SciCombinator

Discover the most talked about and latest scientific content & concepts.

Concept: Methotrexate

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Accompanying the increased use of biologic and non-biologic antirheumatic agents, patients with RA have been exposed to an increased risk of Pneumocystis jirovecii infection, which causes acute fulminant P. jirovecii pneumonia (PCP). Mortality in this population is higher than in HIV-infected individuals. Several guidelines and recommendations for HIV-infected individuals are available; however, such guidelines for RA patients remain less clear. Between 2006 and 2008 we encountered a clustering event of P. jirovecii infection among RA outpatients. Through our experience with this outbreak and a review of the recent medical literature regarding asymptomatic colonization and its clinical significance, transmission modes of infection and prophylaxis of PCP, we have learned the following lessons: PCP outbreaks among RA patients can occur through person-to-person transmission in outpatient facilities; asymptomatic carriers serve as reservoirs and sources of infection; and short-term prophylaxis for eradication of P. jirovecii is effective in controlling PCP outbreaks among RA outpatients.

Concepts: Epidemiology, Rheumatoid arthritis, Rheumatology, Methotrexate, Cyclophosphamide, Disease-modifying antirheumatic drug, Hydroxychloroquine, Sulfasalazine

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To compare the efficacy, safety, immunogenicity and pharmacokinetics (PK) of SB2 to the infliximab reference product (INF) in patients with moderate to severe rheumatoid arthritis (RA) despite methotrexate therapy.

Concepts: Rheumatoid arthritis, Rheumatology, Crohn's disease, Infliximab, Methotrexate, Ankylosing spondylitis, Psoriatic arthritis, Psoriasis

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Background Few blinded trials have compared conventional therapy consisting of a combination of disease-modifying antirheumatic drugs with biologic agents in patients with rheumatoid arthritis who have active disease despite treatment with methotrexate - a common scenario in the management of rheumatoid arthritis. Methods We conducted a 48-week, double-blind, noninferiority trial in which we randomly assigned 353 participants with rheumatoid arthritis who had active disease despite methotrexate therapy to a triple regimen of disease-modifying antirheumatic drugs (methotrexate, sulfasalazine, and hydroxychloroquine) or etanercept plus methotrexate. Patients who did not have an improvement at 24 weeks according to a prespecified threshold were switched in a blinded fashion to the other therapy. The primary outcome was improvement in the Disease Activity Score for 28-joint counts (DAS28, with scores ranging from 2 to 10 and higher scores indicating more disease activity) at week 48. Results Both groups had significant improvement over the course of the first 24 weeks (P=0.001 for the comparison with baseline). A total of 27% of participants in each group required a switch in treatment at 24 weeks. Participants in both groups who switched therapies had improvement after switching (P<0.001), and the response after switching did not differ significantly between the two groups (P=0.08). The change between baseline and 48 weeks in the DAS28 was similar in the two groups (-2.1 with triple therapy and -2.3 with etanercept and methotrexate, P=0.26); triple therapy was noninferior to etanercept and methotrexate, since the 95% upper confidence limit of 0.41 for the difference in change in DAS28 was below the margin for noninferiority of 0.6 (P=0.002). There were no significant between-group differences in secondary outcomes, including radiographic progression, pain, and health-related quality of life, or in major adverse events associated with the medications. Conclusions With respect to clinical benefit, triple therapy, with sulfasalazine and hydroxychloroquine added to methotrexate, was noninferior to etanercept plus methotrexate in patients with rheumatoid arthritis who had active disease despite methotrexate therapy. (Funded by the Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development, and others; CSP 551 RACAT ClinicalTrials.gov number, NCT00405275 .).

Concepts: Medicine, Rheumatoid arthritis, Rheumatology, Methotrexate, Ankylosing spondylitis, Psoriatic arthritis, Disease-modifying antirheumatic drug, Hydroxychloroquine

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Survival for children and young adults with high-risk B-acute lymphoblastic leukemia has improved significantly, but 20% to 25% of patients are not cured. Children’s Oncology Group study AALL0232 tested two interventions to improve survival.

Concepts: Improve, Methotrexate, Acute lymphoblastic leukemia

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To assess the efficacy and safety of switching from the infliximab reference product (RP; Remicade) to its biosimilar CT-P13 (Remsima, Inflectra) or continuing CT-P13 in patients with rheumatoid arthritis (RA) for an additional six infusions.

Concepts: Rheumatoid arthritis, Rheumatology, Infliximab, Methotrexate, Ankylosing spondylitis, Psoriatic arthritis, Etanercept, Adalimumab

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To compare persistence and adherence to triple therapy with nonbiologic disease-modifying antirheumatic drugs (DMARDs) methotrexate (MTX), hydroxychloroquine, and sulfasalazine, versus a tumor necrosis factor inhibitor plus MTX (TNFi+MTX) in patients with rheumatoid arthritis (RA).

Concepts: Rheumatoid arthritis, Methotrexate, Arthritis, Tumor necrosis factor-alpha, Ankylosing spondylitis, Disease-modifying antirheumatic drug, Hydroxychloroquine, Sulfasalazine

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BACKGROUND: Roughly a third of patients with rheumatoid arthritis treated with biological treatments receive them as monotherapy. Tocilizumab-an inhibitor of interleukin 6 receptor signalling-has been studied as monotherapy in several clinical trials. We assessed the efficacy and safety of tocilizumab monotherapy compared with adalimumab monotherapy for patients with rheumatoid arthritis. METHODS: We did this randomised, double-blind, parallel-group, phase 4 superiority study in 76 centres in 15 countries in North and South America, Australasia, and Europe. We enrolled patients who were aged at least 18 years, had severe rheumatoid arthritis for 6 months or more, and were intolerant to methotrexate or were inappropriate for continued methotrexate treatment. Patients were randomly assigned (1:1; block size of four) to receive tocilizumab 8 mg per kg bodyweight intravenously every 4 weeks plus placebo subcutaneously every 2 weeks or adalimumab 40 mg per kg bodyweight subcutaneously every 2 weeks plus placebo intravenously every 4 weeks for 24 weeks. Investigators, patients, and sponsor personnel were masked to assignment. The primary endpoint was change in disease activity score using 28 joints (DAS28) from baseline to week 24. This trial is registered with ClinicalTrials.gov, number NCT01119859. FINDINGS: We screened 452 patients and enrolled 326 patients. The intention-to-treat population contained 325 patients (163 assigned to tocilizumab, 162 assigned to adalimumab). Week 24 mean change from baseline in DAS28 was significantly greater in the tocilizumab group (-3·3) than in the adalimumab group (-1·8) patients (difference -1·5, 95% CI -1·8 to -1·1; p<0·0001). 16 of 162 (10%) patients in the adalimumab group versus 19 of 162 (12%) in the tocilizumab group had serious adverse events. More patients in the tocilizumab group than in the adalimumab group had increased LDL-cholesterol, increased alanine aminotransferase concentrations, and reduced platelet and neutrophil counts. INTERPRETATION: Tocilizumab monotherapy was superior to adalimumab monotherapy for reduction of signs and symptoms of rheumatoid arthritis in patients for whom methotrexate was deemed inappropriate. The adverse event profiles of tocilizumab and adalimumab were consistent with previous findings. FUNDING: F Hoffmann-La Roche.

Concepts: Clinical trial, Rheumatoid arthritis, Rheumatology, Infliximab, Methotrexate, Ankylosing spondylitis, Psoriatic arthritis, Serious adverse event

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To investigate whether methotrexate or tumour necrosis factor inhibitors (TNFi) affect osteophyte formation in patients with psoriatic arthritis (PsA).

Concepts: Rheumatoid arthritis, Infliximab, Methotrexate, Arthritis, Psoriatic arthritis, Psoriasis

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OBJECTIVE: To evaluate homocysteine levels in patients with Takayasu arteritis (TA) and in controls, and to analyze associations between homocysteine levels and paraoxonase 1 (PON1) activity, cysteine levels, methotrexate use, disease activity, extent of arterial involvement, and ischemic events in patients with TA. METHODS: A cross-sectional study was performed with 29 patients with TA and 30 controls who underwent clinical evaluation and blood sample collection in the fasting state. RESULTS: Among patients with TA, active disease was observed in 9 (31.0%) and previous arterial ischemic events in 10 (34.5%). Therapy with methotrexate was prescribed to 9 (31.0%) patients and it was associated with folic acid in 8 cases. Median homocysteine level was higher in patients with TA [10.9 μmol/l, interquartile range (IQR) 9.6-14.8] than in controls (6.9 μmol/l, IQR 5.1-11.9; p < 0.001). No difference was found regarding mean homocysteine levels between those using methotrexate and those under other therapies (12.8 ± 5.3 μmol/l vs 12.1 ± 3.2 μmol/l, respectively; p = 0.662). TA patients with active disease presented lower homocysteine levels (10.4 ± 2.1 μmol/l) compared to TA patients in remission (13.1 ± 4.2 μmol/l) (p = 0.034). A significant correlation was found between cysteine and homocysteine levels in patients with TA (ρ = 0.676, p < 0.0001), while there was no correlation between homocysteine and PON1 activity (ρ = 0.214, p = 0.265). Median homocysteine levels were higher in patients with ischemic events (13.2 μmol/l, IQR 10.9-17.5) compared to patients with no ischemic events (9.8 μmol/l, IQR 8.7-14.7; p = 0.027) and were associated with arterial ischemia in patients with TA (OR 1.31, 95% CI 1.01-1.71, p = 0.041). CONCLUSION: Patients with TA presented higher homocysteine levels than controls and homocysteine was associated with an increased risk of arterial ischemic events in TA.

Concepts: Median, Interquartile range, Folic acid, Methotrexate, Homocysteine, PON1, Paraoxonase, Takayasu's arteritis

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