Drug survival of methotrexate in psoriasis

Kirby, Brian

doi:10.1111/bjd.15693

Cited by 5 publications

(8 citation statements)

References 9 publications

(11 reference statements)

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“…Drug survival estimates for methotrexate, for example, also vary considerably—likely indicating variable long-term tolerability. Data from a prospective Dutch registry of patients treated with methotrexate (MTX-CAPTURE) showed drug survival rates of 63%, 30% and 15% after 1, 3 and 5 years, respectively; the median drug survival was 1.8 years [ 166 , 171 ]. Other studies showed the duration of the first treatment course to be, on average, 18.8 months [ 135 ] and that 68% of patients discontinued methotrexate after an average of ~ 4.2 months [ 172 ].…”

Section: Resultsmentioning

confidence: 99%

Long-term Safety of Oral Systemic Therapies for Psoriasis: A Comprehensive Review of the Literature

Balak

Gerdes

Parodi

et al. 2020

Dermatol Ther (Heidelb)

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Oral systemic therapies are important treatment options for patients with moderate-to-severe psoriasis, either as monotherapy or in therapy-recalcitrant cases as combination therapy with phototherapy, other oral systemics or biologics. Long-term treatment is needed to maintain sufficient disease control in psoriasis, but continuous use of systemic treatments is limited by adverse events (AEs) and cumulative toxicity risks. The primary aim of this comprehensive literature review was to examine the long-term safety profiles of oral agents commonly used in the treatment of adults with psoriasis. Searches were conducted in EMBASE and PubMed up to November 2018, and 157 relevant publications were included. Long-term treatment with acitretin could be associated with skeletal toxicity and hepatotoxicity, although evidence for skeletal toxicity is mixed and hepatotoxicity is rare, particularly at low doses. Other safety issues include hyperlipidaemia and potential for teratogenicity up to 2–3 years after discontinuation of treatment. There is a paucity of data on long-term treatment with apremilast. Continued exposure to apremilast does not seem to increase the incidence of common AEs, such as gastrointestinal (GI) AEs, upper respiratory tract infections and headache, while the long-term risks for depression, suicidal thoughts and weight loss are unknown. Long-term ciclosporin treatment is associated with renal toxicity, hypertension, non-melanoma skin cancer, neurological AEs and GI AEs. Long-term methotrexate treatment is associated with hepatotoxicity, GI AEs, haematological toxicity, renal toxicity and alopecia. Finally, long-term treatment with fumaric acid esters (FAE) is associated with GI AEs, flushing, lymphocytopenia, proteinuria and elevated liver enzymes. Median drug survival estimates varied considerably: ~ 2.9–9.7 months for apremilast; ~ 5.4 months for ciclosporin; ~ 8.6 months for acitretin; ~ 12.1–21.6 months for methotrexate; and ~ 54.8 months for FAE. These long-term safety profiles may help to guide clinicians to select the optimal oral systemic treatment for the long-term treatment of psoriasis in adults. Electronic supplementary material The online version of this article (10.1007/s13555-020-00409-4) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Long-term Safety of Oral Systemic Therapies for Psoriasis: A Comprehensive Review of the Literature

Balak

Gerdes

Parodi

et al. 2020

Dermatol Ther (Heidelb)

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“…[ 1 ] MTX as a traditional drug is recommended as induction and long-term treatment for moderate-to-severe PV and PsA. [ 2 3 ] MTX causes an inhibition of the inflammatory response by activating adenosine receptors, such as the A2A receptor. [ 4 ] Furthermore, MTX is believed to decrease the nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κΒ) activity and interleukin (IL)-17 expression.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Methotrexate in Psoriasis Vulgaris Long-Term Treatment: A Real-World Observation Study

Wilsmann-Theis,

Funk,

Mössner

et al. 2023

Indian Journal of Dermatology

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Background: Methotrexate (MTX) in the therapy of psoriasis vulgaris (PV) is a well and long-established treatment option. Aims: To assess the long-term experience of individual patients in the real world with regard to the efficacy and safety of MTX in PV therapy. Patients and Methods: In a retrospective study, MTX as a weekly used monotherapy in PV was examined. Clinical data including the Psoriasis Area Severity Index (PASI), prevalence of psoriatic-arthritis (PsA), Investigator Global Assessment (IGA), laboratory parameters, occurrence of adverse events (AEs), dosing of MTX and characteristics of patients treated for at least 24 months were collected. Results: A total of 55 patients with 247 patient-years under MTX therapy were included. The mean PASI reduction was 51.2% with a significant (P < 0.001) improvement in the skin condition in the first 6 months of treatment, remaining stable thereafter. The mean MTX dose increased from 11.8 ± 3.7 mg to 12.9 ± 3.8 mg in the first year of therapy, with a constant mean dose in the following years. In 247 patient-years, no serious AE was documented. Gastrointestinal side effects or fatigue were commonly detected. The liver parameter alanine aminotransferase/ glutamate-pyruvate transaminase (ALT/GPT) (baseline 35.8 ± 22.0 U/L) increased after 3 years of therapy (42.0 ± 22.4 U/L; P = 0.013) without clinical significance. Conclusion: In this patient collective, MTX in low doses was effective and safe in long-term therapy. The improved skin condition was steady and reached by an unvarying dose. New data showed a better efficacy of MTX in higher doses; however, additional data must be collected on the long-term efficacy and safety of MTX with a higher dose regime.

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“…Methotrexate (4-Amino-10-methylfolic acid hydrate, MTX) is an antagonist of folic acid (pteroyl-L-glutamic acid, FA) that is commonly prescribed in the treatment of various neoplastic disorders (1)(2)(3)(4), ectopic pregnancies, dermatologic conditions, voluntary early foetal terminations (5)(6)(7) and several inflammatory diseases such as psoriasis, psoriatic arthritis, inflammatory bowel disease and rheumatoid arthritis (8) systemic lupus erythematosus and juvenile arthritis (9). The use of MTX can be associated with side effects affecting various organs including stomach, intestine, haematologic system, liver, lung and central nervous system (10)(11)(12)(13)(14) which is experienced by almost one-third of the patients (15).…”

Section: Introductionmentioning

confidence: 99%

Rescuing effect of folates on methotrexate cytotoxicity in human trophoblast cells

Ravaei

Rubini

2021

Clinical and Experimental Rheumatology

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ObjectiveMethotrexate (MTX)is a folate antagonist that is administered in several conditions such as rheumatoid arthritis. Its use may associate with adverse effects presumably originating from folate deficiency. Although MTX side effects could be decreased by folate supplementation, the current guideline on folate administration is not precisely established, which could result in irreversible damage especially in high-risk groups like women in childbearing-age.Thus, this study aimed to investigate the in vitro rescuing effect of different folates including folic acid (FA), 5-methyltetrahydrofolate (MTHF) and folinic acid (5-Formyltetrahydrofolic acid, FTHF) on MTX-treated trophoblast cells. Methods HTR-8/SVneo cells were stressed with a minimum effective dose of MTX and simultaneously treated with different concentrations of FA, MTHF or FTHF. The rescuing effect was assessed by MTT viability assay. The evaluation was completed by microscopic monitoring, apoptosis assessment and measuring LINE-1 DNA methylation. ResultsThe MTT viability assay showed no MTX-rescuing effect of FA, but a significant effect of FTHF or MTHF. Microscopic observations supported the results of the viability assay. Accordingly, apoptosis was reduced in MTHF or FTHF treatments, while FA has no effect on the apoptosis induced by MTX. The LINE-1 methylation was not affected by MTX treatment, and not significantly modified in folate supplemented cultures. ConclusionsDespite the general acceptance of administering FA to prevent adverse events of MTX therapy, our findings suggest that FA may not be optimal, and indicate FTHF or MTHF as a better choice. This study on trophoblast cells suggests that FTHF may be the optimal folate, particularly for women in childbearing-age.

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Drug survival of methotrexate in psoriasis

Abstract: Linked Article: Otero et al. Br J Dermatol 2017; 177:497–504.

Cited by 5 publications

References 9 publications

Long-term Safety of Oral Systemic Therapies for Psoriasis: A Comprehensive Review of the Literature

Long-term Safety of Oral Systemic Therapies for Psoriasis: A Comprehensive Review of the Literature

Efficacy and Safety of Methotrexate in Psoriasis Vulgaris Long-Term Treatment: A Real-World Observation Study

Rescuing effect of folates on methotrexate cytotoxicity in human trophoblast cells

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