Discontinuation of Methotrexate in Psoriasis

Abstract

Methotrexate (MTX) is the most commonly used systemic therapy for psoriasis. The drug is a folie acid antagonist and the main effect on psoriasis is thought to be inhibition of lymphatic cell proliferation (1). Due to its anti-inflammatory effect, MTX may also have a protective effect against cardiovascular disease (2,3). MTX is generally well tolerated, but common, minor adverse reactions are nausea, loss of appetite, and fatigue. Major toxicities include myelosuppression, hepatotoxicity, and pulmonary flbrosis (4).Although MTX has been used in the treatment of inflammatory disorders since the 1950s (5), there have been few evidence-based studies on MTX in the treatment of psoriasis. Results from three recent randomized controlled studies of patients with psoriasis showed that MTX was as effective as cyclosporin (6), or less effective than ciclosporin (7), and less effective than adalimumab, but more effective than placebo (8). In these studies Psoriasis Activity and Severity Index (PASI)-75 (75% improvement in PASI) for the patients treated with MTX was 60% at week 16 (6), 24% at week 12 (7), and 35.5% at week 16 (8), and rates of discontinuation of MTX therapy due to adverse reactions were 28% (6), 0% (7), and 5.5% (8), respectively.The main purpose of this study was to determine the reasons for discontinuation of MTX treatment in patients with psoriasis. Secondly, we wanted to discuss the potentially preventable or adjustable factors that might influence the specific reasons for discontinuation. METHODSWe reviewed the records of all patients who were registered as having an International Classification of Disease (ICD-10) code of psoriasis in the years 1997-2007 at our Dermatological Department. The inclusion criteria were: diagnosis of psoriasis made by a dermatologist, minimum age of 18 years, treatment with MTX at any period between 1997 and 2007, and discontinued MTX treatment before the date of data collection. We excluded patients treated with MTX because of palmoplantar pustulosis, nail psoriasis, psoriasis arthritis, or as a supplement to infliximab treatment. The main reasons for discontinuation of MTX therapy were recorded together with patient-and treatment-related data.The data were evaluated using descriptive statistics. RESULTSIn the period 1997-2007, a total of 2,221 patients with psoriasis were treated at our department. The inclusion criteria were met by 156 of these patients. Median duration of MTX therapy was 7.5 months (range 0.3-264 months), median accumulated MTX dose was 524 mg (range 15-16,925 mg), and at the end ofthe treatment median weekly MTX dose was 12.5 mg (range 2.5-30 mg). MTX was administered orally to 142 patients (91%) and 94 patients (60.3%) received folate supplementation. The most frequent main reason for discontinuation of MTX therapy was adverse reactions, which were reported in 89 patients (57%). Remission was the second most frequently reported main reason for discontinuation of MTX, followed by "lack of clinical response" and finally "non-drug-related reasons" (Tabl...

Determinants for drug survival of methotrexate in patients with psoriasis, split according to different reasons for discontinuation: results of the prospective MTX-CAPTURE

“…2 In our study, the vast majority of patients received folic acid. The study by Due et al, 14 also reported side-effects as the main reason for MTX discontinuation. In their study, only 60Á3% of the patients received folic acid supplementation.…”

Treatment Satisfaction of Patients with Psoriasis

“…According to a EUROPSO membership survey, high satisfaction was documented more frequently for methotrexate (30%) than for cyclosporine (28%) and fumaric acid (26%) (15). Methotrexate may have PASI 75 response rates of up to 60% (5), but bears a significant risk of adverse events which are the most common reason for treatment discontinuation (36).…”

Drug survival rates and reasons for drug discontinuation in psoriasis

“…Long‐term use of biologics is associated with a lower rate of adverse events than long‐term use of traditional systemic antipsoriatic drugs . While there have only been few studies comparing the reasons for discontinuation of different traditional therapies , reasons for terminating individual traditional agents have been examined in several publications, all of which identified adverse events as the most common cause . In our cohort, all treatment courses with CyA were stopped, most commonly due to adverse events.…”

“…For these patients, it would be highly desirable to achieve long‐term disease control by continued administration of a single systemic drug. However, discontinuation or switching of systemic medications because of primary or secondary treatment failure or adverse events is common . Treatment duration with traditional systemic agents such as CyA or MTX may also be limited by cumulative renal or hepatic toxicity .…”