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Therapeutic options for patients with rare rheumatic diseases: a systematic review and meta-analysis.

ABSTRACT: BACKGROUND:Rare diseases (RDs) in rheumatology as a group have a high prevalence, but randomized controlled trials are hampered by their heterogeneity and low individual prevalence. To survey the current evidence of pharmacotherapies for rare rheumatic diseases, we conducted a systematic review and meta-analysis. Randomized controlled trials (RCTs) of RDs in rheumatology for different pharmaco-interventions were included into this meta-analysis if there were two or more trials investigating the same RD and using the same assessment tools or outcome parameters. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PUBMED were searched up to April 2nd 2020. The overall objective of this study was to identify RCTs of RDs in rheumatology, evaluate the overall quality of these studies, outline the evidence of pharmacotherapy, and summarize recommended therapeutic regimens. RESULTS:We screened 187 publications, and 50 RCTs met our inclusion criteria. In total, we analyzed data of 13 different RDs. We identified several sources of potential bias, such as a lack of description of blinding methods and allocation concealment, as well as small size of the study population. Meta-analysis was possible for 26 studies covering six RDs: Hunter disease, Behçet's disease, giant cell arteritis, ANCA-associated vasculitis, reactive arthritis, and systemic sclerosis. The pharmacotherapies tested in these studies consisted of immunosuppressants, such as corticosteroids, methotrexate and azathioprine, or biologicals. We found solid evidence for idursulfase as a treatment for Hunter syndrome. In Behçet's disease, apremilast and IF-? showed promising results with regard to total and partial remission, and Tocilizumab with regard to relapse-free remission in giant cell arteritis. Rituximab, cyclophosphamide, and azathioprine were equally effective in ANCA-associated vasculitis, while mepolizumab improved the efficacy of glucocorticoids. The combination of rifampicin and azithromycin showed promising results in reactive arthritis, while there was no convincing evidence for the efficacy of pharmacotherapy in systemic sclerosis. CONCLUSION:For some diseases such as systemic sclerosis, ANCA-associated vasculitis, or Behcet's disease, higher quality trials were available. These RCTs showed satisfactory efficacies for immunosuppressants or biological drugs, except for systemic sclerosis. More high quality RCTs are urgently warranted for a wide spectrum of RDs in rheumatology.

SUBMITTER: Bender TTA

PROVIDER: S-EPMC7603763 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Therapeutic options for patients with rare rheumatic diseases: a systematic review and meta-analysis.

Bender Tim T A TTA Leyens Judith J Sellin Julia J Kravchenko Dmitrij D Conrad Rupert R Mücke Martin M Seidel Matthias F MF

Orphanet journal of rare diseases 20201031 1

<h4>Background</h4>Rare diseases (RDs) in rheumatology as a group have a high prevalence, but randomized controlled trials are hampered by their heterogeneity and low individual prevalence. To survey the current evidence of pharmacotherapies for rare rheumatic diseases, we conducted a systematic review and meta-analysis. Randomized controlled trials (RCTs) of RDs in rheumatology for different pharmaco-interventions were included into this meta-analysis if there were two or more trials investigat ...[more]

PMID: 33129321

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Project description:ObjectivesThe impact of rheumatic diseases on COVID-19 infection remains poorly investigated. Here we performed a systematic review and meta-analysis to evaluate the outcomes of COVID-19 in patients with rheumatic diseases.MethodsWe systematically searched PubMed, Embase, Cochrane Library, Scopus and preprint database up to 29th August 2020, for publications with confirmed COVID-19 infection in patients with rheumatic diseases. The primary outcomes were the rates of hospitalization, oxygen support, intensive care unit (ICU) admission and death. A meta-analysis of effect sizes using the random-effects models was performed, and meta-regression analyses were performed to explore heterogeneity. The data from the COVID-19 Global Rheumatology Alliance physician registry (the COVID-19 GRA) was used as a reference.ResultsA total of 31 articles involving 1138 patients were included in this systematic review and meta-analysis. The publications were from Europe, Asia and North America, but none from other continents. The overall rates of hospitalization, oxygen support, ICU admission and fatality among COVID-19 infected patients with rheumatic diseases were 0.58 (95% confidence interval (CI) 0.48-0.67), 0.33 (95% CI 0.21-0.47), 0.09 (95% CI 0.05-0.15) and 0.07 (95% CI 0.03-0.11), respectively. The rate of oxygen support in Europe (0.48, 95% CI 0.4-0.57) was higher than that in other continents. Among all hospitalized patients, the rates of oxygen support, ICU admission and fatality were 0.61 (95% CI 0.48-0.73), 0.13 (95% CI 0.07-0.21) and 0.13 (95% CI 0.09-0.18), respectively. The fatality rate was highest in Europe (0.19, 95% CI 0.15-0.24). The fatality rate was higher both in this meta-analysis and the COVID-19 GRA (7.0% and 6.7%, respectively) than that (3.4%) in WHO database, although the age, gender and comorbidity were not matched.ConclusionPatients with rheumatic diseases remain vulnerable with substantial rates of severe outcomes and a geographic variation. More studies were urgently needed to elucidate the risk factors of severe outcomes in this population.

Project description:There is an increasing interest in the pathophysiological role of the kynurenine pathway of tryptophan metabolism in the regulation of immune function and inflammation. We sought to address the link between this pathway and the presence rheumatic diseases (RD) by conducting a systematic review and meta-analysis of studies reporting the plasma or serum concentrations of tryptophan, kynurenine, and other relevant metabolites in RD patients and healthy controls. We searched electronic databases for relevant articles published between inception and the 30th of June 2023. Risk of bias and certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and the Grades of Recommendation, Assessment, Development and Evaluation Working Group system. In 24 studies selected for analysis, compared to controls, RD patients had significantly lower tryptophan (standard mean difference, SMD= -0.71, 95% CI -1.03 to -0.39, p<0.001; I2 = 93.6%, p<0.001; low certainty of evidence), and higher kynurenine (SMD=0.69, 95% CI 0.35 to 1.02, p<0.001; I2 = 93.2%, p<0.001; low certainty), kynurenine to tryptophan ratios (SMD=0.88, 95% CI 0.55 to 1.21, p<0.001; I2 = 92.9%, p<0.001; moderate certainty), 3-hydroxykynurenine (SMD=0.74, 95% CI 0.30 to 1.18, p=0.001; I2 = 87.7%, p<0.001; extremely low certainty), and quinolinic acid concentrations (SMD=0.71, 95% CI 0.31 to 1.11, p<0.001; I2 = 88.1%, p<0.001; extremely low certainty). By contrast, there were non-significant between-group differences in kynurenic acid, 3-hydroxyanthranilic acid, kynurenic acid to kynurenine ratio, or quinolinic acid to kynurenine acid ratio. In meta-regression, the SMD of tryptophan, kynurenine, and kynurenine to tryptophan ratio were not associated with age, publication year, sample size, RD duration, C-reactive protein, or use of anti-rheumatic drugs and corticosteroids. In subgroup analysis, the SMD of tryptophan, kynurenine, and kynurenine to tryptophan ratio was significant across different types of RD, barring rheumatoid arthritis. Therefore, we have observed significant alterations in tryptophan, kynurenine, 3-hydroxykynurenine, and quinolinic acid concentrations in RD patients. Further research is warranted to determine whether these biomarkers can be useful for diagnosis and management in this patient group. (PROSPERO registration number: CRD CRD42023443718).Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD CRD42023443718.

Project description:In clinical practice guidelines, there is no consensus about the medications that should be initially offered to patients with brucellosis. To provide informative evidence, we compared and ranked brucellosis medications based on their efficacy and safety. For this systematic review and network meta-analysis, we searched 4 English databases and 3 Chinese databases, from the date of database inception to December 13, 2023. We included randomized controlled trials (RCTs) involving children and adolescents with brucellosis, comparing different antibiotic regimens. We excluded studies explicitly targeting patients with spondylitis brucellosis, endocarditis brucellosis, and neuro-brucellosis. The primary outcomes were overall failure (efficacy) and side effects (safety). Secondary outcomes were relapse and therapeutic failure. Pairwise meta-analysis was first examined. Data were analyzed using random effects network meta-analysis, with subgroup and sensitivity analyses performed. The Confidence in Network Meta-Analysis (CINeMA) framework was used to assess the certainty of evidence. The protocol was preregistered in PROSPERO (CRD42023491331). Of the 11,747 records identified through the database search, 43 RCTs were included in the network meta-analysis. Compared with standard therapy (Doxycycline + Rifampicin), Rifampicin + Tetracyclines (RR 4.96; 95% CI 1.47 to 16.70; very low certainty of evidence), Doxycycline + TMP/SMX (RR 0.18; 95% CI 0.06 to 0.52; low certainty of evidence), Doxycycline + Quinolones (RR 0.27; 95% CI 0.11 to 0.71; low certainty of evidence), Streptomycin + Tetracyclines (RR 0.04; 95% CI 0.01 to 0.16; low certainty of evidence), and Single (RR 0.05; 95% CI 0.02 to 0.16; moderate certainty of evidence) were less efficacious. Doxycycline + Gentamicin ranked the best in efficacy (SUCRA values: 0.94), the second is Triple (SUCRA values: 0.87), and the third is Doxycycline + Streptomycin (SUCRA values: 0.78). Brucellosis medications differ in efficacy and safety. Doxycycline + Gentamicin, Triple, and Doxycycline + Streptomycin have superior efficacy and safety. Treatment of brucellosis should strike a balance between efficacy, safety, and cost.

Project description:Osteocytes are the most abundant (~95%) cells in bone with the longest half-life (~25 years) in humans. In the past osteocytes have been regarded as vestigial cells in bone, since they are buried inside the tough bone matrix. However, during the last 30 years it has become clear that osteocytes are as important as bone forming osteoblasts and bone resorbing osteoclasts in maintaining bone homeostasis. The osteocyte cell body and dendritic processes reside in bone in a complex lacuno-canalicular system, which allows the direct networking of osteocytes to their neighboring osteocytes, osteoblasts, osteoclasts, bone marrow, blood vessels, and nerves. Mechanosensing of osteocytes translates the applied mechanical force on bone to cellular signaling and regulation of bone adaptation. The osteocyte lacuno-canalicular system is highly efficient in transferring external mechanical force on bone to the osteocyte cell body and dendritic processes via displacement of fluid in the lacuno-canalicular space. Osteocyte mechanotransduction regulates the formation and function of the osteoblasts and osteoclasts to maintain bone homeostasis. Osteocytes produce a variety of proteins and signaling molecules such as sclerostin, cathepsin K, Wnts, DKK1, DMP1, IGF1, and RANKL/OPG to regulate osteoblast and osteoclast activity. Various genetic abnormality-associated rare bone diseases are related to disrupted osteocyte functions, including sclerosteosis, van Buchem disease, hypophosphatemic rickets, and WNT1 and plastin3 mutation-related disorders. Meticulous studies during the last 15 years on disrupted osteocyte function in rare bone diseases guided for the development of various novel therapeutic agents to treat bone diseases. Studies on genetic, molecular, and cellular mechanisms of sclerosteosis and van Buchem disease revealed a role for sclerostin in bone homeostasis, which led to the development of the sclerostin antibody to treat osteoporosis and other bone degenerative diseases. The mechanism of many other rare bone diseases and the role of the osteocyte in the development of such conditions still needs to be investigated. In this review, we mainly discuss the knowledge obtained during the last 30 years on the role of the osteocyte in rare bone diseases. We speculate about future research directions to develop novel therapeutic drugs targeting osteocyte functions to treat both common and rare bone diseases.

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Therapeutic options for patients with rare rheumatic diseases: a systematic review and meta-analysis.

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Therapeutic options for patients with rare rheumatic diseases: a systematic review and meta-analysis.

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