A Randomized Trial of Methotrexate in Combination With Infliximab for the Treatment of Crohn's Disease

Feagan, Brian; McDonald, John W.D.; Panaccione, Remo; Enns, Robert; Bernstein, Çharles N.; Ponich, Terry; Bourdages, Raymond; MacIntosh, Donald; Dallaire, Chrystian; Cohen, Albert; Fedorak, Richard; Paré, Pierre; Bitton, Alain; Saibil, Fred; Anderson, Frank H.; Donner, Allan; Wong, Cindy J.; Zou, Guang Yong; Vandervoort, Margaret K.; Hopkins, Marybeth; Greenberg, Gordon R.

doi:10.1053/j.gastro.2008.05.061

Cited by 68 publications

(62 citation statements)

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“…Finally, Sokol et al [15] found that patients with AZA cotreatment had less frequent flare-ups and perianal complications compared to patients on methotrexate cotreatment. This result is in accordance with the COMMIT (Combination of Maintenance Methotrexate-Infliximab Trial) study by Feagan et al [13] who documented that concomitant treatment with methotrexate does not result in any additive effect.…”

Section: Concomitant Treatment With Biological Agentssupporting

confidence: 92%

Biological Treatment of Crohn’s Disease

Nielsen

Bjerrum²,

Seidelin³

et al. 2012

Dig Dis

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Introduction of biological agents for the treatment of Crohn’s disease (CD) has led to a transformation of the treatment paradigm. Several biological compounds have been approved for patients with CD refractory to conventional treatment: infliximab, adalimumab and certolizumab pegol (and natalizumab in several countries outside the European Union). However, despite the use of biologics for more than a decade, questions still remain about the true efficacy and the best treatment regimens – especially about when to discontinue treatment. Furthermore, a need for optimizing treatment with biologics still exists, as 20–40% of patients with CD (depending on selection criteria) do not have any relevant response to the current biological agents (i.e. primary failures). A better patient selection might maximize the clinical outcome while minimizing the complications associated with this type of therapy. However, the clinical tools capable of identifying such patients are still unavailable, and the trough level strategy may help the clinician to optimize therapy and to avoid loss of response and/or immunogenicity (i.e. a low but measurable antibody level exists just before the periodic administration of the biological agent). On the other hand, peak levels and average levels should not exceed concentrations associated with increased toxicity. Randomized, controlled studies focusing on trough levels and antibodies towards the biological agent in routine clinical situations may add important pieces to the puzzle for a more rational treatment algorithm of CD patients. In some situations, the risks (i.e. immunogenicity, serious infections and the promotion of neoplasia) may, however, not outweigh the benefits of biological treatment.

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Section: Concomitant Treatment With Biological Agentssupporting

confidence: 92%

Biological Treatment of Crohn’s Disease

Nielsen

Bjerrum²,

Seidelin³

et al. 2012

Dig Dis

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“…While pretreatment with corticosteroids prior to an infliximab infusion may reduce antibody levels, there was no significant difference in the proportion of patients who developed detectable antibodies nor did this strategy ameliorate infusion reactions [Farrell et al 2003]. [Feagan et al 2008]. Important patient differences exist, as the patients in the SONIC trial were started on combination therapy early in the course of their disease suggesting combination therapy may be more successful with early intervention and this may influence future antibody development.…”

Section: Evidence For Biologicsmentioning

confidence: 99%

Exploring the role of monitoring anti-TNFα drug and antibody levels in the management of inflammatory bowel disease

Lim

Panaccione

Seow

2010

Therap Adv Gastroenterol

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Crohn's disease and ulcerative colitis are chronic inflammatory gastrointestinal disorders which often result in significant morbidity or surgery. Current treatment options are not curative and may cause significant adverse effects. The introduction of anti-tumour necrosis factor alpha (anti-TNFa) therapy over a decade ago was a welcome addition to the therapeutic armamentarium and revolutionized the treatment of inflammatory bowel disease (IBD). Despite their relative success, a significant proportion of patients with IBD fail to respond or subsequently lose response anti-TNFa therapy. This review identifies and explores the role of drug levels and immunogenicity (antibody formation) on the efficacy of anti-TNFa therapy and details how monitoring these parameters may help to optimize the management of patients with IBD.

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“…Sixty percent of those continuing dual therapy needed to change their infliximab schedule compared to 55% of those on infliximab monotherapy (not statistically different). Finally, a recent study examined whether concomitant methotrexate and infliximab were more effective than infliximab alone in adult patients receiving corticosteroids who initiated biologic therapy [20] . At 50 weeks, 30.6% of those on dual therapy had failed compared to 29.8% of those on infliximab alone.…”

Section: Concomitant Use Of Immunomodulators and Biologic Therapymentioning

confidence: 99%

Risk/Benefit Strategies Must Be Employed in the Management of Pediatric Crohn’s Disease

Hyams

2009

Dig Dis

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Clinicians caring for children with Crohn’s disease must consider the long-term implications of therapeutic interventions and cumulative diagnostic studies in their patients whose disease duration will be measured in decades. There is evidence of the increased severity of pediatric Crohn’s disease compared to its adult counterpart, its frequent co-morbid growth disturbances, and the frequent need for aggressive medical therapies including immunomodulators and biological agents. The initial management of most children diagnosed with Crohn’s disease involves enteral nutritional support, corticosteroids, and immunomodulators. Corticosteroids, while initially helpful in decreasing signs and symptoms of disease, are occasionally ineffective, generally do not heal mucosa, impair growth, and are frequently associated with a state of corticosteroid dependency. Immunomodulators are effective maintenance therapies with corticosteroid sparing effects, but have no value in the acutely ill child. The emergence of biological therapy with its impressive record of rapid efficacy and use as maintenance therapy has prompted discussion of its incorporation into initial management, but has also raised concerns about who are the most suitable candidates, which if any medications can be used concomitantly, and long-term safety. The combined use of thiopurines and anti-TNF agents may predispose to a rare and uniformly fatal lymphoma. Identification of children at high risk for complicated disease may allow us to better evaluate risk/benefit in newly diagnosed children, and biologic agents are likely to assume an increasing role in primary therapy in those deemed at highest risk. Long-term observations will determine whether biologics will change natural history and demonstrate adequate safety.

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A Randomized Trial of Methotrexate in Combination With Infliximab for the Treatment of Crohn's Disease

Cited by 68 publications

References 0 publications

Biological Treatment of Crohn’s Disease

Biological Treatment of Crohn’s Disease

Exploring the role of monitoring anti-TNFα drug and antibody levels in the management of inflammatory bowel disease

Risk/Benefit Strategies Must Be Employed in the Management of Pediatric Crohn’s Disease

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