Discontinuation of infliximab in patients with ulcerative colitis in remission (HAYABUSA): a multicentre, open-label, randomised controlled trial

Taku, Keisei; Motoya, Satoshi; Nakamura, Shirô; Yamamoto, Takayuki; Nagahori, Masakazu; Tanaka, Shinji; Hisamatsu, Tadakazu; Hirai, Fumihito; Nakase, Hiroshi; Watanabe, Kenji; Matsumoto, Takayuki; Tanaka, Masanori; Abe, Takayuki; Suzuki, Yasuo; Watanabe, Mamoru; Hibi, Toshifumi; Kato, Shingo; Maemoto, Atsushi; Matsuura, Minoru; Sakemi, Ryosuke; Sasaki, Makoto; Tsujikawa, Tomoyuki; Esaki, Motohiro; Fukata, Norimasa; Kitamura, Kazuya; Hiraoka, Sakiko; Hokari, Ryota; Ishihara, Shunji; Mizoshita, Tsutomu; Naito, Yuji; Saruta, Masayuki; Yoshino, Takayuki

doi:10.1016/s2468-1253(21)00062-5

Cited by 39 publications

(34 citation statements)

References 30 publications

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“…Regarding IBD, 1 year after anti-TNF-α discontinuation 42% of CD patients and 28% of UC patients experience a disease flare [ 155 ]. In line with the aforementioned data, only 54% from UC patients who discontinued infliximab were in remission one year after drug withdrawal [ 156 ]. In another study, 0%–54% of IBD patients who tapered anti-TNF-α dose experienced a disease flare [ 157 ].…”

Section: Introductionmentioning

confidence: 66%

The second decade of anti-TNF-a therapy in clinical practice: new lessons and future directions in the COVID-19 era

et al. 2022

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Since the late 1990s, tumor necrosis factor alpha (TNF-α) inhibitors (anti-TNFs) have revolutionized the therapy of immune-mediated inflammatory diseases (IMIDs) affecting the gut, joints, skin and eyes. Although the therapeutic armamentarium in IMIDs is being constantly expanded, anti-TNFs remain the cornerstone of their treatment. During the second decade of their application in clinical practice, a large body of additional knowledge has accumulated regarding various aspects of anti-TNF-α therapy, whereas new indications have been added. Recent experimental studies have shown that anti-TNFs exert their beneficial effects not only by restoring aberrant TNF-mediated immune mechanisms, but also by de-activating pathogenic fibroblast-like mesenchymal cells. Real-world data on millions of patients further confirmed the remarkable efficacy of anti-TNFs. It is now clear that anti-TNFs alter the physical course of inflammatory arthritis and inflammatory bowel disease, leading to inhibition of local and systemic bone loss and to a decline in the number of surgeries for disease-related complications, while anti-TNFs improve morbidity and mortality, acting beneficially also on cardiovascular comorbidities. On the other hand, no new safety signals emerged, whereas anti-TNF-α safety in pregnancy and amid the COVID-19 pandemic was confirmed. The use of biosimilars was associated with cost reductions making anti-TNFs more widely available. Moreover, the current implementation of the “treat-to-target” approach and treatment de-escalation strategies of IMIDs were based on anti-TNFs. An intensive search to discover biomarkers to optimize response to anti-TNF-α treatment is currently ongoing. Finally, selective targeting of TNF-α receptors, new forms of anti-TNFs and combinations with other agents, are being tested in clinical trials and will probably expand the spectrum of TNF-α inhibition as a therapeutic strategy for IMIDs.

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Section: Introductionmentioning

confidence: 66%

The second decade of anti-TNF-a therapy in clinical practice: new lessons and future directions in the COVID-19 era

et al. 2022

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Section: Zusammenfassungmentioning

confidence: 99%

“…Several cohort studies and only one open-label randomized controlled trial analyzed exit strategies of TNFα antibody therapy in UC patients [69,74]. At week 48 after infliximab cessation, the UC relapse rate was 19.6 % for continued therapy vs. 45.7 % for therapy withdrawal [74]. Overall, combined endoscopic and clinical remission predicted a higher probability of sustained remission after TNFα antibody cessation.…”

Section: Zusammenfassungmentioning

confidence: 99%

Questions to consider when caring for patients with ulcerative colitis

et al. 2022

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Although the management of patients with ulcerative colitis (UC) is well defined by national and international guidelines, there are many debates and open questions related to daily care of UC patients. Here, we aimed to review topics with high clinical relevance including therapy algorithms, potential biomarkers for disease prognosis and response to therapy, the role of interventions targeting the gut microbiota, insights from head-to-head trials, novel UC medications, exit strategies, the impact of COVID19 on UC, care of patients with acute severe disease, cancer screening, and the role of surgery.

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“…However, due to the cost of these therapies and the preference of many patients to withdraw therapy if feasible, one should explore the potential of biomarkers to predict disease recurrence upon treatment discontinuation in patients in deep remission. Randomized (unblinded) trials have demonstrated that a subset of patients does indeed not experience relapse after anti-TNF withdrawal ( Kobayashi et al., 2021 ). A post-hoc analysis of the STORI trial identified a potential proteomic signature predictive of disease recurrence ( Pierre et al., 2020 ), though validation in the SPARE trial (NCT02177071) and other large datasets is required prior to implementation in daily clinical practice ( Verstockt et al., 2021b ; Louis, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Biomarker discovery for personalized therapy selection in inflammatory bowel diseases: Challenges and promises

Alsoud

Vermeire

Verstockt

2022

Current Research in Pharmacology and Drug Discovery

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The past decades witnessed a significant stride in deciphering the pathophysiology of inflammatory bowel disease, which further advanced drug development adding several new biologicals and small molecules to the arsenal of available therapies. Surprisingly, this wealth in therapeutic options did not yield the aspired high durable response rates. In addition, the increase in therapeutic availabilities ignited an increase in research toward biomarkers that could help assign therapies to patients with the highest probability of response. Luckily, major steps have been undertaken in this domain which resulted in the discovery of some interesting biomarkers that are still under validation. However, the pace in which this domain is progressing, the discordance between short-term endpoints in biomarker discovery studies and the ambition of the disease community in modifying disease course, and the uncertainties about the validity of discovered biomarkers highlight the need for a critical appraisal of research conduct in this domain. In this review, we shed light on areas of improvement in biomarker discovery studies that will help optimize the use of available therapies and break the current therapeutic ceiling.

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Discontinuation of infliximab in patients with ulcerative colitis in remission (HAYABUSA): a multicentre, open-label, randomised controlled trial

Cited by 39 publications

References 30 publications

The second decade of anti-TNF-a therapy in clinical practice: new lessons and future directions in the COVID-19 era

The second decade of anti-TNF-a therapy in clinical practice: new lessons and future directions in the COVID-19 era

Questions to consider when caring for patients with ulcerative colitis

Biomarker discovery for personalized therapy selection in inflammatory bowel diseases: Challenges and promises

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