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JAMA Neurology Nov 2023Emerging evidence suggests that progression independent of relapse activity (PIRA) is a substantial contributor to long-term disability accumulation in...
IMPORTANCE
Emerging evidence suggests that progression independent of relapse activity (PIRA) is a substantial contributor to long-term disability accumulation in relapsing-remitting multiple sclerosis (RRMS). To date, there is no uniform agreed-upon definition of PIRA, limiting the comparability of published studies.
OBJECTIVE
To summarize the current evidence about PIRA based on a systematic review, to discuss the various terminologies used in the context of PIRA, and to propose a harmonized definition for PIRA for use in clinical practice and future trials.
EVIDENCE REVIEW
A literature search was conducted using the search terms multiple sclerosis, PIRA, progression independent of relapse activity, silent progression, and progression unrelated to relapses in PubMed, Embase, Cochrane, and Web of Science, published between January 1990 and December 2022.
FINDINGS
Of 119 identified single records, 48 eligible studies were analyzed. PIRA was reported to occur in roughly 5% of all patients with RRMS per annum, causing at least 50% of all disability accrual events in typical RRMS. The proportion of PIRA vs relapse-associated worsening increased with age, longer disease duration, and, despite lower absolute event numbers, potent suppression of relapses by highly effective disease-modifying therapy. However, different studies used various definitions of PIRA, rendering the comparability of studies difficult.
CONCLUSION AND RELEVANCE
PIRA is the most frequent manifestation of disability accumulation across the full spectrum of traditional MS phenotypes, including clinically isolated syndrome and early RRMS. The harmonized definition suggested here may improve the comparability of results in current and future cohorts and data sets.
Topics: Humans; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Chronic Disease; Recurrence; PubMed; Disease Progression
PubMed: 37782515
DOI: 10.1001/jamaneurol.2023.3331 -
RMD Open Aug 2023Through this systematic literature review, we assembled evidence to inform the EULAR recommendations for the non-pharmacological management of systemic lupus... (Review)
Review
Through this systematic literature review, we assembled evidence to inform the EULAR recommendations for the non-pharmacological management of systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). We screened articles published between January 2000 and June 2021. Studies selected for data extraction (118 for SLE and 92 for SSc) were thematically categorised by the character of their intervention. Of 208 articles included, 51 were classified as robust in critical appraisal. Physical activity was the most studied management strategy and was found to be efficacious in both diseases. Patient education and self-management also constituted widely studied topics. Many studies on SLE found psychological interventions to improve quality of life. Studies on SSc found phototherapy and laser treatment to improve cutaneous disease manifestations. In summary, non-pharmacological management of SLE and SSc encompasses a wide range of interventions, which can be combined and provided either with or without adjunct pharmacological treatment but should not aim to substitute the latter when this is deemed required. While some management strategies i.e., physical exercise and patient education, are already established in current clinical practice in several centres, others e.g., phototherapy and laser treatment, show both feasibility and efficacy, yet require testing in more rigorous trials than those hitherto conducted.
Topics: Humans; Quality of Life; Scleroderma, Systemic; Lupus Erythematosus, Systemic
PubMed: 37532469
DOI: 10.1136/rmdopen-2023-003297 -
RMD Open Aug 2023To identify the best evidence on the efficacy of non-pharmacological interventions in reducing fatigue in people with inflammatory rheumatic and musculoskeletal diseases...
Efficacy of non-pharmacological interventions: a systematic review informing the 2023 EULAR recommendations for the management of fatigue in people with inflammatory rheumatic and musculoskeletal diseases.
OBJECTIVE
To identify the best evidence on the efficacy of non-pharmacological interventions in reducing fatigue in people with inflammatory rheumatic and musculoskeletal diseases (I-RMDs) and to summarise their safety in the identified studies to inform European Alliance of Associations for Rheumatology recommendations for the management of fatigue in people with I-RMDs.
METHODS
Systematic review of randomised controlled trials (RCTs) including adults with I-RMDs conducted according to the Cochrane Handbook. Search strategy ran in Medline, Embase, Cochrane Library, CINAHL Complete, PEDro, OTseeker and PsycINFO. Assessment of risk of bias, data extraction and synthesis were performed by two reviewers independently. Data were pooled in meta-analyses.
RESULTS
From a total of 4150 records, 454 were selected for full-text review, 82 fulfilled the inclusion criteria and 55 RCTs were included in meta-analyses. Physical activity or exercise was efficacious in reducing fatigue in rheumatoid arthritis (RA) (standardised mean differences (SMD)=-0.23, 95% CI=-0.37 to -0.1), systemic lupus erythematosus (SLE) (SMD=-0.54, 95% CI=-1.07 to -0.01) and spondyloarthritis (SMD=-0.94, 95% CI=-1.23 to -0.66); reduction of fatigue was not significant in Sjögren's syndrome (SMD=-0.83, 95% CI=-2.13 to 0.47) and systemic sclerosis (SMD=-0.66, 95% CI=-1.33 to 0.02). Psychoeducational interventions were efficacious in reducing fatigue in RA (SMD=-0.32, 95% CI=-0.48 to -0.16), but not in SLE (SMD=-0.19, 95% CI=-0.46 to 0.09). Follow-up models in consultations (SMD=-0.05, 95% CI=-0.29 to 0.20) and multicomponent interventions (SMD=-0.20, 95% CI=-0.53 to 0.14) did not show significant reductions of fatigue in RA. The results of RCTs not included in the meta-analysis suggest that several other non-pharmacological interventions may provide a reduction of fatigue, with reassuring safety results.
CONCLUSIONS
Physica activity or exercise and psychoeducational interventions are efficacious and safe for managing fatigue in people with I-RMDs.
Topics: Adult; Humans; Arthritis, Rheumatoid; Exercise; Lupus Erythematosus, Systemic; Musculoskeletal Diseases; Rheumatology
PubMed: 37604639
DOI: 10.1136/rmdopen-2023-003350 -
Journal of Autoimmunity Apr 2024Among the over 80 different autoimmune diseases, psoriasis (PsO), rheumatoid arthritis (RA), and ankylosing spondylitis (AS) are common representatives. Previous studies... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Among the over 80 different autoimmune diseases, psoriasis (PsO), rheumatoid arthritis (RA), and ankylosing spondylitis (AS) are common representatives. Previous studies indicated a potential link with cancer risk, but suffered often from low statistical power. Thus, we aimed to synthesize the evidence and quantify the association to different female-specific cancer sites.
METHODS
The systematic review was performed according to PRISMA guidelines. A search string was developed for the databases PubMed, Web of Science, Cochrane Library and Embase. Results were screened independently by two investigators and the risk of bias was assessed using the ROBINS-E tool. Meta-analyses were performed using inverse variance weighted random-effects models. Statistical between-study heterogeneity was quantified by calculating Cochran's Q, τ, and Higgins' I statistics. Sources of heterogeneity were analyzed and adjusted for within an intensive bias assessment in the form of meta-regression, outlier, influential, and subgroup analyses. A range of methods were used to test and adjust for publication bias.
RESULTS
Of 10,096 records that were originally identified by the search strategy, 45 were included in the meta-analyses. RA was inversely associated with both breast and uterine cancer occurrence, while PsO was associated with a higher breast cancer risk. Outlier-adjusted estimates confirmed these findings. Bias assessment revealed differences in geographic regions, particularly in RA patients, with higher estimates among Asian studies. An additional analysis revealed no association between psoriatic arthritis and breast cancer.
CONCLUSIONS
RA seems to reduce the risk of breast and uterine cancers, while PsO appears to increase breast cancer risk. Further large studies are required to investigate potential therapy-effects and detailed biological mechanisms.
Topics: Humans; Female; Autoimmune Diseases; Arthritis, Rheumatoid; Arthritis, Psoriatic; Psoriasis; Breast Neoplasms
PubMed: 38428110
DOI: 10.1016/j.jaut.2024.103187 -
Thyroid : Official Journal of the... Mar 2024Hashimoto thyroiditis (HT) is the most common cause of hypothyroidism in iodine-sufficient areas. Selenium is an essential trace element required for thyroid hormone... (Meta-Analysis)
Meta-Analysis
Hashimoto thyroiditis (HT) is the most common cause of hypothyroidism in iodine-sufficient areas. Selenium is an essential trace element required for thyroid hormone synthesis and exerts antioxidant effects. Therefore, it may be of relevance in the management of HT. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of selenium supplementation on thyroid function (thyrotropin [TSH], free and total thyroxine [fT4, T4], free and total triiodothyronine [fT3, T3]), thyroid antibodies (thyroid peroxidase antibodies [TPOAb], thyroglobulin antibodies [TGAb], thyrotropin receptor antibody [TRAb]), ultrasound findings (echogenicity, thyroid volume), immune markers, patient-reported outcomes, and adverse events in HT. The study protocol was registered on PROSPERO (CRD42022308377). We systematically searched MEDLINE, Embase, CINHAL, Web of Science, Google Scholar, and the Cochrane CENTRAL Register of Trials from inception to January 2023 and searched citations of eligible studies. Two independent authors reviewed and coded the identified literature. The primary outcome was TSH in patients without thyroid hormone replacement therapy (THRT); the others were considered secondary outcomes. We synthesized the results as standardized mean differences (SMD) or odds ratio (OR), assessed risk of bias using the Cochrane RoB 2 tool, and rated the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. We screened 687 records and included 35 unique studies. Our meta-analysis found that selenium supplementation decreased TSH in patients without THRT (SMD -0.21 [confidence interval, CI -0.43 to -0.02]; 7 cohorts, 869 participants; = 0%). In addition, TPOAb (SMD -0.96 [CI -1.36 to -0.56]; 29 cohorts; 2358 participants; = 90%) and malondialdehyde (MDA; SMD -1.16 [CI -2.29 to -0.02]; 3 cohorts; 248 participants; = 85%) decreased in patients with and without THRT. Adverse effects were comparable between the intervention and control groups (OR 0.89 [CI 0.46 to 1.75]; 16 cohorts; 1339 participants; = 0%). No significant changes were observed in fT4, T4, fT3, T3, TGAb, thyroid volume, interleukin (IL)-2, and IL-10. Overall, certainty of evidence was moderate. In people with HT without THRT, selenium was effective and safe in lowering TSH, TPOAb, and MDA levels. Indications for lowering TPOAb were found independent of THRT.
Topics: Humans; Autoantibodies; Dietary Supplements; Hashimoto Disease; Randomized Controlled Trials as Topic; Selenium; Thyrotropin
PubMed: 38243784
DOI: 10.1089/thy.2023.0556 -
Liver International : Official Journal... Nov 2023Patients with some chronic liver diseases have increased risk of diabetes. Whether this is also the case for patients with autoimmune liver diseases is unknown. The... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Patients with some chronic liver diseases have increased risk of diabetes. Whether this is also the case for patients with autoimmune liver diseases is unknown. The study aimed to calculate risk and worldwide prevalence of diabetes in patients with autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC).
METHODS
We performed a case-control study using data from the United Kingdom Biobank (UKB) and compared frequency of type 1 diabetes (T1D) and type 2 diabetes (T2D) in AIH and PBC with age-, sex-, BMI- and ethnicity-matched controls. Next, we performed a systematic review and proportional meta-analysis searching PubMed, Embase, Cochrane Library and Web of Science (inception to 1 May 2022 [AIH]; 20 August 2022 [PBC]; 11 November 2022 [PSC]). The pooled prevalence of diabetes was calculated using an inverse method random effects model.
RESULTS
Three hundred twenty-eight AIH patients and 345 PBC patients were identified in UKB and risk of T1D and T2D significantly increased compared with matched controls. Our systematic search identified 6914 records including the UKB study. Of these, 77 studies were eligible for inclusion comprising 36 467, 39 924 and 4877 individuals with AIH, PBC and PSC, respectively. The pooled prevalence of T1D was 3.8% (2.6%-5.7%), 1.7% (0.9%-3.1%), 3.1% (1.9%-4.8%) and of T2D 14.8% (11.1%-19.5%), 18.1% (14.6%-22.2%), 6.3% (2.8%-13.3%) in patients with AIH, PBC and PSC, respectively.
CONCLUSIONS
Patients with autoimmune liver diseases have increased risk of diabetes. Increased awareness of diabetes risk in patients with autoimmune liver diseases is warranted.
Topics: Humans; Liver Cirrhosis, Biliary; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Case-Control Studies; Propensity Score; Liver Diseases; Autoimmune Diseases; Hepatitis, Autoimmune; Cholangitis, Sclerosing
PubMed: 37752719
DOI: 10.1111/liv.15720 -
Annals of the Rheumatic Diseases Jan 2024To develop treat-to-target (T2T) recommendations in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR).
OBJECTIVES
To develop treat-to-target (T2T) recommendations in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR).
METHODS
A systematic literature review was conducted to retrieve data on treatment targets and outcomes in GCA/PMR as well as to identify the evidence for the effectiveness of a T2T-based management approach in these diseases. Based on evidence and expert opinion, the task force (29 participants from 10 countries consisting of physicians, a healthcare professional and a patient) developed recommendations, with consensus obtained through voting. The final level of agreement was provided anonymously.
RESULTS
Five overarching principles and six-specific recommendations were formulated. Management of GCA and PMR should be based on shared decisions between patient and physician recognising the need for urgent treatment of GCA to avoid ischaemic complications, and it should aim at maximising health-related quality of life in both diseases. The treatment targets are achievement and maintenance of remission, as well as prevention of tissue ischaemia and vascular damage. Comorbidities need to be considered when assessing disease activity and selecting treatment.
CONCLUSION
These are the first T2T recommendations for GCA and PMR. Treatment targets, as well as strategies to assess, achieve and maintain these targets have been defined. The research agenda highlights the gaps in evidence and the need for future research.
Topics: Humans; Giant Cell Arteritis; Polymyalgia Rheumatica; Quality of Life; Comorbidity
PubMed: 36828585
DOI: 10.1136/ard-2022-223429 -
Arthritis & Rheumatology (Hoboken, N.J.) Aug 2023To develop initial American College of Rheumatology (ACR) guidelines on the use of exercise, rehabilitation, diet, and additional interventions in conjunction with...
OBJECTIVE
To develop initial American College of Rheumatology (ACR) guidelines on the use of exercise, rehabilitation, diet, and additional interventions in conjunction with disease-modifying antirheumatic drugs (DMARDs) as part of an integrative management approach for people with rheumatoid arthritis (RA).
METHODS
An interprofessional guideline development group constructed clinically relevant Population, Intervention, Comparator, and Outcome (PICO) questions. A literature review team then completed a systematic literature review and applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate the certainty of evidence. An interprofessional Voting Panel (n = 20 participants) that included 3 individuals with RA achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations.
RESULTS
The Voting Panel achieved consensus on 28 recommendations for the use of integrative interventions in conjunction with DMARDs for the management of RA. Consistent engagement in exercise received a strong recommendation. Of 27 conditional recommendations, 4 pertained to exercise, 13 to rehabilitation, 3 to diet, and 7 to additional integrative interventions. These recommendations are specific to RA management, recognizing that other medical indications and general health benefits may exist for many of these interventions.
CONCLUSION
This guideline provides initial ACR recommendations on integrative interventions for the management of RA to accompany DMARD treatments. The broad range of interventions included in these recommendations illustrates the importance of an interprofessional, team-based approach to RA management. The conditional nature of most recommendations requires clinicians to engage persons with RA in shared decision-making when applying these recommendations.
Topics: Humans; United States; Rheumatology; Arthritis, Rheumatoid; Antirheumatic Agents; Diet; Exercise Therapy
PubMed: 37227071
DOI: 10.1002/art.42507 -
RMD Open Dec 2023Refractory autoimmune diseases remain a significant challenge in clinical practice and new therapeutic options are needed. This systematic review evaluates the existing...
OBJECTIVE
Refractory autoimmune diseases remain a significant challenge in clinical practice and new therapeutic options are needed. This systematic review evaluates the existing reported data on the CD38-targeting antibody daratumumab as a new therapeutic approach in autoantibody-mediated autoimmune diseases.
METHODS
A protocolised systematic literature review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed. Two databases (Medline and Embase) were searched for suitable studies. Usage of daratumumab in non-oncological or non-transplantation associated diseases with autoimmune pathophysiology was analysed including patient characteristics, therapeutic regimen, adverse events and patient outcome.
RESULTS
38 publications reporting the clinical course of 83 patients met the inclusion criteria. Daratumumab usage was reported in therapy-refractory cases (median of 5 different previous therapies) in 24 different autoimmune diseases. The median number of applications of daratumumab was 4, mainly via intravenous applications (87%). Concomitant treatment included glucocorticoids in 64% of patients, intravenous immunoglobulins (33%) and rituximab (17%). Remission or improvement of disease was reported in 81% of patients. Autoantibody depletion or reduction was stated in 52% of patients. Death occurred in three patients (3%). Adverse events were reported in 45% of patients including application-associated reaction (20%), infection (19%) and hypogammaglobulinaemia (33%).
CONCLUSION
Targeting CD38 via daratumumab is a new promising therapeutic option in therapy refractory autoimmune diseases. Efficacy as well as optimal therapeutic regimen and management or prevention of adverse events require further investigation. Therefore, systematic clinical trials of this therapeutic approach are needed.
Topics: Humans; Antibodies, Monoclonal; Rituximab; Autoimmune Diseases; Autoantibodies
PubMed: 38101819
DOI: 10.1136/rmdopen-2023-003604 -
International Journal of Dermatology Aug 2023Biologic agents (also termed biologics) have become an important adjuvant-targeted treatment option in autoimmune blistering disease. We evaluated the efficacy and... (Meta-Analysis)
Meta-Analysis Review
Biologic agents (also termed biologics) have become an important adjuvant-targeted treatment option in autoimmune blistering disease. We evaluated the efficacy and safety of newly licensed biologics for the management of pemphigoid using a meta-analysis. PubMed, EMBASE, Web of Science, and the Cochrane Library for studies involving pemphigoid patients treated with biological agents (rituximab, dupilumab, omalizumab, or mepolizumab) were searched. The pooled risk ratio (RR) with a 95% confidence interval (CI) was used to assess the short-term efficacy, adverse event (AE), relapse, and long-term survival. A total of seven studies involving 296 patients were identified. The pooled RRs for short-term effectiveness, AE, relapse, and long-term survival rate in patients treated with biological agents versus systemic corticosteroids were 1.37 (95% CI 0.95-1.97; I = 82%; P = 0.09), 0.54 (95% CI 0.39-0.73; I = 13%; P = 0.005), 1.36 (95% CI 0.95-1.96; I = 16.8%; P = 0.19), and 1.08 (95% CI 0.95-1.21; I = 48.1%; P = 0.53), respectively. Meta-regression and subgroup analysis revealed that the RRs of efficacy were 2.10 (95% CI 1.61-2.75; I = 0%; P < 0.00001) for rituximab and 2.07 (95% CI 1.61-2.67; I = 0%; P < 0.00001) for sample size greater than 30. Compared with conventional therapy, biologics treatment was significantly associated with fewer adverse events (P < 0.05), but no significant differences were found for efficacy and relapse (P > 0.05). The findings demonstrate that a biologics-containing regimen could minimize the occurrence of AEs and might display a comparable efficacy and recurrence to that of receiving systemic corticosteroids.
Topics: Humans; Rituximab; Biological Factors; Pemphigoid, Bullous; Adrenal Cortex Hormones; Chronic Disease; Biological Products; Recurrence
PubMed: 37212599
DOI: 10.1111/ijd.16678