دورية أكاديمية
Comparing methotrexate monotherapy with methotrexate plus leflunomide combination therapy in psoriatic arthritis (COMPLETE-PsA): a double-blind, placebo-controlled, randomised, trial.
| العنوان: | Comparing methotrexate monotherapy with methotrexate plus leflunomide combination therapy in psoriatic arthritis (COMPLETE-PsA): a double-blind, placebo-controlled, randomised, trial. |
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| المؤلفون: | Mulder MLM; Department of Rheumatology, Sint Maartenskliniek, Nijmegen, Netherlands; Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, Netherlands. Electronic address: m.mulder@maartenskliniek.nl., Vriezekolk JE; Department of Research, Sint Maartenskliniek, Nijmegen, Netherlands., van Hal TW; Department of Rheumatology, Sint Maartenskliniek, Nijmegen, Netherlands; Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, Netherlands., Nieboer LM; Department of Rheumatology, Sint Maartenskliniek, Nijmegen, Netherlands., den Broeder N; Department of Rheumatology, Sint Maartenskliniek, Nijmegen, Netherlands., de Jong EMGJ; Department of Dermatology, Radboud University Medical Center, Nijmegen, Netherlands., den Broeder AA; Department of Rheumatology, Sint Maartenskliniek, Nijmegen, Netherlands., van den Hoogen FHJ; Department of Rheumatology, Sint Maartenskliniek, Nijmegen, Netherlands., Helliwell PS; Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK., Wenink MH; Department of Rheumatology, Sint Maartenskliniek, Nijmegen, Netherlands. |
| المصدر: | The Lancet. Rheumatology [Lancet Rheumatol] 2022 Apr; Vol. 4 (4), pp. e252-e261. Date of Electronic Publication: 2022 Feb 28. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Ltd Country of Publication: England NLM ID: 101765308 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2665-9913 (Electronic) Linking ISSN: 26659913 NLM ISO Abbreviation: Lancet Rheumatol Subsets: PubMed not MEDLINE; MEDLINE |
| أسماء مطبوعة: | Original Publication: [London] : Elsevier Ltd., [2019]- |
| مستخلص: | Background: Conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs) are the preferred first-line treatment in patients with psoriatic arthritis, although there is a paucity of evidence for the efficacy of conventional synthetic DMARDs and especially their combination. We aimed to investigate whether a combination of methotrexate plus leflunomide is superior to methotrexate monotherapy at improving disease activity in patients with psoriatic arthritis. Methods: This single centre, investigator-initiated, double-blind, randomised, placebo-controlled trial was conducted at Sint Maartenskliniek in the Netherlands (locations included Boxmeer, Geldrop, Woerden, and Nijmegen). Patients aged 16 years or older with a clinical diagnosis of psoriatic arthritis and active disease (defined as two or more swollen joints; dactylitis counting as one swollen joint) were included. Patients were randomly allocated (1:1) and stratified by high disease activity (psoriatic arthritis disease activity score [PASDAS] ≥5·4) to either methotrexate plus leflunomide (combination therapy) or methotrexate plus placebo (monotherapy), using computer-generated stratified variable block randomisation. In both groups, patients received oral methotrexate 15 mg per week for the first 4 weeks and 25 mg per week thereafter combined with two leflunomide 10 mg tablets once per day or two placebo tablets. During the study period, the patients, nurses, researchers, and treating physicians were all masked to treatment allocation. The primary outcome was the difference in mean PASDAS at week 16, adjusted for baseline PASDAS, between the combination and monotherapy groups, assessed in the intention-to-treat population. This trial was registered with the Netherlands Trial Register (NL7404) on Dec 3, 2018. Findings: Between Feb 19, 2019, and March 11, 2021, 82 patients were screened for eligibility. Four patients were ineligible and 78 were enrolled and randomly assigned to either methotrexate plus leflunomide (n=39) or methotrexate plus placebo (n=39). 50 (64%) of 78 patients were male, 28 (36%) were female, and the median age of patients was 55·0 years (IQR 42·0-64·0). Methotrexate plus leflunomide combination therapy was superior to methotrexate monotherapy at week 16 (PASDAS 3·1 [SD 1·4] vs 3·7 [SD 1·3]; treatment difference -0·6, 90% CI -1·0 to -0·1; p=0·025). There were no study deaths. The most frequently occurring adverse events were nausea or vomiting (17 [44%] of 39 patients in the methotrexate plus leflunomide group vs 11 [28%] of 39 in the methotrexate plus placebo group), tiredness (9 [23%] vs 13 [33%]) and elevated alanine aminotransferase (12 [31%] vs 7 [18%]. Generally, the incidence of mostly mild adverse events was higher in the methotrexate plus leflunomide group than in the methotrexate plus placebo group. Interpretation: Methotrexate plus leflunomide combination therapy results in greater improvement in disease activity according to PASDAS in patients with psoriatic arthritis. However, methotrexate plus leflunomide combination therapy is less well tolerated than methotrexate monotherapy. Funding: Regional Junior Researcher Grant from the Sint Maartenskliniek. Competing Interests: Declaration of interests JEV reports payment and honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Eli Lilly and personal funding from Galapagos Biopharma. EMGJdJ received research grants from AbbVie, Novartis, Janssen Pharmaceutica, Leo Pharma, and UCB for research on psoriasis; acted as consultant, paid speaker, and participated in research sponsored by companies that manufacture drugs used for the treatment of psoriasis or eczema including AbbVie, Almirall, Janssen Pharmaceutica, Novartis, Lily, Celgene, Leo Pharma, Sanofi, UCB, and Galapagos Biopharma (funding is not personal but goes to the independent research fund of the Department of Dermatology in Radboud University Medical Centre). PSH reports payment and honoraria for lectures, presentations, speaker bureaus, manuscript writing or educational events from Pfizer and Abbvie (payments made to the institution), Novartis, and Janssen (personal funding and payments made to the institution); and received consulting fees from Eli Lilly. TWvH reports speaker fees from Eli Lilly and Novartis; and support for attending meetings from UCB. All other authors declare no competing interests. (Copyright © 2022 Elsevier Ltd. All rights reserved.) |
| تواريخ الأحداث: | Date Created: 20240130 Latest Revision: 20240130 |
| رمز التحديث: | 20240130 |
| DOI: | 10.1016/S2665-9913(22)00028-5 |
| PMID: | 38288921 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2665-9913 |
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| DOI: | 10.1016/S2665-9913(22)00028-5 |