Successive Treatment With Cyclosporine and Infliximab in Steroid-Refractory Ulcerative Colitis

Leblanc, Sarah; Allez, Matthieu; Seksik, Philippe; Flourié, Bernard; Peeters, Harald; Dupas, Jean‐Louis; Bouguen, Guillaume; Peyrin–Biroulet, Laurent; Duclos, Bernard; Bourreille, Arnaud; Dewit, Olivier; Bouhnik, Yoram; Michetti, Pierre; Chaussade, Stanislas; Saussure, Philippe de; Mary, J Y; Colombel, J F; Lémann, Marc

doi:10.1038/ajg.2011.62

Cited by 94 publications

(56 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The efficacy of calcineurin inhibitor and infliximab as salvage therapy was 75 (6/8) and 50% (4/8), respectively (p = 0.30). Several studies have reported on the efficacy and safety of infliximab as a rescue therapy for UC refractory to calcineurin inhibitor [9,10,11,12]. In each study, infliximab was deemed a successful rescue therapeutic option in patients with UC refractory to calcineurin inhibitor.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Salvage Therapy and Its Effect on Operative Outcomes in Patients with Ulcerative Colitis

Saito

Nagahori²,

Fujii³

et al. 2014

Digestion

View full text Add to dashboard Cite

Aims: To evaluate the efficacy and safety of salvage therapy, and to identify risk factors of operative complications among hospitalized ulcerative colitis (UC) patients. Patients and Methods: We evaluated 88 UC patients hospitalized at our center between April 2010 and November 2012. We compared characteristics of corticosteroid-refractory patients treated with calcineurin inhibitor and those with infliximab as second-line therapy. Furthermore, we compared the characteristics of operative and nonoperative patients. The association between perioperative treatments and complications was also investigated. Results: Calcineurin inhibitor and infliximab were used in 42 and 22 patients, respectively. We found no difference in the clinical background between them. Efficacy rates were 67 and 50%, respectively. Eight out of 10 nonresponders of each treatment were treated with the other drug as third-line therapy. The efficacy rates of calcineurin inhibitor and infliximab as the third-line therapy were 75 and 50%, respectively. Operative patients had more severe disease (87.5 vs. 31%, p < 0.01), higher Lichtiger score (14.1 vs. 11.5, p < 0.01), higher Rachmilewitz endoscopic index (10.5 vs. 8.4, p < 0.01), higher C-reactive protein (7.6 vs. 4.0, p = 0.015) and lower serum albumin (3.1 vs. 3.6, p = 0.014) than nonoperative patients. Complications were observed in 7 out of 16 (44 %) operative patients. Postoperative complications were not increased even when patients were treated with second- or third-line therapy. However, the complication rate in corticosteroid users was 54.5 (6/11) and 20% (1/5) in nonusers. Conclusions: Third-line salvage therapy is effective and tolerable in carefully selected UC patients. Perioperative use of corticosteroids may lead to more adverse outcomes.

show abstract

Section: Discussionmentioning

confidence: 99%

Efficacy of Salvage Therapy and Its Effect on Operative Outcomes in Patients with Ulcerative Colitis

Saito

Nagahori²,

Fujii³

et al. 2014

Digestion

View full text Add to dashboard Cite

show abstract

“…But we don't have that freedom (Scotland governed by SMC) (245, 250) HP13 I'm not a massive NICE supporter but I actually think their guidance has been pretty sensible (346) HP13 they as a national body have to have their eye on healthcare costs and I think to favour the cheaper drug if in a situation where there is such a big difference between the 2 drugs is sensible, but also to acknowledge that it's not absolutely the right drug for everybody (429) HP14 I think the current NICE guidelines are um, a bit tricky because I think if you are going to give a patient infliximab you need to give them ., and then they respond to it, if they do respond to it you want to be able to continue the treatment and I think it may have more of a long term use than the NICE guidelines that we're currently using (38) HP14 I think it's unduly restrictive and I think it will eventually change. I think it's actually quite hard to adhere to actually as well.…”

Section: Excellentmentioning

confidence: 99%

“…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

Successive Treatment With Cyclosporine and Infliximab in Steroid-Refractory Ulcerative Colitis

Abstract: In patients with intravenous steroid-refractory UC and who fail to respond to CYS or IFX, a second-line rescue therapy may be effective in carefully selected patients, avoiding colectomy within 2 months in two-thirds of them. The risk/benefit ratio should still be considered individually.

Cited by 94 publications

References 27 publications

Efficacy of Salvage Therapy and Its Effect on Operative Outcomes in Patients with Ulcerative Colitis

Efficacy of Salvage Therapy and Its Effect on Operative Outcomes in Patients with Ulcerative Colitis

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