Latest news with #methotrexate
Medscape
03-07-2025
- Health
- 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
- Health
- 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.
Medscape
06-06-2025
- Health
- Medscape
Year-Long Methotrexate Not Helpful for Inflammatory Knee OA
Compared with placebo, low-dose methotrexate administered weekly at doses up to 15 mg for 52 weeks did not relieve knee pain or reduce the size of effusion-synovitis in patients with inflammatory knee osteoarthritis (OA). METHODOLOGY: Researchers in China conducted a multicenter, clinical trial between July 2019 and January 2023 to examine whether low-dose methotrexate can reduce knee pain and effusion-synovitis in knee OA. They included 215 patients (mean age, 60.6 years; 89% women) with inflammatory knee OA and effusion-synovitis who were randomly assigned to receive either methotrexate or placebo, with weekly 5 mg folic acid supplementation given 1 day after treatment. Participants continued their regular medications (except corticosteroids and anti-synovitis drugs), did not take trimethoprim, and avoided alcohol during the trial. Primary outcomes were changes in knee pain on the visual analog scale (VAS) and inflammation measured by the effusion-synovitis maximal area on MRI over 52 weeks. Secondary outcomes were assessment of pain, stiffness, and physical function; changes in infrapatellar fat pad signal intensity; and evaluation of response to the assigned treatment. TAKEAWAY: At week 52, no significant difference was found between methotrexate and placebo groups in terms of VAS pain and effusion-synovitis maximal area (between-group difference, 0.3 mm; 95% CI, -6.7 to 7.3 mm and 0.1 cm 2 ; 95% CI, -0.8 to 1.0 cm 2 , respectively). ; 95% CI, -0.8 to 1.0 cm , respectively). No significant differences were observed between the two groups in terms of any of the prespecified secondary outcomes. The frequency of experiencing at least one adverse event was comparable between the methotrexate and placebo groups (29.6% and 24.3%, respectively); however, elevated concentrations of liver enzymes were more common in the methotrexate group. IN PRACTICE: 'Given the lack of efficacy of MTX [methotrexate] across knee OA studies and the known potential adverse events, it is not recommended for the treatment of painful, inflammatory knee OA. We now need to focus our attention on treatments that can both inhibit joint inflammation and stimulate chondrocytes within the cartilage to synthesize replacement matrix. The future of pharmaceuticals for knee OA needs to move past MTX,' Nancy E. Lane, MD, UC Davis Health, Sacramento, California, wrote in an accompanying editorial. SOURCE: This study was led by Zhaohua Zhu, PhD, Zhujiang Hospital, Southern Medical University, Guangzhou, China. It was published online on June 2, 2025, in JAMA Internal Medicine . LIMITATIONS: This study was conducted during COVID-19 shutdowns, which delayed recruitment and potentially increased loss to follow-up and nonadherence rates. The findings may not be fully generalizable because most participants were women, and racial and ethnic diversity was limited. The relatively small number of participants in each subgroup may have limited the ability to detect significant benefits in specific populations. DISCLOSURES: This study received funding from the National Key Research and Development Program of China, the National Natural Science Foundation of China, and the Clinical Research Startup Program of Southern Medical University. One author reported providing consulting advice on scientific advisory boards for various pharmaceutical companies outside the submitted work.
Medscape
03-06-2025
- Business
- Medscape
Tocilizumab, Alone or With Methotrexate, Potent in Active RA
Subcutaneous tocilizumab, either as monotherapy or in combination with methotrexate, demonstrated greater efficacy than methotrexate alone and was well tolerated in patients with active rheumatoid arthritis (RA) who had an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). METHODOLOGY: Researchers conducted a phase 3 trial at 19 sites in China between July 2017 and August 2022 to evaluate the efficacy of subcutaneous tocilizumab, administered either as monotherapy or in combination with methotrexate, in 340 patients with moderate to severe active RA (mean age, 47.5 years; 86.5% women). The patients had a diagnosis of RA for ≥ 6 months, had received methotrexate for ≥ 12 weeks, experienced treatment failure with at least one csDMARD (including methotrexate), had at least six swollen joints and at least eight tender joints, and had either a high-sensitivity C-reactive protein level ≥ 4 mg/L or an erythrocyte sedimentation rate ≥ 28 mm/h. Patients were randomly assigned to receive tocilizumab-methotrexate combination therapy (n = 136), tocilizumab monotherapy with placebo (n = 136), or methotrexate monotherapy with placebo (n = 68) for 24 weeks. Tocilizumab (162 mg) was administered subcutaneously once every 2 weeks, and methotrexate (10-25 mg) was administered orally once every week. Patients achieving a Disease Activity Score in 28 joints of ≤ 3.2 after 24 weeks continued their randomly assigned treatment, whereas those with a score > 3.2 switched to unblinded tocilizumab-methotrexate treatment. The primary efficacy endpoint was the proportion of patients who achieved a ≥ 20% improvement in the American College of Rheumatology (ACR20) response criteria at 24 weeks, with long-term efficacy analyzed at 48 weeks and safety monitored for 56 weeks. TAKEAWAY: The ACR20 response rate at 24 weeks was higher in the tocilizumab-methotrexate combination therapy (52.9%) and tocilizumab monotherapy (50.0%) groups than in the methotrexate monotherapy group (25.0%), with significant differences of 27.9 and 25.0 percentage points, respectively ( P < .001 for both). < .001 for both). Long-term efficacy analysis at 48 weeks showed maintained or improved efficacy in patients continuing tocilizumab monotherapy or tocilizumab-methotrexate combination therapy, with an improved disease status in those who switched to unblinded tocilizumab-methotrexate treatment at 24 weeks. Tocilizumab was well tolerated as both monotherapy and in combination with methotrexate, with no new safety signals. IN PRACTICE: 'Subcutaneous tocilizumab, both as monotherapy and in combination with methotrexate, had clinically significant efficacy compared with methotrexate monotherapy in Chinese patients with moderate to severe active RA,' the authors wrote. SOURCE: This study was led by Tian Liu, MD, Peking University People's Hospital in Beijing, China. It was published online on May 19, 2025, in JAMA Network Open . LIMITATIONS: Only Chinese patients were included, thus limiting the generalizability of the findings. Researchers did not include imaging analysis. The recruitment was extended over a period of 4 years owing to the COVID-19 pandemic, which resulted in missing the efficacy assessments and tocilizumab administration in some patients. DISCLOSURES: This study received funding from and was conducted in collaboration with F. Hoffmann-La Roche Ltd. Three authors reported receiving grants from various pharmaceutical companies, including Roche. Two authors reported being employed by Roche (China) Holding.
