Systematic review with meta‐analysis: endoscopic and histologic placebo rates in induction and maintenance trials of ulcerative colitis

Ma, Christopher; Guizzetti, Leonardo; Panaccione, Remo; Fedorak, Richard N.; Pai, Rish K.; Parker, Claire E; Nguyen, Tran M; Khanna, Reena; Casteele, Niels Vande; D’Haens, Geert R.; Sandborn, William J.; Feagan, Brian G.; Jairath, Vipul

doi:10.1111/apt.14672

Cited by 34 publications

(18 citation statements)

References 90 publications

(131 reference statements)

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“…However, while psoriasis represents a sensitive disease model to detect potential differences in clinical efficacy and immunogenicity between adalimumab biosimilars and the RP, ongoing pivotal studies more frequently include patients with RA, perhaps reflecting both patient population size and the potential commercial impact of RA [30]. In ulcerative colitis (UC), high and variable placebo response rates [31,32] may also present a challenge for selection of this indication for biosimilar trials. The endpoints used in biosimilar clinical trials should be appropriate and sensitive enough to detect potential differences between the RP and the proposed biosimilar [19,20].…”

Section: Key Pointsmentioning

confidence: 99%

The Future of Biosimilars: Maximizing Benefits Across Immune-Mediated Inflammatory Diseases

Kim

Alten

Avedano³

et al. 2020

Drugs

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Biologics have transformed the treatment of immune-mediated inflammatory diseases such as rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). Biosimilars-biologic medicines with no clinically meaningful differences in safety or efficacy from licensed originators-can stimulate market competition and have the potential to expand patient access to biologics within the parameters of treatment recommendations. However, maximizing the benefits of biosimilars requires cooperation between multiple stakeholders. Regulators and developers should collaborate to ensure biosimilars reach patients rapidly without compromising stringent quality, safety, or efficacy standards. Pharmacoeconomic evaluations and payer policies should be updated following biosimilar market entry, minimizing the risk of imposing nonmedical barriers to biologic treatment. In RA, disparities between treatment guidelines and national reimbursement criteria could be addressed to ensure more uniform patient access to biologics and enable rheumatologists to effectively implement treat-to-target strategies. In IBD, the cost-effectiveness of biologic treatment earlier in the disease course is likely to improve when biosimilars are incorporated into pharmacoeconomic analyses. Patient understanding of biosimilars is crucial for treatment success and avoiding nocebo effects. Full understanding of biosimilars by physicians and carefully considered communication strategies can help support patients initiating or switching to biosimilars. Developers must operate efficiently to be sustainable, without undermining product quality, the reliability of the supply chain, or pharmacovigilance. Developers should also facilitate information sharing to meet the needs of other stakeholders. Such collaboration will help to ensure a sustainable future for both the biosimilar market and healthcare systems, supporting the availability of effective treatments for patients.

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Section: Key Pointsmentioning

confidence: 99%

The Future of Biosimilars: Maximizing Benefits Across Immune-Mediated Inflammatory Diseases

Kim

Alten

Avedano³

et al. 2020

Drugs

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“…6,17,18 Central reading has been shown to be associated with significantly lower endoscopic placebo remission rates in UC patients (16% versus 25%; odds ratio, 0.52; 95% confidence interval [CI], 0.29-0.92; P ¼ .025). 19 Another meta-analysis confirmed these results, with a significant difference in mucosal healing rates among placebo-treated patients between RCTs using central reading compared with those without central reading (15% versus 30%; P ¼ .001). 6 Thus, central endoscopic reading significantly reduces the placebo effect in UC patients without reducing the treatment effect in the active group, thereby increasing active treatment effects.…”

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confidence: 84%

“…6 Thus, central endoscopic reading significantly reduces the placebo effect in UC patients without reducing the treatment effect in the active group, thereby increasing active treatment effects. 6,17,19 The positive impact of central reading on reducing placebo rates was less clear in CD trials. In a post hoc analysis of the EXTEND trial, site-based evaluation was even associated with lower remission rates in the placebo group compared with central reading and, thus, greater adalimumab-related treatment effects.…”

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confidence: 99%

Will the Placebo Effect Disappear With New Targets For Treatment of Inflammatory Bowel Diseases?

Chateau

Berre

Peyrin–Biroulet

2020

Clinical Gastroenterology and Hepatology

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“…Complete search terms are reported in Data S1. The search terms were designed by an author with expertise in library sciences (CEP) and have been used in previous systematic reviews . Additionally, abstracts from Digestive Disease Week and United European Gastroenterology Week (2012‐2017), references from relevant studies, review articles, and meta‐analyses were also searched.…”

Section: Methodsmentioning

confidence: 99%

“…The search terms were designed by an author with expertise in library sciences (CEP) and have been used in previous systematic reviews. [13][14][15][16] Additionally, abstracts from…”

Section: Introductionmentioning

confidence: 99%

Systematic review with meta‐analysis: high prevalence and cost of continued aminosalicylate use in patients with ulcerative colitis escalated to immunosuppressive and biological therapies

Guizzetti

Cipriano

et al. 2018

Aliment Pharmacol Ther

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Summary Background Aminosalicylates are the most frequently prescribed treatment for ulcerative colitis (UC). In the absence of empirical evidence, clinicians are uncertain whether to continue aminosalicylates in patients with UC after escalating therapy. Aims To quantify concomitant aminosalicylate use in UC randomised clinical trials (RCTs), identify factors associated with their use, and estimate treatment costs of concomitant aminosalicylate therapy. Methods MEDLINE, Embase, and CENTRAL were searched from inception to 1 March 2017 for placebo‐controlled RCTs of immunosuppressants, biologics, or oral small molecules in adults with UC. The proportion of patients prescribed concomitant aminosalicylates at trial entry was pooled using a random‐effects model. Meta‐regression was performed to assess trial‐level factors associated with aminosalicylate use. Treatment costs were estimated using 2018 formulary data from five Canadian provinces. Results Thirty‐two trials were included (23 induction only, nine induction, and maintenance trials). The pooled proportion of patients co‐prescribed aminosalicylates was 80.7% (95% CI 75.5%‐85.1%), with considerable observed heterogeneity (I2 = 95%). In univariable meta‐regression, aminosalicylate use was not associated with trial design, setting, year of publication, disease severity, disease duration, or drug class. The estimated direct annual treatment cost of concomitant aminosalicylates is ~$20 million for the Canadian UC population, assuming conservative estimates of UC prevalence, aminosalicylate use and dose, and the lowest cost formulation. Conclusions Approximately 80% of UC patients entering clinical trials of immunosuppressants, biologics, or oral small molecules continue to use aminosalicylates. An RCT is needed to inform the benefits and harms of continuing vs stopping aminosalicylates in patients escalating therapy.

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Systematic review with meta‐analysis: endoscopic and histologic placebo rates in induction and maintenance trials of ulcerative colitis

Abstract: Placebo endoscopic and histologic rates range from 14% to 35% in UC RCTs but are highly heterogeneous. Outcome standardisation may reduce heterogeneity and is needed in this field.

Cited by 34 publications

References 90 publications

The Future of Biosimilars: Maximizing Benefits Across Immune-Mediated Inflammatory Diseases

The Future of Biosimilars: Maximizing Benefits Across Immune-Mediated Inflammatory Diseases

Will the Placebo Effect Disappear With New Targets For Treatment of Inflammatory Bowel Diseases?

Systematic review with meta‐analysis: high prevalence and cost of continued aminosalicylate use in patients with ulcerative colitis escalated to immunosuppressive and biological therapies

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