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LINKED CONTENT: This article is linked to Bokemeyer et al paper. To view this article, visit https://doi.org/10.1111/apt.17616 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Strande et al papers. To view these articles, visit https://doi.org/10.1111/apt.18097 and https://doi.org/10.1111/apt.18156. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Strande et al papers. To view these articles, visit https://doi.org/10.1111/apt.18097 and https://doi.org/10.1111/apt.18187. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Casanova et al and Pugliese & Armuzzi papers. To view these articles, visit https://doi.org/10.1111/apt.16361 and https://doi.org/10.1111/apt.16385 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Casanova et al papers. To view these articles, visit https://doi.org/10.1111/apt.16361 and https://doi.org/10.1111/apt.16406 [ABSTRACT FROM AUTHOR]

Summary: Background: Biologics and small molecules for inflammatory bowel disease (IBD) may increase infection risk. Herpes zoster causes acute and long‐term symptoms, but vaccination is not recommended in patients with IBD, unless >50 years of age. Aims: To examine risk of Herpes zoster infection with all licensed biologics and small molecules for IBD using network meta‐analysis. Methods: We searched the literature to 4th October 2022, for randomised controlled trials of these drugs in luminal Crohn's disease or ulcerative colitis reporting data on occurrence of Herpes zoster infection during follow‐up. We used a frequentist approach and a random effects model, pooling data as relative risks (RRs) with 95% confidence intervals (CIs). Results: We identified 25 trials (9935 patients). Only tofacitinib 10 mg b.d. (RR = 6.90; 95% CI 1.56–30.63, number needed to harm (NNH) = 97; 95% CI 19–1022) and upadacitinib 45 mg o.d. (RR = 7.89; 95% CI 1.04–59.59, NNH = 83; 95% CI 10–14,305) were significantly more likely to increase risk of Herpes zoster infection. Janus kinase inhibitors were the most likely drug class to increase risk of infection, and risk increased with higher doses (RR with lowest dose = 3.16; 95% CI 1.02–9.84, NNH = 265; 95% CI 65–28,610, RR with higher dose = 5.91; 95% CI 2.21–15.82, NNH = 117; 95% CI 39–473). Conclusions: In a network meta‐analysis, the janus kinase inhibitor tofacitinib, and all janus kinase inhibitors considered as a class, were most likely to increase risk of Herpes zoster infection. Risk increased with higher doses. [ABSTRACT FROM AUTHOR]

Summary: Background: Anti‐drug antibodies are associated with treatment failure to anti‐TNF agents in patients with inflammatory bowel disease (IBD). Aim: To assess whether immunogenicity to a patient's first anti‐TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence Methods: We conducted a UK‐wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti‐TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti‐TNF agent, defined at any timepoint as an anti‐TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab. Results: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27–3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46–4.80, p < 0.001). For each 10‐fold increase in anti‐infliximab and anti‐adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38–2.17, p < 0.001) and 1.99 (95%CI 1.34–2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39–4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti‐TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure. Conclusion: Irrespective of drug sequence, immunogenicity to the first anti‐TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure. [ABSTRACT FROM AUTHOR]

Summary: Background: The use of biologics poses a moderate to high risk for hepatitis B virus reactivation (HBVr) in chronic carriers. Aim: To determine the prevalence of HBVr with TNF alpha inhibitors, ustekinumab and vedolizumab Method: We followed the MOOSE guidelines and conducted a comprehensive literature search. We conducted a systematic search of EMBASE (Ovid), MEDLINE (Ovid) and PubMed. The studies included patients who were chronic and occult HBV carriers with various rheumatological, dermatological or gastroenterological conditions. We used a random effects model using pooled estimates (prevalence of HBVr with 95% confidence intervals (CI)). Results: We included 29 studies with 1409 patients infected with HBV. The prevalence of HBVr in chronic carriers of HBV was 17.1% (95% CI: 7.0–35.9, n = 5), 16.6% (95% CI: 9.5–27.5%, n = 6), 40.5% (95% CI: 20.3–64.5%, n = 4) and 19.1% (95% CI: 7.3–41.2%, n = 2), respectively, for adalimumab, etanercept, infliximab and ustekinumab. The respective prevalence for reactivation in patients with occult HBV infection was 5.0% (95% CI: 2.8–8.7%, number of studies: n = 18), 2.6% (95% CI: 1.4–4.7%, n = 18), 4.4% (95% CI: 2.2–8.7%, n = 12) and 6.4% (95% CI: 2.2–16.8, n = 5). There were 39 HBVr (26 in chronic HBV and 13 in the occult group) without any hepatic failure or death. In the chronic HBVr group, only three of 24 patients received antiviral prophylaxis. Conclusions: HBVr prevalence rates differ between the chronic carrier state and the occult carrier state. The uptake of prophylactic antiviral therapy in high‐risk groups was low, contrary to clinical practice guidelines. [ABSTRACT FROM AUTHOR]

Summary: Background: Biologicals represent the cornerstone of treatment for moderate‐to‐severe inflammatory bowel diseases (IBD). Many patients cycle between biologicals when encountering loss of response or adverse events. Aim: To assess the occurrence of serious infections and malignancies with exposure to several (classes of) biologicals. Methods: We performed a retrospective cohort study in a tertiary referral centre including consecutive IBD patients exposed to adalimumab, infliximab, ustekinumab or vedolizumab between 1996 and 2019. All serious infections and malignancies, as well as potential confounders, were accounted for. Results: In total, 1575 patients were included with a median (interquartile range) follow‐up of 10 (6–16) years and a duration of biological therapy of 71 (39–112) months. Incidence rates of serious infections were 3.4 per 100 patients' years (PY) in the post‐biological setting. Serious infections after biological exposure were associated with systemic steroids in monotherapy (hazard ratio 2.96 [95% confidence interval 1.78–4.93], p < 0.0001), combination therapy of systemic steroids and a biological (2.44 [1.37–4.34], p = 0.002), female gender (1.25 [1.04–1.51], p = 0.02), and prior serious infections in the pre‐biological setting (1.42 [1.03–1.96], p = 0.03). Malignancy rates were 1.06 per 100PY in the post‐biological setting and increased with older age at biological initiation (1.04 [1.02–1.05], p < 0.0001). The risk for serious infections or malignancies was independent of type and number of biologicals to which the patient was exposed. Conclusion: This study shows that the sequential use of biological therapy in IBD does not seem to convey an overall higher risk of serious infections or malignancies, but that underlying more refractory disease seems to increase this risk. [ABSTRACT FROM AUTHOR]

Summary: Background: Knowledge of the cost of illness of inflammatory bowel disease (IBD) is essential for health policy makers worldwide. Aim: To assess the cost of illness of IBD from the societal perspective taking into account time trends and geographical differences. Methods: A systematic review of all population‐based studies on cost of illness of IBD published in Embase, Medline, Web of Science and Google Scholar. Methodology of included studies was assessed and costs were adjusted to 2018 US dollars. Results: Study methodologies differed considerably, with large differences in perspective, valuation method and population. For prevalent Crohn's disease (CD) cases in the last ten years annual healthcare costs were in Asia $4417 (range $1230‐$31 161); Europe $12 439 ($7694‐$15 807) and North America $17 495 ($14 454‐$20 535). For ulcerative colitis (UC), these were $1606 ($309‐$14 572), $7224 ($3228‐$9779) and $13 559 ($13 559‐$13 559). The main cost driver was medication, the cost of which increased considerably between 1985 and 2018, while outpatient and inpatient costs remained stable. IBD had a negative impact on work productivity. Annual costs of absenteeism for CD and UC were in Asia (with presenteeism) $5638 ($5638‐$5638) and $4828 ($4828‐$4828); Europe $2660 ($641‐$5277) and $2394 ($651‐$5992); North America $752 ($307‐$1303) and $1443 ($85‐$2350). Conclusion: IBD societal cost of illness is increasing, driven by growing costs of medication, and varies considerably between continents. While biologic therapy was expected to decrease inpatient costs by reducing hospitalisations and surgery, these costs have not declined. [ABSTRACT FROM AUTHOR]

Summary: Background: Biological therapies have improved the care of patients with ulcerative colitis (UC). Tofacitinib, an oral small‐molecule Janus kinase inhibitor, is potentially a new treatment option. Aim: To comparatively assess efficacy and harm of tofacitinib and biologics (infliximab, adalimumab, golimumab and vedolizumab) in adult patients not previously exposed to TNF antagonists. Methods: We performed a comprehensive search of PubMed, Embase, Scopus, clinical trial registries, regulatory authorities' websites and major conference proceedings, through August 2017, to identify randomised, placebo‐controlled or head‐to‐head trials assessing tofacitinib or biologics as induction and/or maintenance therapy in moderate‐to‐severe UC. Two reviewers independently extracted study data and outcomes, and investigated each trial's risk‐of‐bias. We used conventional meta‐analysis to synthesise direct evidence, and network meta‐analysis for adjusted indirect treatment comparisons. Results: Fifteen randomised, double‐blind, placebo‐controlled trials (n = 3130) contributed data for induction: All treatments are superior to placebo. Indirect treatment comparisons showed that infliximab is better than adalimumab (OR: 2.01, 95% CI: 1.36‐2.98) and golimumab (1.67, 1.08‐2.59) in clinical response, better than adalimumab (2.10, 1.21‐3.64) in clinical remission, and better than adalimumab (1.87, 1.26‐2.79) and golimumab (1.75, 1.13‐2.73) in mucosal healing. No indirect comparisons between tofacitinib and biologics reached statistical significance. Nine studies (n = 1776) contributed maintenance data showing that all treatments have higher clinical efficacy than placebo. Safety analyses indicated no increased rates of adverse events for the treatments under evaluation (except for infliximab), while vedolizumab may have an advantage regarding the occurrence of serious adverse events. Conclusions: Tofacitinib and biologics are efficacious and safe for UC. Further high‐quality research is warranted to establish the best therapeutic option. [ABSTRACT FROM AUTHOR]