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The METOP trial published in The Lancet shows lasting efficacy and safety of subcutaneous methotrexate over one year in plaque-type psoriasis patients

The METOP trial published in The Lancet shows lasting efficacy and safety of subcutaneous methotrexate over one year in plaque-type psoriasis patients

  • The results of the phase 3 METOP trial demonstrate that self-administered subcutaneous methotrexate has a rapid onset of action and is significantly better than placebo in improving the skin condition and quality of life of plaque-type psoriasis, with efficacy and safety sustained over one year.
  • Subcutaneous methotrexate in an intensified dosing schedule showed a favourable 52 week risk-benefit profile in patients with psoriasis. Consideration should be given to the route of administration and intensified dosing schedule when using methotrexate in this patient group.

Wedel, Germany (08 March 2017). Medac announced today that the 1-year results of the METOP trial on subcutaneous methotrexate had been published in The Lancet[1]. Methotrexate has been used in plaque-type psoriasis as an effective systemic treatment for more than 50 years and is considered a first-line therapy according to current treatment guidelines[2],[3]. But so far there have not been any high-quality clinical trials with subcutaneous methotrexate in long-term therapy.

Now, however, new data published in The Lancet show “a favourable 52 week risk-benefit profile of subcutaneous methotrexate in patients with psoriasis. The route of administration and the intensified dosing schedule should be considered when methotrexate is used in this patient group”[1].

The Methotrexate Optimized treatment schedule in patients with Psoriasis (METOP) trial is a randomised, double-blind, placebo-controlled phase 3 trial, evaluating the efficacy and safety of self-administered subcutaneous methotrexate in patients with moderate to severe plaque-type psoriasis using an optimised dosing regimen[4]. The trial enrolled a total of 120 adult patients with plaque-type psoriasis from 13 centres in Germany, France, the Netherlands and the United Kingdom. As one of the conditions for entry to the trial, patients had to have been diagnosed at least 6 months beforehand. Individuals that previously underwent a MTX-therapy, as well as those with highly active psoriatic arthritis, hepatic impairment or a low leucocyte count were excluded from the trial.

Trial participants received a weekly methotrexate starting dose of 17.5 mg subcutaneously using a pre-filled syringe. If, by week 8, patients had not achieved at least a 50% improvement in the Psoriasis Area and Severity Index (PASI) score, the dose was increased to 22.5 mg/week. The placebo group switched to methotrexate after week 16. The treatment was continued up until week 52 in the whole patient population.

As the study in The Lancet reports, 41% in the methotrexate group and 10% in the placebo group achieved a PASI 75 in week 16. The response rates continued to increase up until week 52, by which time 45% in the methotrexate group had a PASI 75 and almost a third of subjects met the criteria for a PASI 90[1].

Quality of life had improved after just 16 weeks in 59% of methotrexate-treated patients and at this point 43% no longer had any impairment. In the placebo group, the figures were only 34% and 10%, respectively.

No serious adverse reactions were observed. As expected, gastrointestinal complaints and elevations of liver enzymes occurred more often on methotrexate compared with placebo. A small proportion of subjects was suffering from fatigue.

In a substudy the molecular mechanism of action of subcutaneous methotrexate in psoriasis was investigated. Skin samples were taken at the start of the trial and after 16 weeks of treatment. The biopsies of the PASI 75 responders were found to have reduced mRNA expression of pro-inflammatory cytokines: compared with baseline, IL-17 mRNA expression fell to 10% and that of interferon γ to 25%. A clinical response was, moreover, associated with a significant reduction in important inflammatory cells such as the CD11c+ dendritic cells and CD3+ T cells. Values close to those in healthy skin were achieved.

The results of the METOP trial show that subcutaneous injection of methotrexate 50 mg/ml using a starting dose of 17.5 mg/week greatly reduces the severity of plaque-type psoriasis and improves quality of life while at the same time being well tolerated. Furthermore, the demonstrated correlation between the reduction in specific cytokines and inflammatory cells suggests an inhibitory effect of methotrexate on the TH1/TH17 pathway in the skin.

The study results published in The Lancet support the subcutaneous administration of methotrexate for the treatment of psoriasis. They also underline the current European[2] and US[5] guidelines recommending methotrexate as a cost-effective[6] systemic first-line treatment in psoriasis.

 

  1. Warren, RB et al., An intensified dosing schedule of subcutaneous methotrexate in patients with moderate to severe plaque-type psoriasis (METOP): a 52 week, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;389:528-537
  2. Nast A et al., European S3-Guidelines on the systemic treatment of psoriasis vulgaris – Update 2015 – Short version – EDF in cooperation with EADV and IPC. J Eur Acad Dermatol Venereol 2015;29:2277-2294
  3. Warren, RB et al., British Association of Dermatologists’ guidelines for the safe and effective prescribing of methotrexate for skin disease 2016. Br J Dermatol. 2016;175:23-44
  4. ClinicalTrials.gov: Trial in Patients With Psoriasis Treated With Methotrexate Using an Optimized Treatment Schedule (METOP). https://clinicaltrials.gov/ct2/show/NCT02902861 (06.03.2017)
  5. Menter A et al., Guidelines of care for the management of psoriasis and psoriatic arthritis: section 6. Guidelines of care for the treatment of psoriasis and psoriatic arthritis: case-based presentations and evidence-based conclusions. J Am Acad Dermatol 2011; 65:137-174
  6. D’Souza LS et al., Estimated cost efficacy of systemic treatments that are approved by the US Food and Drug Administration for the treatment of moderate to severe psoriasis. J Am Acad Dermatol 2015;72:589-598

 

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medac Gesellschaft für klinische Spezialpräparate mbH
medac is a privately held German pharmaceutical company located in Wedel, Tornesch and Hamburg. Medicinal products from medac support doctors and patients throughout the world in overcoming their acute and persistent diseases in the indication areas of oncology & haematology, urology and autoimmune disorders. In addition, medac develops and markets special diagnostic test systems. Since 1970, medac has been committed to unifying therapeutic and diagnostic agents under one roof.

You can find further information on the company and its products on the internet under www.medac.de.