Long Term Use of Leflunomide as a Cause of Severe Diarrhea?

Günendi, Zafer; Benli, Esin; Göğüş, Feride; Atalay, Fatma

doi:10.5152/akd.2010.08

Cited by 4 publications

(3 citation statements)

References 12 publications

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“…As such, the current mainstay for diagnosis appears to also be its treatment: symptomatic improvement after medication cessation. [1][2][3] This case demonstrates an example of leflunomide-induced colitis which should be considered in patients who present with symptoms of abdominal pain and diarrhea in the setting of leflunomide use, even months to years after medication initiation.…”

Section: Answer To: Image 3 (Page 2034): Drug-induced Colitis Secondamentioning

confidence: 98%

Colitis in a Rheumatologic Patient

2020

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Section: Answer To: Image 3 (Page 2034): Drug-induced Colitis Secondamentioning

confidence: 98%

Colitis in a Rheumatologic Patient

2020

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“…These adverse effects may complicate their long-term use in other immune-related conditions. For instance, while leflunomide has shown efficacy in CD, its adverse effect of diarrhea is not acceptable in an IBD patient population [22]. In the COMPONENT study, neither diarrhea nor alopecia were observed at a higher rate as a consequence of therapy with vidofludimus compared with placebo.…”

Section: Off-target Effects: Diarrhea Alopecia and Neutropeniamentioning

confidence: 99%

“…While leflunomide is widely used in treating RA, either as a monotherapy or in combination with methotrexate [18], the class of DHODH inhibitors to which both leflunomide and teriflunomide belong have been the subject of numerous safety concerns since their approval by the FDA. Postmarket surveillance includes reports of a variety of drug-related adverse reactions, including elevated liver enzymes and hepatotoxicity, peripheral neuropathy, vasculitis, hypertension, alopecia, pruritus, nausea, and diarrhea [16,[19][20][21][22][23][24][25][26][27][28]. In one prospective study evaluating leflunomide treatment in 136 RA patients, 65% of patients experienced at least that inhibitors of DHODH show immunomodulatory activity, which is most pronounced on T cells [3][4][5][6][7][8], with T helper (Th) 1 and Th17 cells acting as important contributors to the inflammatory processes of RA [9].…”

Section: Key Pointsmentioning

confidence: 99%

The Selective Oral Immunomodulator Vidofludimus in Patients with Active Rheumatoid Arthritis: Safety Results from the COMPONENT Study

Muehler¹,

Kohlhof²,

Groeppel³

et al. 2019

Drugs R D

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Introduction The dihydroorotate dehydrogenase (DHODH) inhibitors leflunomide and teriflunomide are immunomodulatory agents approved to treat rheumatoid arthritis (RA) and multiple sclerosis, respectively, and are actively being investigated as therapeutic agents for other immune-related diseases; however, both structurally related compounds have a number of potentially serious adverse effects. Vidofludimus, a new selective second-generation DHODH inhibitor, is chemically distinct from leflunomide/teriflunomide and appears to exhibit a distinct safety profile. Objective The aim of the COMPONENT study was to assess the efficacy, safety, and pharmacokinetics of vidofludimus in the treatment of patients with active RA on a background therapy of methotrexate. This report focuses solely on the safety results of the COMPONENT trial. Methods Patients received once-daily oral vidofludimus (N = 122) or placebo (N = 119) along with their standard of care methotrexate treatment for 13 weeks. Efficacy endpoints were assessed. Safety parameters were monitored throughout treatment and at follow-up. Plasma concentrations of vidofludimus were measured. Results The primary efficacy endpoint, American College of Rheumatology 20 (ACR 20) responder rate at 13 weeks, demonstrated numerical superiority in the treatment group compared with placebo; however, it did not reach statistical significance. Nonetheless, the COMPONENT study yielded important safety and pharmacokinetic data that could provide important information regarding the use of vidofludimus in other clinical trials, not only for RA but also for other autoimmune diseases. A safety profile for vidofludimus similar to placebo was obtained in this RA patient population. This includes similar rates of the adverse events of diarrhea, alopecia, neutropenia, and elevated liver enzymes, all of which are known drug-related adverse events reported for leflunomide and teriflunomide. A potential pharmacokinetic interaction between vidofludimus and methotrexate was observed. Conclusions Vidofludimus demonstrated a positive safety profile, making it a promising candidate for the treatment of a variety of immune-related diseases. Trial Registrations ClinicalTrials.gov identifier: NCT01010581.

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Leflunomide-induced colitis in association with enterocutaneous fistula in an immunosuppressed patient with renal transplant and rheumatoid arthritis

Kwok

Morosin

2019

Clin J Gastroenterol

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Long Term Use of Leflunomide as a Cause of Severe Diarrhea?

Cited by 4 publications

References 12 publications

Colitis in a Rheumatologic Patient

Colitis in a Rheumatologic Patient

The Selective Oral Immunomodulator Vidofludimus in Patients with Active Rheumatoid Arthritis: Safety Results from the COMPONENT Study

Leflunomide-induced colitis in association with enterocutaneous fistula in an immunosuppressed patient with renal transplant and rheumatoid arthritis

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