3 results on '"Doré, Caroline J."'
Search Results
2. Effectiveness of Belimumab After Rituximab in Systemic Lupus Erythematosus : A Randomized Controlled Trial.
- Author
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Shipa, Muhammad, Embleton-Thirsk, Andrew, Parvaz, Mariea, Santos, Liliana Ribeiro, Muller, Patrick, Chowdhury, Kashfia, Isenberg, David A., Doré, Caroline J., Gordon, Caroline, Ehrenstein, Michael R., Isenberg, David, D'Cruz, David P., Jordan, Natasha, Parker, Benjamin, Lightstone, Liz, Salama, Alan, Pyne, Debasish, Edwards, Christopher J., Griffiths, Bridget, and Vital, Edward M.
- Subjects
SYSTEMIC lupus erythematosus ,TALL-1 (Protein) ,BELIMUMAB ,RANDOMIZED controlled trials ,RITUXIMAB ,THERAPEUTIC use of monoclonal antibodies ,AUTOANTIBODIES ,RESEARCH ,RESEARCH methodology ,ARTHRITIS Impact Measurement Scales ,EVALUATION research ,COMPARATIVE studies ,BLIND experiment ,RESEARCH funding ,IMMUNOSUPPRESSIVE agents ,STATISTICAL sampling - Abstract
Background: B-cell depletion with rituximab is commonly used for patients with systemic lupus erythematosus (SLE) that is refractory to conventional therapy, but it yields variable responses. We hypothesized that high B-cell activating factor (BAFF) levels after rituximab can cause disease flares, thereby limiting its effectiveness.Objective: To obtain preliminary evidence for efficacy of the anti-BAFF therapeutic belimumab after rituximab in SLE.Design: Phase 2, randomized, double-blind (patients, assessors, researchers, care providers), placebo-controlled, parallel-group, superiority trial. (ISRCTN: 47873003).Setting: England.Participants: Fifty-two patients who had SLE that was refractory to conventional treatment and whose physicians had recommended rituximab therapy were recruited between 2 February 2017 and 28 March 2019.Intervention: Participants were treated with rituximab and 4 to 8 weeks later were randomly assigned (1:1) to receive intravenous belimumab or placebo for 52 weeks.Measurements: The prespecified primary end point was serum IgG anti-double-stranded DNA (anti-dsDNA) antibody levels at 52 weeks. Secondary outcomes included incidence of disease flares and adverse events.Results: At 52 weeks, IgG anti-dsDNA antibody levels were lower in patients treated with belimumab compared with placebo (geometric mean, 47 [95% CI, 25 to 88] vs. 103 [CI, 49 to 213] IU/mL; 70% greater reduction from baseline [CI, 46% to 84%]; P < 0.001). Belimumab reduced risk for severe flare (BILAG-2004 grade A) compared with placebo (hazard ratio, 0.27 [CI, 0.07 to 0.98]; log-rank P = 0.033), with 10 severe flares in the placebo group and 3 in the belimumab group. Belimumab did not increase incidence of serious adverse events. Belimumab significantly suppressed B-cell repopulation compared with placebo (geometric mean, 0.012 [CI, 0.006 to 0.014] vs. 0.037 [CI, 0.021 to 0.081] × 109/L) at 52 weeks in a subset of patients (n = 25) with available data.Limitations: Small sample size; biomarker primary end point.Conclusion: Belimumab after rituximab significantly reduced serum IgG anti-dsDNA antibody levels and reduced risk for severe flare in patients with SLE that was refractory to conventional therapy. The results suggest that this combination could be developed as a therapeutic strategy.Primary Funding Source: Versus Arthritis. [ABSTRACT FROM AUTHOR]- Published
- 2021
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3. Total Ankle Replacement Versus Arthrodesis for End-Stage Ankle Osteoarthritis: A Randomized Controlled Trial.
- Author
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Goldberg AJ, Chowdhury K, Bordea E, Hauptmannova I, Blackstone J, Brooking D, Deane EL, Bendall S, Bing A, Blundell C, Dhar S, Molloy A, Milner S, Karski M, Hepple S, Siddique M, Loveday DT, Mishra V, Cooke P, Halliwell P, Townshend D, Skene SS, Doré CJ, Brown R, Butler M, Chadwick C, Clough T, Cullen N, Davies M, Davies H, Harries B, Khoo M, Makwana N, Murty A, Najefi A, O'Donnell P, Raglan M, Thomas R, Torres P, Welck M, Winson I, and Zaidi R
- Subjects
- Male, Humans, Aged, Female, Ankle Joint surgery, Ankle surgery, State Medicine, Treatment Outcome, Arthrodesis adverse effects, Arthrodesis methods, Arthroplasty, Replacement, Ankle adverse effects, Arthroplasty, Replacement, Ankle methods, Osteoarthritis
- Abstract
Background: End-stage ankle osteoarthritis causes severe pain and disability. There are no randomized trials comparing the 2 main surgical treatments: total ankle replacement (TAR) and ankle fusion (AF)., Objective: To determine which treatment is superior in terms of clinical scores and adverse events., Design: A multicenter, parallel-group, open-label randomized trial. (ISRCTN registry number: 60672307)., Setting: 17 National Health Service trusts across the United Kingdom., Patients: Patients with end-stage ankle osteoarthritis, aged 50 to 85 years, and suitable for either procedure., Intervention: Patients were randomly assigned to TAR or AF surgical treatment., Measurements: The primary outcome was change in Manchester-Oxford Foot Questionnaire walking/standing (MOXFQ-W/S) domain scores between baseline and 52 weeks after surgery. No blinding was possible., Results: Between 6 March 2015 and 10 January 2019, a total of 303 patients were randomly assigned; mean age was 68 years, and 71% were men. Twenty-one patients withdrew before surgery, and 281 clinical scores were analyzed. At 52 weeks, the mean MOXFQ-W/S scores improved for both groups. The adjusted difference in the change in MOXFQ-W/S scores from baseline was -5.6 (95% CI, -12.5 to 1.4), showing that TAR improved more than AF, but the difference was not considered clinically or statistically significant. The number of adverse events was similar between groups (109 vs. 104), but there were more wound healing issues in the TAR group and more thromboembolic events and nonunion in the AF group. The symptomatic nonunion rate for AF was 7%. A post hoc analysis suggested superiority of fixed-bearing TAR over AF (-11.1 [CI, -19.3 to -2.9])., Limitation: Only 52-week data; pragmatic design creates heterogeneity of implants and surgical techniques., Conclusion: Both TAR and AF improve MOXFQ-W/S and had similar clinical scores and number of harms. Total ankle replacement had greater wound healing complications and nerve injuries, whereas AF had greater thromboembolism and nonunion, with a symptomatic nonunion rate of 7%., Primary Funding Source: National Institute for Health and Care Research Heath Technology Assessment Programme.
- Published
- 2022
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