Systematic review: Methotrexate—A poorly understood and underused medication in inflammatory bowel disease

Summary Background Methotrexate, an immunosuppressant used for the treatment of inflammatory bowel disease (IBD) for over 30 years, remains underused compared to thiopurines. Aims To review the efficacy, safety, optimal dosing and delivery regimens of methotrexate in adults with IBD. Methods We cond...

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Published inAlimentary pharmacology & therapeutics Vol. 60; no. 6; pp. 686 - 700
Main Authors Sequier, Léa, Caron, Bénédicte, Loeuille, Damien, Honap, Sailish, Jairath, Vipul, Netter, Patrick, Danese, Silvio, Sibilia, Jean, Peyrin‐Biroulet, Laurent
Format Journal Article
LanguageEnglish
Published England Wiley Subscription Services, Inc 01.09.2024
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Online AccessGet full text
ISSN0269-2813
1365-2036
1365-2036
DOI10.1111/apt.18194

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Abstract Summary Background Methotrexate, an immunosuppressant used for the treatment of inflammatory bowel disease (IBD) for over 30 years, remains underused compared to thiopurines. Aims To review the efficacy, safety, optimal dosing and delivery regimens of methotrexate in adults with IBD. Methods We conducted a systematic review of studies involving patients with IBD treated with methotrexate from inception to August 2023. All studies were included from the MEDLINE database via PubMed. Results For Crohn's disease, we included eight randomised controlled trials (RCTs) and 17 observational studies. Parenteral methotrexate effectively increased remission rates in steroid‐dependent patients at 25 mg/week for 16 weeks and at 15 mg/week for maintenance. Methotrexate can be used in combination with anti‐tumour necrosis factor (TNF) agents to reduce immunogenicity. Data comparing thiopurines and methotrexate remain scarce. For ulcerative colitis (UC), we included five RCTs and 10 observational studies were included; there was no evidence to support the use of methotrexate in (UC). We extracted safety data from 17 studies; mild‐to‐moderate adverse effects were common. The incidence of liver fibrosis or cirrhosis was low. Conclusion Methotrexate is effective at inducing and maintaining remission in steroid‐refractory Crohn's disease and can reduce anti‐TNF‐induced immunogenicity when used in combination therapy. Data regarding tolerance and safety are reassuring. These findings challenge preconceived ideas on methotrexate and suggest that it is a valid first‐line conventional option for the treatment of mild‐to‐moderate Crohn's disease.
AbstractList Methotrexate, an immunosuppressant used for the treatment of inflammatory bowel disease (IBD) for over 30 years, remains underused compared to thiopurines. To review the efficacy, safety, optimal dosing and delivery regimens of methotrexate in adults with IBD. We conducted a systematic review of studies involving patients with IBD treated with methotrexate from inception to August 2023. All studies were included from the MEDLINE database via PubMed. For Crohn's disease, we included eight randomised controlled trials (RCTs) and 17 observational studies. Parenteral methotrexate effectively increased remission rates in steroid-dependent patients at 25 mg/week for 16 weeks and at 15 mg/week for maintenance. Methotrexate can be used in combination with anti-tumour necrosis factor (TNF) agents to reduce immunogenicity. Data comparing thiopurines and methotrexate remain scarce. For ulcerative colitis (UC), we included five RCTs and 10 observational studies were included; there was no evidence to support the use of methotrexate in (UC). We extracted safety data from 17 studies; mild-to-moderate adverse effects were common. The incidence of liver fibrosis or cirrhosis was low. Methotrexate is effective at inducing and maintaining remission in steroid-refractory Crohn's disease and can reduce anti-TNF-induced immunogenicity when used in combination therapy. Data regarding tolerance and safety are reassuring. These findings challenge preconceived ideas on methotrexate and suggest that it is a valid first-line conventional option for the treatment of mild-to-moderate Crohn's disease.
BackgroundMethotrexate, an immunosuppressant used for the treatment of inflammatory bowel disease (IBD) for over 30 years, remains underused compared to thiopurines.AimsTo review the efficacy, safety, optimal dosing and delivery regimens of methotrexate in adults with IBD.MethodsWe conducted a systematic review of studies involving patients with IBD treated with methotrexate from inception to August 2023. All studies were included from the MEDLINE database via PubMed.ResultsFor Crohn's disease, we included eight randomised controlled trials (RCTs) and 17 observational studies. Parenteral methotrexate effectively increased remission rates in steroid‐dependent patients at 25 mg/week for 16 weeks and at 15 mg/week for maintenance. Methotrexate can be used in combination with anti‐tumour necrosis factor (TNF) agents to reduce immunogenicity. Data comparing thiopurines and methotrexate remain scarce. For ulcerative colitis (UC), we included five RCTs and 10 observational studies were included; there was no evidence to support the use of methotrexate in (UC). We extracted safety data from 17 studies; mild‐to‐moderate adverse effects were common. The incidence of liver fibrosis or cirrhosis was low.ConclusionMethotrexate is effective at inducing and maintaining remission in steroid‐refractory Crohn's disease and can reduce anti‐TNF‐induced immunogenicity when used in combination therapy. Data regarding tolerance and safety are reassuring. These findings challenge preconceived ideas on methotrexate and suggest that it is a valid first‐line conventional option for the treatment of mild‐to‐moderate Crohn's disease.
Summary Background Methotrexate, an immunosuppressant used for the treatment of inflammatory bowel disease (IBD) for over 30 years, remains underused compared to thiopurines. Aims To review the efficacy, safety, optimal dosing and delivery regimens of methotrexate in adults with IBD. Methods We conducted a systematic review of studies involving patients with IBD treated with methotrexate from inception to August 2023. All studies were included from the MEDLINE database via PubMed. Results For Crohn's disease, we included eight randomised controlled trials (RCTs) and 17 observational studies. Parenteral methotrexate effectively increased remission rates in steroid‐dependent patients at 25 mg/week for 16 weeks and at 15 mg/week for maintenance. Methotrexate can be used in combination with anti‐tumour necrosis factor (TNF) agents to reduce immunogenicity. Data comparing thiopurines and methotrexate remain scarce. For ulcerative colitis (UC), we included five RCTs and 10 observational studies were included; there was no evidence to support the use of methotrexate in (UC). We extracted safety data from 17 studies; mild‐to‐moderate adverse effects were common. The incidence of liver fibrosis or cirrhosis was low. Conclusion Methotrexate is effective at inducing and maintaining remission in steroid‐refractory Crohn's disease and can reduce anti‐TNF‐induced immunogenicity when used in combination therapy. Data regarding tolerance and safety are reassuring. These findings challenge preconceived ideas on methotrexate and suggest that it is a valid first‐line conventional option for the treatment of mild‐to‐moderate Crohn's disease.
Methotrexate, an immunosuppressant used for the treatment of inflammatory bowel disease (IBD) for over 30 years, remains underused compared to thiopurines.BACKGROUNDMethotrexate, an immunosuppressant used for the treatment of inflammatory bowel disease (IBD) for over 30 years, remains underused compared to thiopurines.To review the efficacy, safety, optimal dosing and delivery regimens of methotrexate in adults with IBD.AIMSTo review the efficacy, safety, optimal dosing and delivery regimens of methotrexate in adults with IBD.We conducted a systematic review of studies involving patients with IBD treated with methotrexate from inception to August 2023. All studies were included from the MEDLINE database via PubMed.METHODSWe conducted a systematic review of studies involving patients with IBD treated with methotrexate from inception to August 2023. All studies were included from the MEDLINE database via PubMed.For Crohn's disease, we included eight randomised controlled trials (RCTs) and 17 observational studies. Parenteral methotrexate effectively increased remission rates in steroid-dependent patients at 25 mg/week for 16 weeks and at 15 mg/week for maintenance. Methotrexate can be used in combination with anti-tumour necrosis factor (TNF) agents to reduce immunogenicity. Data comparing thiopurines and methotrexate remain scarce. For ulcerative colitis (UC), we included five RCTs and 10 observational studies were included; there was no evidence to support the use of methotrexate in (UC). We extracted safety data from 17 studies; mild-to-moderate adverse effects were common. The incidence of liver fibrosis or cirrhosis was low.RESULTSFor Crohn's disease, we included eight randomised controlled trials (RCTs) and 17 observational studies. Parenteral methotrexate effectively increased remission rates in steroid-dependent patients at 25 mg/week for 16 weeks and at 15 mg/week for maintenance. Methotrexate can be used in combination with anti-tumour necrosis factor (TNF) agents to reduce immunogenicity. Data comparing thiopurines and methotrexate remain scarce. For ulcerative colitis (UC), we included five RCTs and 10 observational studies were included; there was no evidence to support the use of methotrexate in (UC). We extracted safety data from 17 studies; mild-to-moderate adverse effects were common. The incidence of liver fibrosis or cirrhosis was low.Methotrexate is effective at inducing and maintaining remission in steroid-refractory Crohn's disease and can reduce anti-TNF-induced immunogenicity when used in combination therapy. Data regarding tolerance and safety are reassuring. These findings challenge preconceived ideas on methotrexate and suggest that it is a valid first-line conventional option for the treatment of mild-to-moderate Crohn's disease.CONCLUSIONMethotrexate is effective at inducing and maintaining remission in steroid-refractory Crohn's disease and can reduce anti-TNF-induced immunogenicity when used in combination therapy. Data regarding tolerance and safety are reassuring. These findings challenge preconceived ideas on methotrexate and suggest that it is a valid first-line conventional option for the treatment of mild-to-moderate Crohn's disease.
Author Loeuille, Damien
Peyrin‐Biroulet, Laurent
Caron, Bénédicte
Danese, Silvio
Sibilia, Jean
Sequier, Léa
Jairath, Vipul
Netter, Patrick
Honap, Sailish
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CitedBy_id crossref_primary_10_1016_S2468_1253_24_00355_8
crossref_primary_10_1016_j_bpg_2025_101994
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Snippet Summary Background Methotrexate, an immunosuppressant used for the treatment of inflammatory bowel disease (IBD) for over 30 years, remains underused compared...
Methotrexate, an immunosuppressant used for the treatment of inflammatory bowel disease (IBD) for over 30 years, remains underused compared to thiopurines. To...
BackgroundMethotrexate, an immunosuppressant used for the treatment of inflammatory bowel disease (IBD) for over 30 years, remains underused compared to...
Methotrexate, an immunosuppressant used for the treatment of inflammatory bowel disease (IBD) for over 30 years, remains underused compared to...
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SubjectTerms Cirrhosis
Clinical trials
Crohn's disease
Fibrosis
Immunogenicity
Inflammatory bowel disease
Inflammatory bowel diseases
Intestine
Liver diseases
Methotrexate
Observational studies
Remission
Remission (Medicine)
Steroids
Systematic review
Tumor necrosis factor
Tumor necrosis factor-TNF
Ulcerative colitis
Title Systematic review: Methotrexate—A poorly understood and underused medication in inflammatory bowel disease
URI https://onlinelibrary.wiley.com/doi/abs/10.1111%2Fapt.18194
https://www.ncbi.nlm.nih.gov/pubmed/39076140
https://www.proquest.com/docview/3097497664
https://www.proquest.com/docview/3086064828
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