Infliximab salvage therapy after failure of ciclosporin in corticosteroid‐refractory ulcerative colitis: a multicentre study

Chaparro, María; Burgueño, P.; Iglesias, Eva; Panés, J; Muñoz, Fernándo; Bastida, Guillermo; Castro, Luísa; Jiménez, Carlos; Mendoza, Juan L.; Acosta, Manuel Barreiro‐de; Senent, Silvia Gómez; Gomollón, Fernando; Calvet, Xavier; Garcia-Planella, E.; Gómez, Mayra Virginia Ramos; Hernández, Vicent; Hinojosa, Joaquín; Mañosa, Míriam; Nyssen, Olga P.; Gisbert, Javier P.

doi:10.1111/j.1365-2036.2011.04934.x

Cited by 103 publications

(44 citation statements)

References 34 publications

(43 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Treatment with infliximab for a long period can result in the development of antibodies by the host against this molecule, reducing the duration of response to treatment, and increasing the risk of adverse events (52). A multicenter study on corticosteroid-refractory UC patients, in whom cyclosporin had failed, showed that the use of infliximab avoids colectomy in a relatively high percentage of patients, although 23% developed adverse events (38).…”

Section: Oxidative Stress and Inflammation In The Gutmentioning

confidence: 99%

Inflammatory Bowel Disease: Mechanisms, Redox Considerations, and Therapeutic Targets

Biasi

Leonarduzzi

Oteiza

et al. 2013

Antioxidants & Redox Signaling

209

127

View full text Add to dashboard Cite

Oxidative stress is thought to play a key role in the development of intestinal damage in inflammatory bowel disease (IBD), because of its primary involvement in intestinal cells' aberrant immune and inflammatory responses to dietary antigens and to the commensal bacteria. During the active disease phase, activated leukocytes generate not only a wide spectrum of pro-inflammatory cytokines, but also excess oxidative reactions, which markedly alter the redox equilibrium within the gut mucosa, and maintain inflammation by inducing redoxsensitive signaling pathways and transcription factors. Moreover, several inflammatory molecules generate further oxidation products, leading to a self-sustaining and auto-amplifying vicious circle, which eventually impairs the gut barrier. The current treatment of IBD consists of long-term conventional anti-inflammatory therapy and often leads to drug refractoriness or intolerance, limiting patients' quality of life. Immune modulators or anti-tumor necrosis factor a antibodies have recently been used, but all carry the risk of significant side effects and a poor treatment response. Recent developments in molecular medicine point to the possibility of treating the oxidative stress associated with IBD, by designing a proper supplementation of specific lipids to induce local production of anti-inflammatory derivatives, as well as by developing biological therapies that target selective molecules (i.e., nuclear factor-jB, NADPH oxidase, prohibitins, or inflammasomes) involved in redox signaling. The clinical significance of oxidative stress in IBD is now becoming clear, and may soon lead to important new therapeutic options to lessen intestinal damage in this disease.

show abstract

Section: Oxidative Stress and Inflammation In The Gutmentioning

confidence: 99%

Inflammatory Bowel Disease: Mechanisms, Redox Considerations, and Therapeutic Targets

Biasi

Leonarduzzi

Oteiza

et al. 2013

Antioxidants & Redox Signaling

209

127

View full text Add to dashboard Cite

show abstract

“…We used the electronic search strategies checklist of the Cochrane Collaboration. 31 We identified nine observational studies and one RCT [32][33][34][35][36][37][38][39][40][41] that compared the efficacy and safety of ciclosporin with those of infliximab ( Table 1). Although both ciclosporin and infliximab were effective in steroid-resistant UC, results did not agree which drug was better.…”

Section: Review Of Literaturementioning

confidence: 99%

Comparison Of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis: pragmatic randomised Trial and economic evaluation (CONSTRUCT)

Williams

Alam

Alrubaiy

et al. 2016

Health Technol Assess

View full text Add to dashboard Cite

BackgroundThe efficacy of infliximab and ciclosporin in treating severe ulcerative colitis (UC) is proven, but there has been no comparative evaluation of effectiveness.ObjectiveTo compare the clinical effectiveness and cost-effectiveness of infliximab and ciclosporin in treating steroid-resistant acute severe UC.MethodBetween May 2010 and February 2013 we recruited 270 participants from 52 hospitals in England, Scotland and Wales to an open-label parallel-group, pragmatic randomised trial. Consented patients admitted with severe colitis completed baseline quality-of-life questionnaires before receiving intravenous hydrocortisone. If they failed to respond within about 5 days, and met other inclusion criteria, we invited them to participate and used a web-based adaptive randomisation algorithm to allocate them in equal proportions between 5 mg/kg of intravenous infliximab at 0, 2 and 6 weeks or 2 mg/kg/day of intravenous ciclosporin for 7 days followed by 5.5 mg/kg/day of oral ciclosporin until 12 weeks from randomisation. Further treatment was at the discretion of physicians responsible for clinical management. The primary outcome was quality-adjusted survival (QAS): the area under the curve (AUC) of scores derived from Crohn’s and Ulcerative Colitis Questionnaires completed by participants at 3 and 6 months, and then 6-monthly over 1–3 years, more frequently after surgery. Secondary outcomes collected simultaneously included European Quality of Life-5 Dimensions (EQ-5D) scores and NHS resource use to estimate cost-effectiveness. Blinding was possible only for data analysts. We interviewed 20 trial participants and 23 participating professionals. Funded data collection finished in March 2014. Most participants consented to complete annual questionnaires and for us to analyse their routinely collected health data over 10 years.ResultsThe 135 participants in each group were well matched at baseline. In 121 participants analysed in each group, we found no significant difference between infliximab and ciclosporin in QAS [mean difference in AUC/day 0.0297 favouring ciclosporin, 95% confidence interval (CI) –0.0088 to 0.0682;p = 0.129]; EQ-5D scores (quality-adjusted life-year mean difference 0.021 favouring ciclosporin, 95% CI –0.032 to 0.096;p = 0.350); Short Form questionnaire-6 Dimensions scores (mean difference 0.0051 favouring ciclosporin, 95% CI –0.0250 to 0.0353;p = 0.737). There was no statistically significant difference in colectomy rates [odds ratio (OR) 1.350 favouring infliximab, 95% CI 0.832 to 2.188;p = 0.223]; numbers of serious adverse reactions (event ratio = 0.938 favouring ciclosporin, 95% CI 0.590 to 1.493;p = 0.788); participants with serious adverse reactions (OR 0.660 favouring ciclosporin, 95% CI 0.282 to 1.546;p = 0.338); numbers of serious adverse events (event ratio 1.075 favouring infliximab, 95% CI 0.603 to 1.917;p = 0.807); participants with serious adverse events (OR 0.999 favouring infliximab, 95% CI 0.473 to 2.114;p = 0.998); deaths (all three who died received infliximab;p = 0.247) or concomitant use of immunosuppressants. The lower cost of ciclosporin led to lower total NHS costs (mean difference –£5632, 95% CI –£8305 to –£2773;p < 0.001). Interviews highlighted the debilitating effect of UC; participants were more positive about infliximab than ciclosporin. Professionals reported advantages and disadvantages with both drugs, but nurses disliked the intravenous ciclosporin.ConclusionsTotal cost to the NHS was considerably higher for infliximab than ciclosporin. Nevertheless, there was no significant difference between the two drugs in clinical effectiveness, colectomy rates, incidence of SAEs or reactions, or mortality, when measured 1–3 years post treatment. To assess long-term outcome participants will be followed up for 10 years post randomisation, using questionnaires and routinely collected data. Further studies will be needed to evaluate the efficacy and effectiveness of new anti-tumour necrosis factor drugs and formulations of ciclosporin.Trial registrationCurrent Controlled Trials ISRCTN22663589.FundingThis project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 20, No. 44. See the NIHR Journals Library website for further project information.

show abstract

“…There have been some reports of switching from ciclosporin to infliximab and vice versa if one treatment is not effective. [24][25][26][27] However, higher rates of adverse events and mortality due to long-term stronger immunosuppression have warned that administering the sequential therapy should be carefully decided on an individual basis. If we could predict the efficiency of the individual treatment for severe refractory UC with high accuracy, an early clinical decision-making would be made and ineffective medications would be avoided before patients undergo long-term stronger immunosuppression.…”

Section: Resultsmentioning

confidence: 99%

Predictive factors of response to intravenous ciclosporin in severe ulcerative colitis: the development of a novel prediction formula

Saito

Katsuno

Nakagawa

et al. 2012

Aliment Pharmacol Ther

View full text Add to dashboard Cite

show abstract

Infliximab salvage therapy after failure of ciclosporin in corticosteroid‐refractory ulcerative colitis: a multicentre study

Abstract: SUMMARY Background

Cited by 103 publications

References 34 publications

Inflammatory Bowel Disease: Mechanisms, Redox Considerations, and Therapeutic Targets

Inflammatory Bowel Disease: Mechanisms, Redox Considerations, and Therapeutic Targets

Comparison Of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis: pragmatic randomised Trial and economic evaluation (CONSTRUCT)

Predictive factors of response to intravenous ciclosporin in severe ulcerative colitis: the development of a novel prediction formula

Contact Info

Product

Resources

About