Latest news with #methotrexate
Medscape
2 days ago
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- Medscape
Secukinumab in Early PsA Starts Fast vs Standard of Care
TOPLINE: More patients with recently diagnosed psoriatic arthritis (PsA) saw clinical improvement by 3 months in a treat-to-target strategy with secukinumab, a monoclonal antibody targeting interleukin-17, compared with those on standard-of-care treatment, but this difference was not seen at later 3-month intervals out to 1 year. METHODOLOGY: In a randomized, open-label, manufacturer-sponsored, multicenter trial, 120 patients (mean age, 49; 41% women) diagnosed with PsA within the prior 3 months were randomized to a treat-to-target approach of early treatment with secukinumab or standard of care in which treatment escalated according to predetermined steps if patients failed to respond. At the start, in the secukinumab arm, 60 patients received 300 mg monthly secukinumab, a single injection of 80 mg triamcinolone, and 15 mg/wk methotrexate plus 10 mg/wk folic acid. In the standard-of-care arm, 60 patients received 80 mg triamcinolone (single injection), methotrexate starting at 15 mg/wk and increasing to 25 mg/wk by 6 weeks, and 10 mg/wk folic acid. In the standard-of-care arm, treatment was escalated by adding sulfasalazine 1000 mg twice daily if needed, then switching if needed to a first or second TNF inhibitor with methotrexate. In the secukinumab arm, patients with poor response were escalated to a TNF inhibitor with 25 mg methotrexate per week, followed by a second TNF inhibitor plus methotrexate if needed. Outcomes were measured at 3, 6, 9, and 12 months, and the primary endpoint was the percentage of patients achieving 50% or greater improvement in American College of Rheumatology response criteria (ACR50) at 6 months. TAKEAWAY: At 6 months, both trial arms had similar ACR50 rates (around 41% in the secukinumab arm vs 37% in the standard-of-care arm). However, first-line secukinumab was associated with significantly more patients achieving ACR50 at 3 months (about 42% vs 22%; P < .05). Secondary endpoints of the percentage of patients meeting criteria for Minimal Disease Activity, 90% improvement in Psoriasis Area Severity Index, and resolution of enthesitis and dactylitis generally followed the same pattern of quicker responses in the secukinumab arm, followed by numerically greater but not statistically significant differences in the secukinumab vs standard-of-care arms at later timepoints. IN PRACTICE: 'Early response is very important to patients. They don't necessarily care whether they are eventually going to catch up. They want to know they'll feel much better at 3 months,' commented Dafna Gladman, MD, senior scientist at the Toronto Western Research Institute and professor in the Institute of Medical Science at the University of Toronto, both in Toronto, Ontario, Canada. She was not a part of the study. SOURCE: Gonul Hazal Koc, MD, of Erasmus MC in Rotterdam, the Netherlands, led the research and presented the 12-month results in a poster at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2025 Annual Meeting and Trainee Symposium in Bogotá, Colombia. LIMITATIONS: The study was not blinded, and a treat-to-target approach, while recommended by several guidelines, does not necessarily represent routine clinical practice in PsA. DISCLOSURES: Koc and her colleagues' research was supported by an unrestricted grant to her institution by Novartis, the manufacturer of secukinumab, which also supplied the study reported having no financial relationships outside the grant to her institution. Gladman has received research support and/or consultant fees from AbbVie, Amgen, Bristol-Myers Squibb, Johnson & Johnson, Eli Lilly, Fresenius Kabi, Novartis, Galapagos, UCB, Gilead, Janssen, Roche, and Pfizer.
Medscape
22-07-2025
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- Medscape
Methotrexate Success Varies in Ectopic Pregnancy Types
TOPLINE: Overall success rates for intramuscular (IM) methotrexate were comparable between recurrent and primary ectopic pregnancy cases, but single-dose treatment was less effective in recurrent cases. Analysis of 3944 patients revealed that multidose regimens achieved similar success rates in both groups, suggesting a potential benefit of routine multidose treatment for recurrent cases. METHODOLOGY: Researchers conducted systematic searches of MEDLINE, EMBASE, and Scopus databases through February 2025, following PRISMA guidelines for meta-analysis. Analysis included 3944 patients (502 with recurrent and 3442 with primary ectopic pregnancy) from 15 observational studies, with patients aged ≥ 18 years receiving IM methotrexate treatment. The primary outcome measure was treatment success, defined as complete resolution of ectopic pregnancy without requiring further intervention. TAKEAWAY: Single-dose IM methotrexate had lower success rates in patients with recurrent ectopic pregnancy than in those with a primary ectopic pregnancy (relative risk [RR], 0.79; 95% CI, 0.63-1.00; P = .050). Multidose IM methotrexate treatment showed no significant difference in success rates between recurrent and primary ectopic pregnancy groups (RR, 1.14; 95% CI, 0.71-1.84; P = .590). Substantial heterogeneity was observed among studies analyzing single-dose (I² = 73.0%) and multidose (I² = 64.0%) treatment outcomes. IN PRACTICE: 'Current observational data suggest that patients with recurrent ectopic pregnancy should be considered for multidose IM methotrexate to achieve similar rates of success compared with primary ectopic pregnancy,' wrote the authors of the study. SOURCE: The study was led by Shreya Bhat, MBChB, PGDipOMG, Department of Obstetrics and Gynaecology, Palmerston North Hospital, Te Whatu Ora MidCentral in Palmerston North, Aotearoa New Zealand. It was published online in Obstetrics & Gynecology. LIMITATIONS: According to the authors, substantial heterogeneity in outcome definitions and baseline cohort characteristics between studies affected the analysis. Most studies were retrospective cohort designs, introducing potential selection bias and confounding factors. The researchers noted that over 50% of studies failed to identify relevant confounding variables, which likely contributed to the large observed CIs for effect estimates. DISCLOSURES: The authors did not report any potential conflicts of interest. This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
Medscape
03-07-2025
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- Medscape
Methotrexate Boosts Steroid-Free Remission in Early PMR
BARCELONA, Spain — Compared with placebo, adding methotrexate (MTX) to treatment for newly diagnosed polymyalgia rheumatica (PMR) nearly doubled glucocorticoid (GC)-free remission rates at 1 year, according to research presented at European Alliance of Associations for Rheumatology (EULAR) 2025 Annual Meeting. Patients in the MTX group also achieved GC-free remission sooner than those in the placebo group, but researchers did not find that adding MTX significantly reduced the cumulative GC dose. Previous studies evaluating MTX as a GC-sparing agent in PMR have had variable results, said Aatke van der Maas, MD, PhD, a rheumatologist at Sint Maartenskliniek, Nijmegen, the Netherlands, who presented the findings at the meeting. However, these earlier trials used lower doses than those typically used for other rheumatic diseases. 'We wanted to look at whether MTX at 25 mg weekly would be effective in achieving GC-free remission in recently diagnosed PMR patients,' she said. Van der Maas previously presented results from this trial at the American College of Rheumatology 2024 Annual Meeting in Washington, DC. At that time, the analysis suggested that MTX did not increase GC-free remission rates; however, due to a coding error that resulted in some patients being placed in the wrong allocation group, those older results were considered erroneous. These updated results followed an audit and re-analysis of the source data. Targeting Early Disease The interleukin-6 receptor antagonist sarilumab is already approved for PMR in patients who have had an inadequate response to corticosteroids or could not tolerate a corticosteroid taper. But this trial targeted a different patient population, said Sara K. Tedeschi, MD, MPH, of Brigham and Women's Hospital, Boston. 'It's a very different scenario, and one that I think is very attractive about the study,' she told Medscape Medical News . Tedeschi was not involved in the research. 'For many patients with PMR, it would be great to discuss starting a steroid-sparing agent at the time of diagnosis, rather than needing to wait many months to see how they respond to a steroid taper before deciding to add a steroid-sparing agent.' To see whether a higher MTX dose resulted in higher steroid-free remission rates, researchers recruited 64 patients who had been diagnosed with PMR within the past 12 weeks. All patients met the 2012 EULAR/ACR classification criteria for PMR and had been taking GCs for < 8 weeks. Patients with other rheumatic inflammatory conditions, contraindications to MTX, or those receiving other immunomodulatory therapies were excluded. Patients were randomly assigned in a 1:1 ratio to receive a weekly dose of 25 mg oral MTX or placebo. An accelerated GC taper accompanied both treatment groups, beginning at 15 mg and tapering to 0 mg over 24 weeks. The primary outcome was GC-free remission, defined as a PMR activity score of < 10 and no systemic GC use, at week 52. Patients assigned to placebo had a higher median age than the MTX group (68 years vs 63 years) and a higher BMI (28 vs 25). The proportion of men and women enrolled in the study was approximately equal. Higher GC-Remission Rates in Less Time A total of 80% of patients in the MTX group achieved GC-free remission at 1 year compared with 46% of individuals in the placebo group ( P = .004). The median time to remission was shorter in the MTX group than in the placebo group (28 weeks vs 39 weeks; P = .013). The MTX group experienced fewer relapses through week 52 (31 vs 45). Relapse was determined by clinical judgement. From week 0 to 52, the median cumulative GC dose was 2050 mg (interquartile range, 1770-2583 mg) in the MTX group and 2288 (interquartile range, 1880-2878 mg) in the placebo group; this difference was not statistically significant ( P = .17). Adverse events were comparable between the two groups. 'We conclude that there is a significant effect of methotrexate 25 mg in recently diagnosed patients on GC-free remission, median time to remission, and the number of relapses, but we could not demonstrate a significant GC-sparing effect or an effect on percent of relapsing patients,' van der Maas said. Larger and Longer Study Needed Researchers are still following these patients, which will provide more insight on long-term GC use and prolonged remission, van der Maas said. The difference in GC-free remission rates between the two groups is 'pretty striking,' Tedeschi said, and the similarities in relapse rates and cumulative GC doses raise interesting questions that should be explored further. 'Based on these data, I do think it would be worthwhile to do a larger study.'
Medscape
25-06-2025
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- Medscape
Interferon-Driven Genes Signal Methotrexate Response in JIA
TOPLINE: Higher baseline expression of interferon (IFN)-driven genes was tied to a better response to methotrexate in patients with juvenile idiopathic arthritis. METHODOLOGY: Analysis of the link between blood biomarkers and response to methotrexate in 97 children (median age at baseline, 8.5 years; 62.9% women) with nonsystemic juvenile idiopathic arthritis (JIA). RNA sequencing was used to understand gene expression on CD4 + , CD8 + , CD14 + , and CD19 + cells and total peripheral blood mononuclear cells at baseline and at 6 months post-treatment with methotrexate. , CD8 , CD14 , and CD19 cells and total peripheral blood mononuclear cells at baseline and at 6 months post-treatment with methotrexate. The link between response to methotrexate therapy and gene activity in specific cell types was tested using the limma-voom, gene set enrichment analysis, and a new 51-gene score. Results were validated in 73 children with JIA, and pretreatment gene expression data were used to compare results with 240 adult patients with rheumatoid arthritis (RA). TAKEAWAY: Gene enrichment in the IFN-alpha (type I) and IFN-gamma (type II) response pathways was linked with treatment response in many cell types isolated from children with nonsystemic JIA. Higher baseline expression of both type I and type II IFN-driven genes was associated with a better response to methotrexate at 6 months post-treatment in JIA patients but not in adult RA patients. The 51-gene score, calculated from the expression levels of 51 specific IFN-response genes, was significantly higher in patients who responded to methotrexate than in those who did not (P = .00556). IN PRACTICE: 'It is possible that MTX [methotrexate] treatment is more effective in a distinct immunophenotype present across many International League of Associations for Rheumatology subtypes, where IFN-driven processes are dominant early in the disease,' the authors wrote. 'Our study provides proof of principle that carefully designed analyses can yield hope for a more precision-based approach to treatment in the future for children and families living with arthritis,' they added. SOURCE: This study was led by Melissa Kartawinata of University College London Great Ormond Street Institute of Child Health in London and Wei-Yu Lin of the University of Cambridge in Cambridge, both in England. It was published online on May 20, 2025, in Annals of the Rheumatic Diseases. LIMITATIONS: This study may have been underpowered to identify pathways with small but biologically significant influence on treatment response. Whole-blood RNA samples were unavailable to test the association between 51-IFN gene score and treatment response. Additionally, treatment response can fluctuate over time, and this study only analyzed outcomes at 6 months. DISCLOSURES: This study received support from the Medical Research Council, Versus Arthritis, Great Ormond Street Hospital Children's Charity, and Olivia's Vision. Additional support was provided by multiple organizations, including the Wellcome Trust and other sources. Several authors reported receiving funds and contributions in kind from various pharmaceutical companies. This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
Medscape
16-06-2025
- Health
- Medscape
Methotrexate Use Linked to Lower Infection Risk in Early RA
In patients with early rheumatoid arthritis (RA), methotrexate-based strategies were associated with a lower risk for serious infections compared with strategies using other conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Increasing age, smoking, and comorbidities were identified as important predictors of an increased risk for serious infections. METHODOLOGY: Researchers conducted an observational cohort study to assess the risk for serious infections among patients with early RA on the basis of prescribed treatment strategies. They used audit data of 17,472 adults with newly diagnosed RA (mean age, 59 years; 63% women) in England and Wales between May 2018 and April 2023. At 3 months, 63% of patients had initiated methotrexate-based therapy (either as monotherapy or in combination with another csDMARD), 26% had initiated other csDMARDs, and 11% had delayed initiating csDMARDs. Additionally, 79% were on concomitant corticosteroids as part of the initial treatment regimen. The primary outcome was a serious infection event, defined as an infection requiring hospitalization or resulting in death, assessed over a mean follow-up duration of 2.62 years. TAKEAWAY: The overall incidence rate of serious infections was 3.02 per 100 person-years; 41% of these infections were respiratory infections, followed by COVID (15%) and sepsis/bacteraemia (12%). Patients on methotrexate regimens had a 24% lower risk for serious infections than those on other csDMARDs (adjusted hazard ratio, 0.76; P < .001). < .001). Factors associated with an increased risk for serious infections included increasing age, current or past smoking, comorbidities (diabetes, lung disease, and hypertension), seropositivity for rheumatoid factor, and higher baseline disease severity ( P < .01 for all). < .01 for all). Patients who did not initiate csDMARDs at diagnosis had a higher incidence rate of serious infections than those who initiated csDMARDs. IN PRACTICE: "Channelling bias due to residual confounding is likely part of this explanation, but our data still suggest that avoidance of methotrexate because of concerns surrounding serious infection risk are not strongly supported by evidence," the authors wrote. SOURCE: This study was led by Maryam A. Adas, Centre for Rheumatic Disease, King's College London, London, England. It was published online on June 5, 2025, in Rheumatology . LIMITATIONS: Data on treatment with csDMARDs were available only at diagnosis and up to 3 months, preventing assessment of subsequent drug transitions or continuations. Certain confounding factors, such as the type or severity of lung disease, were not captured. Data on treatment adherence, steroid dosing, and the route of treatment administration were unavailable. DISCLOSURES: This study received no specific funding. One author reported receiving consulting fees and research grant income from pharmaceutical companies, including UCB and BMS. Several other authors reported receiving honoraria or speaker fees, holding positions, or having other financial ties with multiple companies.
