OP0113 No Increased Incidence of Inflammatory Bowel Disease among Secukinumab-Treated Patients with Moderate To Severe Psoriasis, Psoriatic Arthritis, or Ankylosing Spondylitis: Data from 14 Phase 2 and Phase 3 Clinical Studies

2016 ◽  
Vol 75 (Suppl 2) ◽  
pp. 97.2-98 ◽  
Author(s):  
S. Schreiber ◽  
B.E. Sands ◽  
A. Deodhar ◽  
D. Baeten ◽  
J. Huang ◽  
...  
2019 ◽  
Vol 78 (4) ◽  
pp. 473-479 ◽  
Author(s):  
Stefan Schreiber ◽  
Jean-Frederic Colombel ◽  
Brian G Feagan ◽  
Kristian Reich ◽  
Atul A Deodhar ◽  
...  

ObjectivesHere, we present the reported incidence rates of inflammatory bowel disease (IBD) in patients receiving treatment with secukinumab for psoriasis (PsO), psoriatic arthritis (PsA) or ankylosing spondylitis (AS), in a pooled analysis of 21 clinical trials.MethodsData from all patients who had received at least one dose of secukinumab were included. Safety analyses were conducted to evaluate cumulative IBD rates as well as per-year rates, by indication. Crohn’s disease (CD), ulcerative colitis (UC) and IBD unclassified (IBDU) events were analysed using exposure-adjusted incidence rates (patient incidence rates per 100 patient-years (PY)).ResultsA total of 7355 patients with a cumulative exposure of 16 226.9 PY were included in the pooled analysis. Among 5181 patients with PsO, there were 14 cases of UC, 5 cases of CD and 1 case of IBDU, with exposure adjusted incidence rates (EAIRs) of 0.13, 0.05 and 0.01, respectively. Of these 20 cases, 14 were new-onset. In 1380 patients with PsA, there were 3 cases of UC, 3 cases of CD and 2 cases of IBDU (EAIRs 0.08, 0.08 and 0.05); 7 of these represented new-onset cases. Among 794 patients with AS, there were 4 cases of UC, 8 cases of CD and 1 case of IBDU (EAIRs 0.2, 0.4 and 0.1); 9 were new-onset cases. In the per year analysis, the EAIRs for each indication did not increase over time with secukinumab treatment.ConclusionsIn this pooled secukinumab safety analysis of 7355 patients across 21 clinical trials, cases of IBD events (including CD, UC and IBDU) were uncommon.


2013 ◽  
pp. 189-191
Author(s):  
Norma Marigliano ◽  
Domenico Galasso

Background: Seronegative spondyloarthritis is characterized by the presence of subcutaneous nodules, asymmetrical peripheral arthritis, sacroileitis with or without spondylitis, and rheumatoid-factor negativity. Other common clinical manifestations include oral ulcers, conjunctivitis, and cutaneous lesions such as psoriasis. Familial aggregation has also been described. According to the 1986 classification, corresponding clinical entities include ankylosing spondylitis, psoriatic arthritis, Reiter’s syndrome, arthritis associated with inflammatory bowel disease (IBD), and undifferentiated spondyloarthritis. The disease is also frequently associated with the HLA B27 antigen. From the clinical point of view, there are often incomplete forms of spondyloarthritis, such as reactive arthritis triggered by asymptomatic infections, psoriatic arthritis without psoriasis itself, initial phases of specific forms of spondyloarthritis or the phase of ankylosing spondylitis characterized by sacroiliac lesions, and all forms that remain undifferentiated for long periods of time. Moreover, there are close relations between arthropathy and IBDs, such as Crohn’s disease, ulcerative colitis, and Whipple’s syndrome. Recently, microscopic inflammatory bowel lesions and psoriatic arthritis have been described. Case report: A 30-year-old man (HLA B27-negative) who had been vaccinated against TBC and HBV presented with a 6-year history of recurrent episodes of predominantly left-sided sciatica. The pain was worse at night and during rest. He was suffering from bilateral sacroileitis without spondylitis. Three to five times a day, usually after eating, he passed watery feces containing mucous and small amounts of bright red blood. Colonoscopy revealed pancolitis with histological evidence of chronic inflammation interspersed with areas of acute inflammation, edema, hyperemia, and glandular distortion. One year later, the clinical manifestations and histological findings were essentially unchanged: glandular distortions, chronic and acute inflammation of the lamina propria and crypt microabscesses. There were no granulomas and no evidence of uveitis. The inflammatory index was positive; FR, ENA, ANA titers were negative. He began therapy with adalimumab (loading dose 80 mg followed by 40 mg every 15 days) and mesalazine (2.4 g per os), and the clinical manifestations of the disease improved significantly.


Author(s):  
William J Sandborn ◽  
Brian G Feagan ◽  
Silvio Danese ◽  
Christopher D O’Brien ◽  
Elyssa Ott ◽  
...  

Abstract Background Ustekinumab is currently approved globally in Crohn’s disease (CD) and psoriatic diseases. Recent phase 3 data demonstrate safety/efficacy in ulcerative colitis (UC). Crohn’s disease and UC phase 3 programs had similar study designs, facilitating integrated safety analyses. Methods Data from 6 ustekinumab phase 2/3 CD and UC studies were pooled, and safety was evaluated through 1 year. Patients received 1 placebo or ustekinumab (generally 130 mg or ~6 mg/kg) intravenous induction, then subcutaneous (90 mg) maintenance every 8/12 weeks. Analyses incorporated all patients who received ≥1 ustekinumab dose. Safety outcomes are presented as percentages of patients (induction) and as number of patients with events per 100 patient-years of follow-up (through 1 year). For key safety events, 95% confidence intervals (CIs) are provided, as appropriate. Hazard ratios with 95% CIs from time-to-event analyses for serious adverse events and serious infections were also performed. Results Through 1 year, 2574 patients received ustekinumab (1733 patient-years of follow-up). The number of patients with adverse events per 100 patient-years (placebo 165.99 [95% CI, 155.81–176.67] vs ustekinumab 118.32 [95% CI, 113.25–123.55]), serious AEs (27.50 [95% CI, 23.45–32.04] vs 21.23 [95% CI, 19.12–23.51]), infections (80.31 [95% CI, 73.28–87.84] vs 64.32 [95% CI, 60.60–68.21]), serious infections (5.53 [95% CI, 3.81–7.77] vs 5.02 [95% CI, 4.02–6.19]), and malignancies excluding nonmelanoma skin cancer (0.17 [95% CI, 0.00–0.93] vs 0.40 [95% CI, 0.16–0.83]) were similar between placebo and ustekinumab. Conclusions The safety profile of ustekinumab across the pooled inflammatory bowel disease population through 1 year was favorable and generally comparable to placebo. These data are consistent with the established safety profile of ustekinumab across indications. ClinicalTrials.gov numbers NCT00265122; NCT00771667; NCT01369329; NCT01369342; NCT01369355; NCT02407236.


2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 216-217
Author(s):  
A Sarker ◽  
T Shukla ◽  
A Rostom ◽  
J Sim ◽  
J D McCurdy

Abstract Background Secukinumab is a monoclonal antibody targeting interleukin-17A and is commonly used for managing autoimmune diseases such as, psoriasis, psoriatic arthritis, and ankylosing spondylitis. Prior studies have suggested that anti-IL17 therapy may worsen symptoms in patients with pre-existing inflammatory bowel disease (IBD). However, it remains unclear if secukinumab is associated with new-onset IBD or in provoking a flare of previously quiescent IBD. Aims We evaluated patients referred to our IBD clinic who developed intestinal inflammation after starting secukinumab for the management of autoimmune diseases. Methods We performed a retrospective, observational study at a single tertiary care center between 2017 and 2020. Patients referred to our IBD clinic who developed intestinal inflammation after starting secukinumab were included. We excluded patients with an established pre-existing diagnosis of IBD and patients who had positive stool testing for infectious organisms. Patient demographics, disease characteristics, distribution of intestinal inflammation and clinical outcomes were assessed. The pathology slides were reinterpreted by a single pathologist with a specialty in gastroenterology to determine the histologic characteristics of the inflammation. Results A total of 8 patients developed gastrointestinal symptoms after starting secukinumab: 4 (50%) males with a median age of 42.5 (IQR: 35–50 years old). Secukinumab was initiated for psoriasis in 3 (37.5%) patients, psoriatic arthritis in 2 (25%) patients, ankylosing spondylitis in 2 (25%) patients and juvenile idiopathic arthritis in 1 (12.5%) patient. The median time of onset for gastrointestinal symptoms after starting secukinumab was 7 months (IQR: 4–15 months). Of the patients who underwent testing for inflammatory biomarkers, the median CRP was 25.5 (IQR 25.4–34.2). Endoscopic disease distribution involved the colon in 5 (62.5%) patients and the ileum and colon in 3 (37.5%) patients. In this series of patients, the histologic characteristics demonstrated three patterns of colitis: IBD-like (ulcerative colitis or Crohn’s disease) in 6 (75%) patients based on mucosal granulomas and/or chronic inflammatory changes, MMF-like histology in 1 (12.5%) patient, characterized by an abundance of intraepithelial eosinophils in the lamina propria and numerous crypt apoptotic bodies, and finally active colitis in 1 (12.5%) patient characterized by an absence of chronic mucosal injury or granulomas. The treatment for these patients was cessation of secukinumab and initiating alternative therapies with close clinical monitoring. Conclusions In this small case series, Secukinumab was temporally associated with the development of gastrointestinal inflammation. Further larger studies are required to confirm this association and to determine if IL-17 contributes to the pathogenesis of IBD. Funding Agencies None


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