Tumour necrosis factor inhibitor monotherapy vs combination with MTX in the treatment of PsA: a systematic review of the literature

Behrens, Frank; Cañete, Juan D.; Olivieri, Ignazio; Kuijk, Arno W R van; McHugh, Neil; Combe, Bernard

doi:10.1093/rheumatology/keu415

Cited by 72 publications

(52 citation statements)

References 43 publications

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“…A randomized trial found that MTX monotherapy did not improve joint counts or other measures of articular disease activity in patients with PsA compared with placebo 5 , suggesting that MTX alone may have minimal clinical effects in this patient population. However, the influence of MTX in combination with TNF inhibitors has not been well studied in PsA 4 . A study based on observational data from Norway did not detect a difference in clinical responses with the concomitant use of MTX and TNF inhibitors, but the authors stressed that they did not have the data to address the issue of peripheral versus axial disease, a major potential confounding factor 8 .…”

Section: Discussionmentioning

confidence: 99%

Does Concomitant Methotrexate with Adalimumab Influence Treatment Outcomes in Patients with Psoriatic Arthritis? Data from a Large Observational Study

Behrens

Koehm²,

Arndt³

et al. 2015

J Rheumatol

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Objective.To examine the influence of concomitant methotrexate (MTX) with adalimumab (ADA) on outcomes in patients with psoriatic arthritis (PsA) using data from an observational study of ADA.Methods.Data from a German noninterventional study of patients with PsA starting treatment with ADA were analyzed retrospectively for effects of concomitant MTX on key outcomes, including Disease Activity Score-28 joints, tender and swollen joint counts, skin assessments, and safety. Patients were categorized into those with symptoms of axial involvement and those with no symptoms of axial involvement as judged by the examining clinician.Results.A total of 1455 patients met the study criteria, 296 with axial involvement (ADA monotherapy = 165; plus MTX = 131) and 1159 with no axial involvement (ADA monotherapy = 658; plus MTX = 501). ADA, alone or combined with MTX, resulted in strong and comparable reductions in disease activity measures in patients with and those without axial disease over 24 months of therapy. In multiple regression analyses, concomitant MTX did not affect joint or skin outcomes in either the group with axial manifestations or the group without axial disease. Neither adverse event rates nor withdrawal rates were significantly influenced by concomitant MTX.Conclusion.ADA is an effective treatment option for patients with PsA with or without axial involvement. Compared with ADA monotherapy, the use of concomitant MTX with ADA does not improve articular or skin outcomes in patients with PsA regardless of axial symptoms. Trial registration: Clinicaltrials.govNCT01111240

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Section: Discussionmentioning

confidence: 99%

Does Concomitant Methotrexate with Adalimumab Influence Treatment Outcomes in Patients with Psoriatic Arthritis? Data from a Large Observational Study

Behrens

Koehm²,

Arndt³

et al. 2015

J Rheumatol

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“…Inhibition of TNF results in the downregulation of abnormal and progressive inflammatory processes, resulting in target organ damage. 4,5,10,11,19,27 It has been experimentally proven that TNF inhibitors prohibit organ tissue damage by suppressing the formation of TNF-α, proinflammatory cytokines, and nitric oxide. 5,26,27 A decrease in edema, acinar cell edema, and necrotic cells was observed in Group 3 (p < 0.05) ( Table 2) after the administration of ADA.…”

Section: A B Cmentioning

confidence: 99%

“…3,4 Methotrexate is used to treat many different types of cancer (colorectal, breast, and pancreatic cancers) and inflammatory diseases (rheumatoid arthritis − RA, psoriatic arthritis, systemic lupus erythematosus, and dermatomyositis). [1][2][3][4][5] Nevertheless, its use is associated with side effects such as fibrosis affecting the liver, lung, and other organs. 1,2,5 Acute intense MTX side effects are dose-dependent.…”

Section: Introductionmentioning

confidence: 99%

“…It has been proposed in recent studies that MTX has a cytotoxic effect in reducing intracellular tetrahydrofolate, but the mechanism of MTX-induced toxicity is not well known. 1,2,[4][5][6][7][8][9][10][11] Methotrexate has been used in the treatment of pancreatic cancer, but there has been no research into its side effects on the pancreas, an organ which is relatively sensitive to various toxic substances and drugs. High-dose substances, causing oxidative stress, have been reported to have a toxic effect on the pancreas.…”

Section: Introductionmentioning

confidence: 99%

“…The tolerance mechanism of the metabolites in MTX is not known. 1,2,4,5,11 Physicians increase the dosage of MTX to counter the development of tolerance. Accordingly, the risk of MTX toxicity increases.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Protective effects of tumor necrosis factor alpha inhibitors on methotrexate-induced pancreatic toxicity

Mercantepe¹,

Kalkan²,

Tümkaya³

et al. 2018

Adv Clin Exp Med

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Background. Methotrexate (MTX), a folate antagonist, is commonly used in the treatment of many different types of cancer and inflammatory diseases, including pancreatic cancer, although its side effects on the pancreas have not yet been researched. The mechanism of MTX-induced toxicity is not well known, and it has been reported in high-dose toxicity studies that the pancreas is sensitive to toxic effects.

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Efficacy and Safety of Bimekizumab in Patients With Psoriatic Arthritis With or Without Methotrexate: 52‐Week Results From Two Phase 3 Studies

McInnes,

Mease,

Tanaka

et al. 2024

ACR Open Rheumatology

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ObjectiveThe objective of this study was to assess 52‐week efficacy and safety of bimekizumab in patients with active psoriatic arthritis (PsA) with or without concomitant methotrexate (+/−MTX) treatment at baseline.MethodsWe conducted a post hoc analysis of patients in BE OPTIMAL (NCT03895203; biologic disease‐modifying antirheumatic drug [bDMARD]‐naïve), BE COMPLETE (NCT03896581; prior inadequate response or intolerance to tumor necrosis factor inhibitors [TNFi‐IR]), and the BE VITAL open‐label extension (NCT04009499) study. Patients were randomized to one of the following treatment groups: bimekizumab 160 mg every four weeks, placebo, or a reference drug (adalimumab 40 mg every two weeks; BE OPTIMAL only). From Week 16, placebo‐randomized patients received bimekizumab. Missing data were imputed using non‐responder imputation, multiple imputation, or worst‐category imputation.ResultsThrough Week 52, similar proportions of bimekizumab‐treated patients achieved American College of Rheumatology 50% (ACR50) response criteria for both +MTX and −MTX (BE OPTIMAL: 54.4% +MTX, 54.7% −MTX; BE COMPLETE: 56.3% +MTX, 48.0% −MTX). Similar proportions of bimekizumab‐treated patients achieved complete skin clearance (Psoriasis Area and Severity Index 100% [PASI100] response) and minimal disease activity in both +MTX and −MTX groups. Similar trends were seen in placebo/bimekizumab‐treated patients. Through Week 52, the proportion of bimekizumab‐treated patients with ≥1 treatment‐emergent adverse event were similar between the +MTX and −MTX groups (BE OPTIMAL 325 of 410 [79.3%] vs 230 of 292 [78.8%], BE COMPLETE 105 of 168 [62.5%] vs 138 of 220 [62.7%]). The safety profile was comparable between subgroups and consistent with the prior safety profile of bimekizumab.ConclusionTreatment with bimekizumab demonstrated consistent, sustained efficacy to 52 weeks in bDMARD‐naïve and TNFi‐IR patients with PsA and was well tolerated, irrespective of concomitant MTX.

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Tumour necrosis factor inhibitor monotherapy vs combination with MTX in the treatment of PsA: a systematic review of the literature

Cited by 72 publications

References 43 publications

Does Concomitant Methotrexate with Adalimumab Influence Treatment Outcomes in Patients with Psoriatic Arthritis? Data from a Large Observational Study

Does Concomitant Methotrexate with Adalimumab Influence Treatment Outcomes in Patients with Psoriatic Arthritis? Data from a Large Observational Study

Protective effects of tumor necrosis factor alpha inhibitors on methotrexate-induced pancreatic toxicity

Efficacy and Safety of Bimekizumab in Patients With Psoriatic Arthritis With or Without Methotrexate: 52‐Week Results From Two Phase 3 Studies

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