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RMD Open Mar 2022Randomised controlled trials (RCTs) have compared biological and targeted systemic disease-modifying antirheumatic drugs (DMARDS) against placebo in psoriatic arthritis... (Meta-Analysis)
Meta-Analysis
Targeted systemic therapies for psoriatic arthritis: a systematic review and comparative synthesis of short-term articular, dermatological, enthesitis and dactylitis outcomes.
INTRODUCTION
Randomised controlled trials (RCTs) have compared biological and targeted systemic disease-modifying antirheumatic drugs (DMARDS) against placebo in psoriatic arthritis (PsA); few have compared them head to head.
OBJECTIVES
To compare the efficacy and safety of all evaluated DMARDs for active PsA, with a special focus on biological DMARDs (bDMARDs) licensed for PsA or psoriasis.
METHODS
A systematic review identified RCTs and Bayesian network meta-analysis (NMA) compared treatments on efficacy (American College of Rheumatology (ACR) response, Psoriasis Area and Severity Index (PASI) response, resolution of enthesitis and dactylitis) and safety (patients discontinuing due to adverse events (DAE)) outcomes. Subgroup analyses explored ACR response among patients with and without prior biological therapy exposure.
RESULTS
The NMA included 46 studies. Results indicate that some tumour necrosis factor inhibitors (anti-TNFs) may perform numerically, but not significantly, better than interleukin (IL) inhibitors on ACR response but perform worse on PASI response. Few significant differences between bDMARDs on ACR response were observed after subgrouping for prior bDMARD exposure. Guselkumab and IL-17A or IL-17RA inhibitors-brodalumab, ixekizumab, secukinumab-were best on PASI response. These IL-inhibitors and adalimumab were similarly efficacious on resolution of enthesitis and dactylitis. Infliximab with and without methotrexate, certolizumab 400 mg every 4 weeks and tildrakizumab showed the highest rates of DAE; abatacept, golimumab and the IL-inhibitors, the lowest.
CONCLUSIONS
Despite similar efficacy for ACR response, IL-17A and IL-17RA inhibitors and guselkumab offered preferential efficacy to anti-TNFs in skin manifestations, and for enthesitis and dactylitis, thereby supporting drug selection based on predominant clinical phenotype.
Topics: Abatacept; Antirheumatic Agents; Arthritis, Psoriatic; Enthesopathy; Humans
PubMed: 35321874
DOI: 10.1136/rmdopen-2021-002074 -
Frontiers in Immunology 2022We aim to evaluate the efficacy and tolerability of Janus kinase inhibitors (JAKi) as monotherapy and in combination with methotrexate (MTX) in active rheumatoid... (Meta-Analysis)
Meta-Analysis
Comparative efficacy and safety of JAK inhibitors as monotherapy and in combination with methotrexate in patients with active rheumatoid arthritis: A systematic review and meta-analysis.
BACKGROUND
We aim to evaluate the efficacy and tolerability of Janus kinase inhibitors (JAKi) as monotherapy and in combination with methotrexate (MTX) in active rheumatoid arthritis (RA).
METHODS
Medline, EMBASE, and Cochrane Library were systematically searched to identify relevant randomized controlled trials (RCTs). Pooled analysis was conducted using random-effects model, along with the risk difference (RD) and 95% confidence intervals (CIs).
RESULTS
Three RCTs, including 2,290 patients, were included. JAKi (tofacitinib, baricitinib, and filgotinib) plus MTX displayed a higher proportion of patients meeting the American College of Rheumatology (ACR) criteria than JAKi alone at week 52 (ACR20 RD 0.032; 95% CI -0.027 to 0.091; ACR50 RD 0.050; 95% CI 0.003 to 0.097; ACR70 RD 0.056; 95% CI 0.012 to 0.100). Similar results were observed for ACR20/50/70 at week 24. No significant difference was found between two regimens for the proportion of patients achieving Health Assessment Questionnaire disability index (HAQ-DI) improvement ≥ 0.22 at weeks 24 and 52. Regarding low disease activity and remission achievement, JAKi in combination with MTX, contributed higher response rates than JAKi alone at weeks 24 and 52. Compared with JAKi monotherapy, combination therapy had a higher risks of treatment-emergent adverse events (TEAEs) and adverse events (AEs) leading to study discontinuation.
CONCLUSION
JAKi combined with MTX demonstrated superiority to JAKi monotherapy in terms of ACR responses, low disease activity and remission achievement. The two regimens presented comparable physical functioning measured by HAQ-DI improvement and similar tolerability, except for high risks of TEAEs and AEs leading to study discontinuation in combination therapy.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021288907.
Topics: Humans; Antirheumatic Agents; Arthritis, Rheumatoid; Janus Kinase Inhibitors; Methotrexate
PubMed: 36248913
DOI: 10.3389/fimmu.2022.977265 -
Annals of the Rheumatic Diseases Jan 2023This systematic literature review (SLR) regarding the efficacy, duration of use and safety of glucocorticoids (GCs), was performed to inform the 2022 update of the EULAR... (Review)
Review
Efficacy, duration of use and safety of glucocorticoids: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis.
This systematic literature review (SLR) regarding the efficacy, duration of use and safety of glucocorticoids (GCs), was performed to inform the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis (RA). Studies on GC efficacy were identified from a separate search on the efficacy of disease-modifying antirheumatic drugs (DMARDs). A combined search was performed for the duration of use and safety of GCs in RA patients. Dose-defined and time-defined GC treatment of any dose and duration (excluding intra-articular GCs) prescribed in combination with other DMARDs were considered. Results are presented descriptively. Two included studies confirmed the efficacy of GC bridging as initial therapy, with equal efficacy after 2 years of initial doses of 30 mg/day compared with 60 mg/day prednisone. Based on a recently performed SLR, in clinical trials most patients starting initial GC bridging are able to stop GCs within 12 (22% patients continued on GCs) to 24 months (10% patients continued on GCs). The safety search included 12 RCTs and 21 observational studies. Well-known safety risks of GC use were confirmed, including an increased risk of osteoporotic fractures, serious infections, diabetes and mortality. Data on cardiovascular outcomes were Inconsistent. Overall, safety risks increased with increasing dose and/or duration, but evidence on which dose is safe was conflicting. In conclusion, this SLR has confirmed the efficacy of GCs in the treatment of RA. In clinical trials, most patients have shown to be able to stop GCs within 12-24 months. Well-known safety risks of GC use have been confirmed, but with heterogeneity between studies.
Topics: Humans; Glucocorticoids; Arthritis, Rheumatoid; Antirheumatic Agents; Prednisone; Drug Therapy, Combination
PubMed: 36410794
DOI: 10.1136/ard-2022-223358 -
JAMA Sep 2021Preeclampsia is a hypertensive disorder of pregnancy that poses serious maternal and infant health risks. Previous systematic reviews have established benefits of...
IMPORTANCE
Preeclampsia is a hypertensive disorder of pregnancy that poses serious maternal and infant health risks. Previous systematic reviews have established benefits of low-dose aspirin taken during pregnancy to prevent preeclampsia and its sequelae.
OBJECTIVE
To update evidence for the US Preventive Services Task Force (USPSTF) on effectiveness of aspirin use in preventing preeclampsia in individuals at increased risk based on clinical risk factors or measurements associated with higher disease incidence than in the general population.
DATA SOURCES
Studies from previous USPSTF review (2014), literature published January 2013 through May 15, 2020, in MEDLINE, PubMed (for publisher-supplied records only), EMBASE, and Cochrane Central Register of Controlled Trials. Ongoing surveillance through January 22, 2021.
STUDY SELECTION
Good- and fair-quality randomized clinical trials (RCTs) of low-dose aspirin use during pregnancy to prevent preeclampsia among individuals at increased risk; studies conducted in general populations to evaluate potential harms.
DATA EXTRACTION AND SYNTHESIS
Dual article screening and risk-of-bias assessment. Study data abstracted into prespecified forms, checked for accuracy. Random-effects meta-analysis.
MAIN OUTCOMES AND MEASURES
Diagnosis of preeclampsia; adverse pregnancy health outcomes and complications including eclampsia, perinatal mortality, preterm birth, small for gestational age, and potential bleeding harms or infant/child harms from aspirin exposure.
RESULTS
A total of 23 randomized clinical trials (RCTs) (N = 26 952) were included; 18 were conducted among participants at increased preeclampsia risk. Aspirin dosages ranged from 50 mg/d to 150 mg/d. Most trials enrolled majority White populations selected based on a range of risk factors. The incidence of preeclampsia among the trials of participants at increased risk ranged from 4% to 30%. Aspirin use was significantly associated with lower risk of preeclampsia (pooled relative risk [RR], 0.85 [95% CI, 0.75-0.95]; 16 RCTs [n = 14 093]; I2 = 0%), perinatal mortality (pooled RR, 0.79 [95% CI, 0.66-0.96]; 11 RCTs [n = 13 860]; I2 = 0%), preterm birth (pooled RR, 0.80 [95% CI, 0.67-0.95]; 13 RCTs [n = 13 619]; I2 = 49%), and intrauterine growth restriction (pooled RR, 0.82 [95% CI, 0.68-0.99]; 16 RCTs [n = 14 385]; I2 = 41%). There were no significant associations of aspirin use with risk of postpartum hemorrhage (pooled RR, 1.03 [95% CI, 0.94-1.12]; 9 RCTs [n = 23 133]; I2 = 0%) and other bleeding-related harms, or with rare perinatal or longer-term harms. Absolute risk reductions for preeclampsia associated with aspirin use ranged from -1% to -6% across larger trials (n >300) and were greater in smaller trials. For perinatal mortality, absolute risk reductions ranged from 0.5% to 1.1% in the 3 largest trials.
CONCLUSIONS AND RELEVANCE
Daily low-dose aspirin during pregnancy was associated with lower risks of serious perinatal outcomes for individuals at increased risk for preeclampsia, without evident harms.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Female; Humans; Infant, Newborn; Infant, Small for Gestational Age; Perinatal Death; Postpartum Hemorrhage; Practice Guidelines as Topic; Pre-Eclampsia; Pregnancy; Premature Birth; Randomized Controlled Trials as Topic; Risk Factors
PubMed: 34581730
DOI: 10.1001/jama.2021.8551 -
BMC Complementary Medicine and Therapies Jul 2020Osteoarthritis (OA) is the commonest form of inflammatory joint disease. Unfortunately, to date, there is no appropriate treatment for OA. Boswellia serrata was... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Osteoarthritis (OA) is the commonest form of inflammatory joint disease. Unfortunately, to date, there is no appropriate treatment for OA. Boswellia serrata was considered as a potent anti-inflammatory, anti-arthritic and analgesic agent that may be a drug for OA.
METHODS
In this meta-analysis, data from randomized controlled trials were obtained to assess the effects of Boswellia or its extract versus placebo or western medicine in patients with OA. The primary outcomes included visual analogue score (VAS), WOMAC pain, WOMAC stiffness, WOMAC function and lequesne index.
RESULT
Seven trials involving 545 patients were included. Compared with the control group, Boswellia and its extract may relieve the pain [VAS: (WMD -8.33; 95% CI -11.19, - 5.46; P<0.00001); WOMAC pain: (WMD -14.22; 95% CI -22.34, - 6.09; P = 0. 0006)] and stiffness [WOMAC stiffness: (WMD -10.04; 95% CI -15.86, - 4.22; P = 0. 0007)], and improve the joint's function [WOMAC function: (WMD -10.75; 95% CI -15.06, - 6.43; P<0. 00001); lequesne index: (WMD -2.27; 95% CI -3.08, - 1.45; P<0. 00001)].
CONCLUSION
Based on current evidence, Boswellia and its extract may be an effective and safe treatment option for patient with OA, and the recommended duration of treatment with Boswellia and its extract is at least 4 weeks.
Topics: Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Boswellia; Humans; Osteoarthritis, Knee; Pain Measurement; Plant Extracts; Randomized Controlled Trials as Topic; Surveys and Questionnaires; Triterpenes
PubMed: 32680575
DOI: 10.1186/s12906-020-02985-6 -
RMD Open Jan 2021To summarise, by a systematic literature review (SLR), the evidence regarding pharmacological and non-pharmacological therapeutic strategies in difficult-to-treat...
Pharmacological and non-pharmacological therapeutic strategies in difficult-to-treat rheumatoid arthritis: a systematic literature review informing the EULAR recommendations for the management of difficult-to-treat rheumatoid arthritis.
OBJECTIVES
To summarise, by a systematic literature review (SLR), the evidence regarding pharmacological and non-pharmacological therapeutic strategies in difficult-to-treat rheumatoid arthritis (D2T RA), informing the EULAR recommendations for the management of D2T RA.
METHODS
PubMed, Embase and Cochrane databases were searched up to December 2019. Relevant papers were selected and appraised.
RESULTS
Two hundred seven (207) papers studied therapeutic strategies. Limited evidence was found on effective and safe disease-modifying antirheumatic drugs (DMARDs) in patients with comorbidities and other contraindications that limit DMARD options (patients with obesity, hepatitis B and C, risk of venous thromboembolisms, pregnancy and lactation). In patients who previously failed biological (b-)DMARDs, all currently used b/targeted synthetic (ts-)DMARDs were found to be more effective than placebo. In patients who previously failed a tumour necrosis factor inhibitor (TNFi), there was a tendency of non-TNFi bDMARDs to be more effective than TNFis. Generally, effectiveness decreased in patients who previously failed a higher number of bDMARDs. Additionally, exercise, psychological, educational and self-management interventions were found to improve non-inflammatory complaints (mainly functional disability, pain, fatigue), education to improve goal setting, and self-management programmes, educational and psychological interventions to improve self-management.The identified evidence had several limitations: (1) no studies were found in patients with D2T RA specifically, (2) heterogeneous outcome criteria were used and (3) most studies had a moderate or high risk of bias.
CONCLUSIONS
This SLR underscores the scarcity of high-quality evidence on the pharmacological and non-pharmacological treatment of patients with D2T RA. Effectiveness of b/tsDMARDs decreased in RA patients who had failed a higher number of bDMARDs and a subsequent b/tsDMARD of a previously not targeted mechanism of action was somewhat more effective. Additionally, a beneficial effect of non-pharmacological interventions was found for improvement of non-inflammatory complaints, goal setting and self-management.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Biological Products; Drug Therapy, Combination; Female; Humans; Tumor Necrosis Factor-alpha
PubMed: 33419871
DOI: 10.1136/rmdopen-2020-001512 -
Annals of the Rheumatic Diseases Jan 2023Recent insights supporting the safety of live-attenuated vaccines and novel studies on the immunogenicity of vaccinations in the era of biological disease-modifying...
OBJECTIVES
Recent insights supporting the safety of live-attenuated vaccines and novel studies on the immunogenicity of vaccinations in the era of biological disease-modifying antirheumatic drugs in paediatric patients with autoimmune/inflammatory rheumatic diseases (pedAIIRD) necessitated updating the EULAR recommendations.
METHODS
Recommendations were developed using the EULAR standard operating procedures. Two international expert committees were formed to update the vaccination recommendations for both paediatric and adult patients with AIIRD. After a systematic literature review, separate recommendations were formulated for paediatric and adult patients. For pedAIIRD, six overarching principles and seven recommendations were formulated and provided with the level of evidence, strength of recommendation and Task Force level of agreement.
RESULTS
In general, the National Immunisation Programmes (NIP) should be followed and assessed yearly by the treating specialist. If possible, vaccinations should be administered prior to immunosuppressive drugs, but necessary treatment should never be postponed. Non-live vaccines can be safely given to immunosuppressed pedAIIRD patients. Mainly, seroprotection is preserved in patients receiving vaccinations on immunosuppression, except for high-dose glucocorticoids and B-cell depleting therapies. Live-attenuated vaccines should be avoided in immunosuppressed patients. However, it is safe to administer the measles-mumps-rubella booster and varicella zoster virus vaccine to immunosuppressed patients under specific conditions. In addition to the NIP, the non-live seasonal influenza vaccination should be strongly considered for immunosuppressed pedAIIRD patients.
CONCLUSIONS
These recommendations are intended for paediatricians, paediatric rheumatologists, national immunisation agencies, general practitioners, patients and national rheumatology societies to attain safe and effective vaccination and optimal infection prevention in immunocompromised pedAIIRD patients.
Topics: Adult; Humans; Child; Vaccines, Attenuated; Rheumatic Diseases; Vaccination; Immunosuppressive Agents; Antirheumatic Agents; Autoimmune Diseases
PubMed: 35725297
DOI: 10.1136/annrheumdis-2022-222574 -
Pharmacology 2022Janus kinase (JAK) inhibitors and secukinumab have been demonstrated to be effective treatments for ankylosing spondylitis (AS). However, there have been no head-to-head... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Janus kinase (JAK) inhibitors and secukinumab have been demonstrated to be effective treatments for ankylosing spondylitis (AS). However, there have been no head-to-head trials comparing the effectiveness and safety characteristics of JAK inhibitors with secukinumab. This study aimed to evaluate the relative effectiveness and safety of JAK inhibitors and secukinumab in patients with active AS.
SUMMARY
A Bayesian network meta-analysis was conducted using direct and indirect data from randomized controlled trials (RCTs) that examined the efficacy and safety of tofacitinib 5 mg, upadacitinib 15 mg, filgotinib 200 mg, and secukinumab 150 mg in patients with active AS who had a poor response or intolerance to nonsteroidal anti-inflammatory drugs (NSAIDs) and were tumor necrosis factor (TNF) inhibitor-naïve. Data from six RCTs comprising 937 patients were analyzed. The Assessment of SpondyloArthritis International Society 20 (ASAS20) response rates were significantly higher in the JAK inhibitors and secukinumab groups than in the placebo group. The surface under the cumulative ranking curve (SUCRA)-based ranking probability based on the ASAS20 response rate suggested that tofacitinib 5 mg had the highest likelihood of being the best treatment for achieving the ASAS20 response rate, followed by filgotinib 200 mg, upadacitinib 15 mg, secukinumab 150 mg, and placebo. The SUCRA-based ranking probability based on the ASAS20 response rate suggested that tofacitinib 5 mg had the highest likelihood of being the best treatment for achieving the ASAS40 response rate, followed by upadacitinib 15 mg, secukinumab 150 mg, filgotinib 200 mg, and placebo.
KEY MESSAGES
Tofacitinib 5 mg was the most effective treatment for AS, whereas JAK inhibitors and secukinumab 150 mg were effective treatments in patients with active AS who had a poor response or intolerance to NSAIDs and were TNF inhibitor-naïve.
Topics: Humans; Janus Kinase Inhibitors; Spondylitis, Ankylosing; Antirheumatic Agents; Treatment Outcome; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 35817017
DOI: 10.1159/000525627 -
The Journal of Arthroplasty Sep 2022To develop updated American College of Rheumatology/American Association of Hip and Knee Surgeons guidelines for the perioperative management of disease-modifying...
2022 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty.
OBJECTIVE
To develop updated American College of Rheumatology/American Association of Hip and Knee Surgeons guidelines for the perioperative management of disease-modifying medications for patients with rheumatic diseases, specifically those with inflammatory arthritis (IA) and those with systemic lupus erythematosus (SLE), undergoing elective total hip arthroplasty (THA) or elective total knee arthroplasty (TKA).
METHODS
We convened a panel of rheumatologists, orthopedic surgeons, and infectious disease specialists, updated the systematic literature review, and included currently available medications for the clinically relevant population, intervention, comparator, and outcomes (PICO) questions. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence and the strength of recommendations using a group consensus process.
RESULTS
This guideline updates the 2017 recommendations for perioperative use of disease-modifying antirheumatic therapy, including traditional disease-modifying antirheumatic drugs, biologic agents, targeted synthetic small-molecule drugs, and glucocorticoids used for adults with rheumatic diseases, specifically for the treatment of patients with IA, including rheumatoid arthritis and spondyloarthritis, those with juvenile idiopathic arthritis, or those with SLE who are undergoing elective THA or TKA. It updates recommendations regarding when to continue, when to withhold, and when to restart these medications and the optimal perioperative dosing of glucocorticoids.
CONCLUSION
This updated guideline includes recently introduced immunosuppressive medications to help decision-making by clinicians and patients regarding perioperative disease-modifying medication management for patients with IA and SLE at the time of elective THA or TKA.
Topics: Adult; Antirheumatic Agents; Arthritis, Rheumatoid; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Glucocorticoids; Humans; Lupus Erythematosus, Systemic; Rheumatic Diseases; Rheumatology; Surgeons; United States
PubMed: 35732511
DOI: 10.1016/j.arth.2022.05.043 -
Rheumatology (Oxford, England) May 2021The efficacy of the novel interleukin (IL)-23p19 inhibitor guselkumab for psoriatic arthritis (PsA) has recently been demonstrated in two phase 3 trials (DISCOVER-1 &... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The efficacy of the novel interleukin (IL)-23p19 inhibitor guselkumab for psoriatic arthritis (PsA) has recently been demonstrated in two phase 3 trials (DISCOVER-1 & -2) but has not been evaluated vs other targeted therapies for PsA. The objective was to compare guselkumab to targeted therapies for PsA for safety and joint and skin efficacy through network meta-analysis (NMA).
METHODS
A systematic literature review was conducted in January 2020 to identify randomized controlled trials. Bayesian NMAs were performed to compare treatments on American College of Rheumatology (ACR) 20/50/70 response, mean change from baseline in van der Heijde-Sharp (vdH-S) score, Psoriasis Area Severity Index (PASI) 75/90/100 response, adverse events (AEs) and serious adverse events (SAEs).
RESULTS
Twenty-six phase 3 studies evaluating 13 targeted therapies for PsA were included. For ACR 20 response, guselkumab 100 mg every 8 weeks (Q8W) was comparable to IL-17A inhibitors and subcutaneous tumor necrosis factor (TNF) inhibitors. Similar findings were observed for ACR 50 and 70. For vdH-S score, guselkumab Q8W was comparable to other agents except intravenous TNF therapies. Results for PASI 75 and PASI 90 response suggested guselkumab Q8W was better than most other agents. For PASI 100, guselkumab Q8W was comparable to other active agents. For AEs and SAEs, guselkumab Q8W ranked highly but comparative conclusions were uncertain. Similar results were observed for all outcomes for guselkumab 100 mg every four weeks.
CONCLUSIONS
In this NMA, guselkumab demonstrated favorable arthritis efficacy comparable to IL-17A and subcutaneous TNF inhibitors while offering better PASI response relative to many other treatments.
Topics: Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Psoriatic; Humans; Network Meta-Analysis; Treatment Outcome
PubMed: 33844022
DOI: 10.1093/rheumatology/keab119