First name
George
Middle name
A
Last name
Tomlinson

Title

The Childhood Arthritis & Rheumatology Research Alliance Start Time Optimization of Biologics in Polyarticular Juvenile Idiopathic Arthritis Study

Year of Publication

2021

Number of Pages

Date Published

2021 Jun 08

ISSN Number

2326-5205

Abstract

<p><strong>BACKGROUND: </strong>The optimal time to start biologics for polyarticular JIA (pJIA) remains uncertain. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed 3 consensus treatment plans (CTPs) for untreated pJIA to compare strategies for starting biologics.</p>

<p><strong>METHODS: </strong>Start Time Optimization of biologics in PJIA (STOP-JIA) was a prospective, observational, CARRA Registry study comparing the effectiveness of: 1) Step Up (SU)- initial non-biologic disease modifying anti-rheumatic drug (DMARD) monotherapy, adding biologic if needed; 2) Early Combination (EC)- DMARD and biologic started together; 3) Biologic First (BF)- biologic monotherapy. The primary outcome was clinically inactive disease (CID) (Wallace) off glucocorticoids at 12 months. Secondary outcomes included PROMIS® pain interference and mobility, inactive disease defined by the clinical Juvenile Arthritis Disease Activity Score (cJADAS10 ID) and pediatric ACR70 (pACR70).</p>

<p><strong>RESULTS: </strong>Of 400 patients enrolled, 257 (64%) began SU, 100 (25%) EC and 43 (11%) BF. After propensity score weighting and multiple imputation, 37% of EC, 32% SU and 24% BF achieved ACR CID (p=0.17). cJADAS10 ID (score ≤2.5) also favored EC over SU (59% versus 43%; p=0.03) as did pACR70 results (80% versus 64%; p=0.008) but generalizability is limited by missing data. PROMIS® measures improved in all groups, but without significant differences. Seventeen serious adverse events were reported (mostly infections).</p>

<p><strong>CONCLUSIONS: </strong>Achievement of CID off GC did not significantly differ between groups at 12 months. While there was a statistically significant higher likelihood of EC achieving cJADAS10 ID and pACR70, these results require further exploration.</p>

DOI

10.1002/art.41888

Alternate Title

Arthritis Rheumatol

PMID

34105312
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Title

Efficacy of antibiotic prophylaxis in patients with cancer and hematopoietic stem cell transplantation recipients: A systematic review of randomized trials.

Year of Publication

2019

Number of Pages

Date Published

2019 Jul 05

ISSN Number

2045-7634

Abstract

<p><strong>PURPOSE: </strong>To determine the efficacy and safety of different prophylactic systemic antibiotics in adult and pediatric patients receiving chemotherapy or undergoing hematopoietic stem cell transplantation (HSCT).</p>

<p><strong>METHODS: </strong>We conducted a systematic review and performed searches of Ovid MEDLINE, MEDLINE in-process and Embase; and Cochrane Central Register of Controlled Trials. Studies were included if patients had cancer or were HSCT recipients with anticipated neutropenia, and the intervention was systemic antibacterial prophylaxis. Strategies synthesized included fluoroquinolone vs no antibiotic/nonabsorbable antibiotic; fluoroquinolone vs trimethoprim-sulfamethoxazole; trimethoprim-sulfamethoxazole vs no antibiotic; and cephalosporin vs. no antibiotic. Fluoroquinolone vs cephalosporin and levofloxacin vs ciprofloxacin were compared by network meta-analysis. Primary outcome was bacteremia.</p>

<p><strong>RESULTS: </strong>Of 20&nbsp;984 citations screened, 113 studies comparing prophylactic antibiotic to control were included. The following were effective in reducing bacteremia: fluoroquinolone vs no antibiotic/nonabsorbable antibiotic (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.41-0.76), trimethoprim-sulfamethoxazole vs no antibiotic (RR 0.59, 95% CI 0.41-0.85) and cephalosporin vs no antibiotic (RR 0.30, 95% CI 0.16-0.58). Fluoroquinolone was not significantly associated with increased Clostridium difficile infection (RR 0.62, 95% CI 0.31-1.24) or invasive fungal disease (RR 1.28, 95% CI 0.79-2.08) but did increase resistance to fluoroquinolone among bacteremia isolates (RR 3.35, 95% CI 1.12 to 10.03). Heterogeneity in fluoroquinolone effect on bacteremia was not explained by evaluated study, population, or methodological factors. Network meta-analysis revealed no direct comparisons for pre-specified analyses; superior regimens were not identified.</p>

<p><strong>CONCLUSIONS: </strong>Fluoroquinolone, trimethoprim-sulfamethoxazole, and cephalosporin prophylaxis reduced bacteremia. A clinical practice guideline to facilitate prophylactic antibiotic decision-making is required.</p>

DOI

10.1002/cam4.2395

Alternate Title

Cancer Med

PMID

31274245
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Title

The Childhood Arthritis & Rheumatology Research Alliance Consensus Treatment Plans: Towards Comparative Effectiveness in the Pediatric Rheumatic Diseases.

Year of Publication

2018

Number of Pages

Date Published

2018 Jan 15

ISSN Number

2326-5205

Abstract

<p>The pediatric rheumatic diseases are a heterogeneous group of rare diseases, posing a number of challenges for the use of traditional clinical and translational research approaches. Innovative comparative effectiveness approaches are needed to efficiently study treatment approaches and disease outcomes. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed the consensus treatment plan (CTP) approach as a comparative effectiveness tool for research in pediatric rheumatology. CTPs are treatment strategies, developed by consensus methods among CARRA members, intended to reduce variation in treatment approaches, standardize outcome measurements, and allow for comparison of the effectiveness of different approaches with the goal of improving disease outcomes. To date, CTPs have been published for 7 different diseases and disease manifestations. The approach has been successfully piloted for juvenile localized scleroderma, systemic onset juvenile idiopathic arthritis (JIA), polyarticular JIA, dermatomyositis, and lupus nephritis. Large-scale studies are underway for systemic JIA and polyarticular JIA, with the CARRA patient registry serving as the data collection platform. These studies have been designed with stakeholder involvement, including active input from CARRA providers, patients, and parents, with the goal of increasing the feasibility and ensuring the relevance of the outcomes. These studies include ancillary biospecimen collection intended to support additional translational and mechanistic studies. Data from these ongoing CTP studies will provide more information on the ability of this approach to identify effective treatment strategies and improve outcomes for the pediatric rheumatic diseases. This article is protected by copyright. All rights reserved.</p>

DOI

10.1002/art.40395

Alternate Title

PMID

29333701
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