Multiple infliximab biosimilar switches appear to be safe and effective in a real-world inflammatory bowel disease cohort.

BACKGROUND: Switching from originator infliximab (IFX) to biosimilar IFX is effective and safe. However, data on multiple switching are scarce. The Edinburgh inflammatory bowel disease (IBD) unit has undertaken three switch programmes: (1) Remicade to CT-P13 (2016), (2) CT-P13 to SB2 (2020), and (3) SB2 to CT-P13 (2021). OBJECTIVE: The primary endpoint of this study was to assess CT-P13 persistence following switch from SB2. Secondary endpoints included persistence stratified by the number of biosimilar switches (single, double and triple), effectiveness and safety. METHODS: We performed a prospective, observational, cohort study. All adult IBD patients on IFX biosimilar SB2 underwent an elective switch to CT-P13. Patients were reviewed in a virtual biologic clinic with protocol driven collection of clinical disease activity, C-reactive protein (CRP), faecal calprotectin (FC), IFX trough/antibody levels, and drug survival. RESULTS: 297 patients (CD n = 196 [66%], ulcerative colitis/inflammatory bowel disease unclassified n = 101, [34%]) were switched (followed-up: 7.5 months [6.8-8.1]). This was the third, second and first IFX switch for 67/297 (22.5%), 138/297 (46.5%) and 92/297 (31%) of the cohort respectively. 90.6% of patients remained on IFX during follow-up. The number of switches was not independently associated with IFX persistence after adjusting for confounders. Clinical (p = 0.77), biochemical (CRP ≤5 mg/ml; p = 0.75) and faecal biomarker (FC<250 µg/g; p = 0.63) remission were comparable at baseline, week 12 and week 24. CONCLUSION: Multiple successive switches from IFX originator to biosimilars are effective and safe in patients with IBD, irrespective of the number of IFX switches.

Antibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in inflammatory bowel disease patients treated with infliximab and vedolizumab.

Anti tumour necrosis factor (anti-TNF) drugs increase the risk of serious respiratory infection and impair protective immunity following pneumococcal and influenza vaccination. Here we report SARS-CoV-2 vaccine-induced immune responses and breakthrough infections in patients with inflammatory bowel disease, who are treated either with the anti-TNF antibody, infliximab, or with vedolizumab targeting a gut-specific anti-integrin that does not impair systemic immunity. Geometric mean [SD] anti-S RBD antibody concentrations are lower and half-lives shorter in patients treated with infliximab than vedolizumab, following two doses of BNT162b2 (566.7 U/mL [6.2] vs 4555.3 U/mL [5.4], p <0.0001; 26.8 days [95% CI 26.2 - 27.5] vs 47.6 days [45.5 - 49.8], p <0.0001); similar results are also observed with ChAdOx1 nCoV-19 vaccination (184.7 U/mL [5.0] vs 784.0 U/mL [3.5], p <0.0001; 35.9 days [34.9 - 36.8] vs 58.0 days [55.0 - 61.3], p value < 0.0001). One fifth of patients fail to mount a T cell response in both treatment groups. Breakthrough SARS-CoV-2 infections are more frequent (5.8% (201/3441) vs 3.9% (66/1682), p = 0.0039) in patients treated with infliximab than vedolizumab, and the risk of breakthrough SARS-CoV-2 infection is predicted by peak anti-S RBD antibody concentration after two vaccine doses. Irrespective of the treatments, higher, more sustained antibody levels are observed in patients with a history of SARS-CoV-2 infection prior to vaccination. Our results thus suggest that adapted vaccination schedules may be required to induce immunity in at-risk, anti-TNF-treated patients.

British Society of Gastroenterology guidance for management of inflammatory bowel disease during the COVID-19 pandemic.

The COVID-19 pandemic is putting unprecedented pressures on healthcare systems globally. Early insights have been made possible by rapid sharing of data from China and Italy. In the UK, we have rapidly mobilised inflammatory bowel disease (IBD) centres in order that preparations can be made to protect our patients and the clinical services they rely on. This is a novel coronavirus; much is unknown as to how it will affect people with IBD. We also lack information about the impact of different immunosuppressive medications. To address this uncertainty, the British Society of Gastroenterology (BSG) COVID-19 IBD Working Group has used the best available data and expert opinion to generate a risk grid that groups patients into highest, moderate and lowest risk categories. This grid allows patients to be instructed to follow the UK government's advice for shielding, stringent and standard advice regarding social distancing, respectively. Further considerations are given to service provision, medical and surgical therapy, endoscopy, imaging and clinical trials.