Crohns Colitis. 2014; 8: 1516-1522
        • Khorrami S.
        • Ginard D.
        • Marín-Jiménez I.
        • et al.
        Ustekinumab for the treatment of refractory Crohn’s disease: the Spanish experience in a large multicentre open-label cohort.
        Inflamm Bowel Dis. 2016; 22: 1662-1669
        • Wils P.
        • Bouhnik Y.
        • Michetti P.
        • et al.
        Subcutaneous ustekinumab provides clinical benefit for two-thirds of patients with Crohn’s disease refractory to anti-tumor necrosis factor agents.
        Clin Gastroenterol Hepatol. 2016; 14: 242-250
        • Ma C.
        • Fedorak R.N.
        • Kaplan G.G.
        • et al.
        Clinical, endoscopic and radiographic outcomes with ustekinumab in medically-refractory Crohn’s disease: real world experience from a multicentre cohort.
        Aliment Pharmacol Ther. 2017; 45: 1232-1243
        • Ma C.
        • Fedorak R.N.
        • Kaplan G.G.
        • et al.
        Long-term maintenance of clinical, endoscopic, and radiographic response to ustekinumab in moderate-to-severe Crohn’s disease: real-world experience from a multicenter cohort study.
        Inflamm Bowel Dis. 2017; 23: 833-839
        • Wils P.
        • Bouhnik Y.
        • Michetti P.
        • et al.
        Long-term efficacy and safety of ustekinumab in 122 refractory Crohn’s disease patients: a multicentre experience.
        Aliment Pharmacol Ther. 2018; 47: 588-595
        • Chimenti M.S.
        • Ortolan A.
        • Lorenzin M.
        • et al.
        Effectiveness and safety of ustekinumab in naïve or TNF-inhibitors failure psoriatic arthritis patients: a 24-month prospective multicentric study.
        Clin Rheumatol. 2018; 37: 397-405
        • Iskandar I.Y.
        • Ashcroft D.M.
        • Warren R.B.
        • et al.
        Demographics and disease characteristics of patients with psoriasis enrolled in the British association of dermatologists biologic interventions Register.
        Br J Dermatol. 2015; 173: 510-518
        • Kimball A.B.
        • Leonardi C.
        • Stahle M.
        • PSOLAR Steering Committee
        • et al.
        Demography, baseline disease characteristics and treatment history of patients with psoriasis enrolled in a multicentre, prospective, disease-based registry (PSOLAR).
        Br J Dermatol. 2014; 171: 137-147
        • Pugliese D.
        • Guidi L.
        • Ferraro P.M.
        • et al.
        Paradoxical psoriasis in a large cohort of patients with inflammatory bowel disease receiving treatment with anti-TNF alpha: 5-year follow-up study.
        Aliment Pharmacol Ther. 2015; 42: 880-888
        • Guerra I.
        • Pérez-Jeldres T.
        • Iborra M.
        • et al.
        Incidence, clinical characteristics, and management of psoriasis induced by anti-TNF therapy in patients with inflammatory bowel disease: a nationwide cohort study.
        Inflamm Bowel Dis. 2016; 22: 894-901
        • Tillack C.
        • Ehmann L.M.
        • Friedrich M.
        • et al.
        Anti-TNF antibody-induced psoriasiform skin lesions in patients with inflammatory bowel disease are characterised by interferon-γ-expressing Th1 cells and IL-17A/IL-22-expressing Th17 cells and respond to anti-IL-12/IL-23 antibody treatment.
        Gut. 2014; 63: 567-577
        • Alivernini S.
        • Pugliese D.
        • Tolusso B.
        • et al.
        Paradoxical arthritis occurring during anti-TNF in patients with inflammatory bowel disease: histological and immunological features of a complex synovitis.
        RMD Open. 2018; 4e000667
        • Coates L.C.
        • Kavanaugh A.
        • Mease P.J.
        • et al.
        Group for research and assessment of psoriasis and psoriatic arthritis: treatment recommendations for psoriatic arthritis 2015.
        Arthritis Rheumatol. 2016; 106071
        • Gossec L.
        • Smolen J.S.
        • Ramiro S.
        • et al.
        European league against rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update.
        Ann Rheum Dis. 2016; : 499-510
        • Silverberg M.S.
        • Satsangi J.
        • Ahmad T.
        • et al.
        Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a working party of the 2005 Montreal world congress of gastroenterology.
        Can J Gastroenterol. 2005; : 5-36
        • Harvey R.F.
        • Bradshaw J.M.
        A simple index of Crohn’s-disease activity.
        Lancet. 1980; 1: 514
        • Schroeder K.W.
        • Tremaine W.J.
        • Ilstrup D.M.
        Coated oral 5-aminosalcylic acid therapy for mildly to moderately active ulcerative colitis.
        N Eng J Med. 1987; 317: 1625-1629
        • Gisondi P.
        • Altomare G.
        • Ayala F.
        • et al.
        Italian guidelines on the systemic treatments of moderate-to-severe plaque psoriasis.
        J Eur Acad Dermatol Venereol. 2017; 31: 774-790
        • Coates L.C.
        • Fransen J.
        • Helliwell P.S.
        Defining minimal disease activity in psoriatic arthritis: a proposed objective target for treatment.
        Ann Rheum Dis. 2010; 69: 48-53
        • Allez M.
        • Karmiris K.
        • Louis E.
        • et al.
        Report of the ECCO pathogenesis workshop on anti-TNF therapy failures in inflammatory bowel diseases: definitions, frequency and pharmacological aspects.
        J Crohns Colitis. 2010; 4: 355-366
        • Gisbert J.P.
        • Panés J.
        Loss of response and requirement of infliximab dose intensification in Crohn’s disease: a review.
        Am J Gastroenterol. 2009; 104: 760-767
        • Sands B.E.
        • Sandborn W.J.
        • Panaccione R.
        • et al.
        Safety and efficacy of ustekinumab induction therapy in patients with moderate to severe ulcerative colitis: results from the phase 3 UNIFI study.
        Oral Presentation at ACG. 2018;
        • Sandborn W.J.
        • Sands B.E.
        • Panaccione R.
        • et al.
        Efficacy and safety of ustekinumab as maintenance therapy in ulcerative colitis: week 44 results from UNIFI.
        Oral Presentation at ECCO. 2019;
        • Battat R.
        • Kopylov U.
        • Bessissow T.
        • et al.
        Association between ustekinumab trough concentrations and clinical, biomarker, and endoscopic outcomes in patients with Crohn’s disease.
        Clin Gastroenterol Hepatol. 2017; 15: 1427-1434
        • Adedokun O.J.
        • Xu Z.
        • Gasink C.
        • et al.
        Pharmacokinetics and exposure response relationships of ustekinumab in patients with Crohn’s disease.
        Gastroenterology. 2018; 154: 1660-1671
        • Leonardi C.L.
        • Kimball A.B.
        • Papp K.A.
        • et al.
        PHOENIX 1 study investigators. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1).
        Lancet. 2008; 371: 1665-1674
        • Papp K.A.
        • Langley R.G.
        • Lebwohl M.
        • et al.
        PHOENIX 2 study investigators. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2).
        Lancet. 2008; 371: 1675-1684
        • McInnes I.B.
        • Kavanaugh A.
        • Gottlieb A.B.
        • PSUMMIT 2 Study Group
        • et al.
        Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial.
        Lancet. 2013; 382: 780-789
        • Ritchlin C.
        • Rahman P.
        • Kavanaugh A.
        • PSUMMIT 2 Study Group
        • et al.
        Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial.
        Ann Rheum Dis. 2014; 73: 990-999
        • Papp K.A.
        • Griffiths C.E.
        • Gordon K.
        • et al.
        PHOENIX 1 Investigators; PHOENIX 2 Investigators; ACCEPT Investigators. Long-term safety of ustekinumab in patients with moderate-to-severe psoriasis: final results from 5 years of follow-up.
        Br J Dermatol. 2013; 168: 844-854
        • Kavanaugh A.
        • Puig L.
        • Gottlieb A.B.
        • et al.
        Efficacy and safety of ustekinumab in psoriatic arthritis patients with peripheral arthritis and physician-reported spondylitis: post-hoc analyses from two phase III, multicentre, double-blind, placebo-controlled studies (PSUMMIT-1/PSUMMIT-2).
        Ann Rheum Dis. 2016; 75: 1984-1988