Liver Dis. 2015 Jan 22. pii: S1590-8658(15)00171-1.
Efficacy of tumour necrosis factor antagonists on remission, colectomy and hospitalisations in ulcerative colitis: Meta-analysis of placebo-controlled trials.
Lopez A, Ford AC, Colombel JF, et al.
BACKGROUND: The potential for disease modification of tumour necrosis factor antagonists in ulcerative colitis remains debated. METHODS: We searched MEDLINE, the Cochrane Library and EMBASE. Clinical response/remission, mucosal healing, colectomy, disease-related hospitalisations, and adverse events were analysed by the methods of Peto and Der Simonian and Laird.
RESULTS: Five trials enrolled 3654 patients (anti-tumour necrosis factor=2338). Anti-tumour necrosis factor therapy was more effective than placebo to induce and maintain clinical remission, with a number needed to treat of 12 (95% confidence interval [CI], 7-35) and 6 (95% CI, 4-12) for adalimumab and infliximab, respectively. Anti-tumour necrosis factor therapy was more effective than placebo to induce and maintain mucosal healing, with number needed to treat of 9 (95% CI, 5-48), 7 (95% CI, 5-17), 4 (95% CI, 3-6) for adalimumab, golimumab and infliximab, respectively. Only infliximab was associated with a reduced need for colectomy. Both infliximab and adalimumab were associated with less hospitalisations. Anti-tumour necrosis factor therapy did not increase the risk of adverse events.
CONCLUSIONS: Anti-tumour necrosis factor therapy is more effective than placebo to induce and maintain clinical remission and mucosal healing. Both infliximab and adalimumab are associated with less hospitalisations. Infliximab reduces the need for colectomy. Anti-tumour necrosis factor therapy does not increase the risk of adverse events.
Scand J Gastroenterol. 2015 Jan 30:1-8. [Epub ahead of print]
Use of a third anti-TNF after failure of two previous anti-TNFs in patients with inflammatory bowel disease: is it worth it?
Gisbert JP, Chaparro M.
Background. Some patients with inflammatory bowel disease (IBD) never respond or lose their response to a second anti-TNF. Aim. To review the efficacy and safety of a third anti-TNF after failure of two previous anti-TNFs. Methods. Bibliographical searches in PubMed for studies evaluating infliximab, adalimumab, or certolizumab as the third anti-TNF in IBD patients whose two previous anti-TNF treatments had failed. Results. Two retrospective studies with a small sample size and limited follow up evaluated the effectiveness of a third anti-TNF patients whose two previous anti-TNFs had failed. The arguments for this switching strategy are as follows: a)favorable-albeit limited-efficacy (in the study by Allez et al., clinical response was observed in 51% of patients at week 20; and in the study by de Silva et al., over 50% of patients remained on the third anti-TNF at 1 year); b)the eventual response to the third anti-TNF is relatively quick; c) no other medical options have been approved for IBD treatment; d)the only alternative options are surgery, compassionate use with non-anti-TNFs, and clinical trials. However, there are also arguments against the prescription of a third anti-TNF: a)lack of experience, since the few available studies are limited by their small sample size; b)the relatively low response in the long term (mainly due to loss of response); c) and finally, and most importantly, the risk of severe adverse events. Conclusion. The delicate balance between pros and cons means the use of a third anti-TNF after failure of two previous agents should be considered only in patients with no other therapeutic options. Decisions should be taken on an individual basis.
Aliment Pharmacol Ther. 2015 Feb 4.
Systematic review with meta-analysis: the efficacy of a second anti-TNF in patients with inflammatory bowel disease whose previous anti-TNF treatment has failed.
Gisbert JP, Marín AC, McNicholl AG, et al.
BACKGROUND: One-third of patients with Crohn's disease (CD) or ulcerative colitis (UC) receiving anti-TNFs do not respond to treatment, and a relevant proportion experience loss of response or intolerance.
AIM: To investigate the efficacy and safety of a second anti-TNF agent after primary/secondary failure or intolerance to a first drug.
METHODS: Inclusion criteria: studies evaluating the efficacy of infliximab (IFX), adalimumab (ADA) and certolizumab-pegol (CZP) as the second anti-TNF in CD or UC. Search strategy: Bibliographical searches (PubMed/Embase). Data synthesis: percentage of response/remission; the meta-analysis was performed using the inverse variance method.
RESULTS: We included 46 studies (37 CD, 8 UC, 1 pouchitis). The CD studies comprised 32 switching IFX→ADA, 4 IFX→CZP and 1 ADA→IFX. Overall, the second anti-TNF after the failure of IFX in CD induced remission in 43% and response in 63% of patients. The remission rate was higher when the reason to withdraw the first anti-TNF was intolerance (61%) than after secondary (45%) or primary failure (30%); response rates were, respectively, 72%, 62% and 53%. All UC studies switched IFX→ADA, six of them reporting remission rates ranging from 0% to 50%. Adverse events rate ranged from 0% to 81% in CD, most of them mild (serious adverse event 0-21%, discontinuation rate <20%).
CONCLUSIONS: The efficacy of a second anti-TNF in CD patients largely depends on the cause for switching. The remission rate is higher when the reason to withdraw the first anti-TNF is intolerance (61%), compared with secondary (45%) or primary failure (30%). Further studies of switch ADA→IFX are needed to evaluate this strategy.
J Crohns Colitis. 2015 Feb 5. pii: jjv031. [Epub ahead of print]
Methotrexate for maintaining remission in pediatric Crohn's patients with prior failure or intolerance to thiopurines: a multicenter cohort study.
Haisma SM, Lijftogt T, Kindermann A, et al.
BACKGROUND AND AIMS: Methotrexate (MTX) is an immunomodulating drug that can be used to maintain remission in patients with Crohn's disease (CD), but data on efficacy and tolerability in children and teenagers are scarce. We evaluated the long-term efficacy and tolerability of MTX monotherapy after thiopurine therapy in pediatric CD patients.
METHODS: A multicentre cohort of pediatric MTX users who stopped thiopurines due to ineffectiveness or intolerance between 2002 and 2012 were included and followed for at least 12 months. Relapse-free use was defined as steroid and biologic-free clinical remission after the introduction of MTX, and included intentional discontinuation of successful therapy before the end of the observation period.
RESULTS: One hundred thirteen patients with CD in remission were followed while on MTX monotherapy, of which 75 (66%) had failed on thiopurines and 38 (34%) had stopped thiopurines due to side effects. Median age at the introduction of MTX was 14 years (range 7 to 17), and 93% used the subcutaneous route. Kaplan-Meier analysis showed that 52% of the study cohort was still in steroid and biologic-free remission after 12 months of MTX monotherapy, with a difference that did not reach significance between thiopurine intolerant and thiopurine failing patients (P=0.21, log-rank test).
CONCLUSIONS: The findings of this cohort study suggest that MTX is an effective immunomodulator to maintain remission after stopping thiopurines. MTX maintenance should be considered before stepping up to anti-TNF-alpha therapy. It is probably somewhat more effective in patients who stopped thiopurines due to side effects than in those who failed on thiopurines.
United European Gastroenterol J. 2015 Feb;3(1):5-10.
The clinical value of faecal calprotectin and lactoferrin measurement in postoperative Crohn's disease.
Most patients with Crohn's disease (CD) ultimately require one or more operations over their lifetime. Nevertheless, surgery is not a cure and postoperative CD recurrence is common. Ileocolonoscopy has been considered to be the gold standard in the diagnosis and monitoring of postoperative recurrence in patients with CD. However, endoscopy is a time-consuming and invasive procedure. Simple and non-invasive methods for the detection of postoperative recurrence are desirable. Faecal inflammatory biomarkers such as calprotectin and lactoferrin provide an accurate and non-invasive diagnostic and monitoring modality for inflammatory bowel disease. However, there have been limited data on the role of faecal biomarkers in the postoperative setting. Recently, several studies evaluated the value of faecal calprotectin and lactoferrin measurement after surgery for CD. This review was conducted to assess the role of faecal calprotectin and lactoferrin measurements in patients with postoperative CD.