Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial

Reinisch, Walter; Sandborn, William J.; Hommes, Daniël W.; D’Haens, Geert R.; Hanauer, Stephen B.; Schreiber, Stefan; Panaccione, Remo; Fedorak, Richard N.; Tighe, Mary Beth; Huang, Bidan; Kampman, Wendy; Lazar, Andreas; Thakkar, Roopal

doi:10.1136/gut.2010.221127

Cited by 789 publications

(606 citation statements)

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“…The comparison between our results and those of RCTs [22,23] deserves some important consideration. In the ULTRA 1 and ULTRA 2 trials, the percentages of patients achieving remission at 8 weeks were 18.5% and 16.5% respectively.…”

Section: Discussionmentioning

confidence: 76%

“…Open-label and retrospective studies have shown that ADA can be an effective therapeutic option for inducing and maintaining remission in patients with active UC refractory or who are intolerant to standard therapy [16][17][18][19][20][21]. Recently, two randomised controlled trials (RCTs) have shown that ADA is more effective than placebo for inducing and maintaining remission in patients with moderate-to-severe UC who did not have an adequate response to conventional therapy, including steroids and immunosuppressants [22,23]. However, the absolute benefit is not impressive and this has been a matter of some debate.…”

Section: Introductionmentioning

confidence: 99%

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Adalimumab in active ulcerative colitis: A “real-life” observational study

Armuzzi¹,

Biancone²,

Daperno³

et al. 2013

Digestive and Liver Disease

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a b s t r a c tBackground and aims: The effectiveness of adalimumab in the treatment of ulcerative colitis is under debate. Although controlled trials have shown that adalimumab is significantly better than placebo, the absolute clinical benefit is modest. We report data on the effectiveness of adalimumab in a cohort of ulcerative colitis patients treated in 22 Italian centres. Methods: All patients with active disease treated with adalimumab were retrospectively reviewed. Coprimary endpoints were clinical remission at weeks 4, 12, 24 and 54. Secondary endpoints were sustained clinical remission, steroid discontinuation, endoscopic remission and need for colectomy. Results: Eighty-eight patients were included. Most patients had received previous infliximab treatment. Clinical remission rates were 17%, 28.4%, 36.4% and 43.2% at 4, 12, 24 and 54 weeks respectively. Twentytwo patients required colectomy. Clinical remission and low C-reactive protein at week 12 predicted clinical remission at week 54 (OR 4.17, 95% CI 2.36-19.44; OR 2.63, 95% CI 2.32-14.94, respectively). Previous immunosuppressant use was associated with a lower probability of clinical remission at week 54 (OR 0.67, and with a higher rate of colectomy (HR 9.7, 95% CI 1.46-9.07). Conclusion: In this large "real-life" experience adalimumab appears effective in patients with otherwise medically refractory ulcerative colitis. Patients achieving early remission can expect a better long-term outcome.

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Section: Discussionmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Adalimumab in active ulcerative colitis: A “real-life” observational study

Armuzzi¹,

Biancone²,

Daperno³

et al. 2013

Digestive and Liver Disease

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“…(adalimumab) [24], ULTRA2 (adalimumab) [25], ACT1 (infliximab) [26], ACT2 (infliximab) [26], PURSUIT-SC (golimumab) [27], PURSUIT-M (golimumab) [28] and Suzuki 2014 (adalimumab) [29]. The size of the network for each outcome varied depending on the availability of the data in each study.…”

Section: Clinical Effectiveness Evidence Submitted By the Companymentioning

confidence: 99%

“…[26], PURSUIT-SC [27], Suzuki 2014 [29] and ULTRA1 [24] included only patients who were anti-TNFnaïve. Within PURSUIT-M [28], all recruited patients were golimumab induction-responders [27].…”

Section: Critique Of Clinical Effectiveness Evidence and Interpretationmentioning

confidence: 99%

Vedolizumab for the Treatment of Adults with Moderate-to-Severe Active Ulcerative Colitis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

et al. 2015

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As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of vedolizumab (Takeda UK) to submit evidence of the clinical effectiveness and cost-effectiveness of vedolizumab for the treatment of patients with moderate-to-severe active ulcerative colitis (UC). The Evidence Review Group (ERG) produced a critical review of the evidence for the clinical effectiveness and cost-effectiveness of the technology, based upon the company's submission to NICE. The evidence was derived mainly from the GEMINI1 trial, which is a Phase III, multicentre, randomised, doubleblind, placebo-controlled trial designed to evaluate the efficacy and safety of vedolizumab as an induction and maintenance treatment in patients with moderate-to-severe active UC who had an inadequate response to, loss of response to, or intolerance to conventional therapy or anti-Tumour necrosis factor-alpha (TNF-). The clinical evidence showed that vedolizumab performed significantly better than placebo in both the induction and maintenance phases. In the post-hoc subgroup analyses, patients with or without prior anti-TNF-therapy, vedolizumab performed better then placebo (p-value not reported). In addition, a greater improvement in health-related quality of life was observed in patients treated with vedolizumab and the frequency and types of adverse events were similar between the vedolizumab and placebo group but the evidence was limited to shortterm follow-up. There were a number of limitations and uncertainties in the clinical evidence base which warrant caution in its interpretation. In particular, the post-hoc subgroup analyses and high dropout rates in the maintenance phase of the GEMINI1 trial. The company also presented a network meta-analysis of vedolizumab versus other biologics therapies indicated for moderate-to-severe UC. However, the ERG considered that the results presented may have underestimated the uncertainty in treatment effects since fixed effects models were Key Points for Decision Makers Vedolizumab appears to be more effective in both the induction and maintenance phase compared with placebo in patients with moderate-to-severe active ulcerative colitis who have had an inadequate response to, loss of response to, or intolerance to conventional therapy or TNF-inhibitor. However, the subgroup analyses for patients with or without prior TNF-inhibitor therapy were post-hoc and the study was not powered for these assessments.  The findings of the network meta-analysis of vedolizumab versus TNF-inhibitor are limited due to a number of uncertainties in treatment effects. In addition, there is currently no head-to-head randomised 3 controlled trial comparing vedolizumab to other biologic therapies indicated for moderate-to-severe ulcerative colitis.  The National Institute for Health and Care Excellence (NICE) Appraisal Committee recommended vedolizumab within its licence indication but only if the company provides vedolizumab with the discount agr...

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“…It was also the first human antibody approved for use in inflammatory bowel disease. Clinical trials showed that adalimumab is effective for treating Crohn's disease and ulcerative colitis [44][45][46][47][48][49][50][51]. Similarly to infliximab, additional pharmacokinetic studies showed that antibodies to adalimumab predicted Crohn's disease recurrence [52].…”

Section: Currently Available Therapeutic Antibodies In Digestive Disementioning

confidence: 99%

The Impact of Therapeutic Antibodies on the Management of Digestive Diseases: History, Current Practice, and Future Directions

Sofia

Rubin

2017

Dig Dis Sci

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The development of therapeutic antibodies represents a revolutionary change in medical therapy for digestive diseases. Beginning with the initial studies that confirmed the pathogenicity of cytokines in inflammatory bowel disease, the development and application of therapeutic antibodies brought challenges and insights into their potential and optimal use. Infliximab was the first biological drug approved for use in Crohn's disease and ulcerative colitis. The lessons learned from infliximab include the importance of immunogenicity and the influence of pharmacokinetics on disease response and outcomes. Building on this foundation, other therapeutic antibodies achieved approval for inflammatory bowel disease and many more are in development for several digestive diseases. In this review, we reflect on the history of therapeutic antibodies and discuss current practice and future directions for the field.

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Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial

Cited by 789 publications

References 23 publications

Adalimumab in active ulcerative colitis: A “real-life” observational study

Adalimumab in active ulcerative colitis: A “real-life” observational study

Vedolizumab for the Treatment of Adults with Moderate-to-Severe Active Ulcerative Colitis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

The Impact of Therapeutic Antibodies on the Management of Digestive Diseases: History, Current Practice, and Future Directions

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