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RMD Open Dec 2023To identify the best evidence on the efficacy of pharmacological interventions in reducing fatigue in people with inflammatory rheumatic and musculoskeletal diseases... (Meta-Analysis)
Meta-Analysis
Efficacy of 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 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 adults with I-RMDs conducted according to the Cochrane Handbook. Search strategy ran in Medline, Embase, Cochrane Library, CINAHL Complete, PEDro, OTseeker and PsycINFO. Only randomised controlled trials (RCTs) or controlled clinical trials were eligible. Assessment of risk of bias, data extraction and synthesis performed by two reviewers independently and in duplicate. Data pooled in statistical meta-analyses.
RESULTS
From 4151 records, 455 were selected for full-text review, 99 fulfilled the inclusion criteria and 19 RCTs were included in meta-analyses. Adalimumab was superior to placebo in reducing fatigue at 12 and 52 weeks in rheumatoid arthritis (RA) (n=3 and 2 RCTs; mean difference (MD)= -3.03, p<0.001; MD=-2.25, p=0.03, respectively). Golimumab (n=2 RCTs; 24 weeks: MD=-5.27, p<0.001), baricitinib (n=2 RCTs; 24 weeks: MD=-4.06, p<0.001), sarilumab (n=2 RCTs; 24 weeks: MD=-3.15, p<0.001), tocilizumab (n=3 RCTs; 24 weeks: MD=-3.69, p<0.001) and tofacitinib (n=3 RCTs; 12 weeks: MD=-4.44, p<0.001) were also superior to placebo in reducing fatigue in RA. A dose/effect relationship was observed for sarilumab, tocilizumab and tofacitinib. In spondyloarthritis (excluding psoriatic arthritis), secukinumab was superior to placebo in reducing fatigue at 16 weeks (n=2 RCTs; MD=-4.15, p<0.001), with a dose/effect relationship also observed. The narrative results of the RCTs not included in the meta-analysis indicated that several other pharmacological interventions were efficacious in reducing fatigue, with reassuring safety results.
CONCLUSIONS
Several pharmacological interventions are efficacious and generally safe for managing fatigue in people with I-RMDs.
Topics: Adult; Humans; Adalimumab; Arthritis, Rheumatoid; Fatigue
PubMed: 38056919
DOI: 10.1136/rmdopen-2023-003349 -
RMD Open Nov 2023Axial spondyloarthritis (axSpA) can limit work participation. Our objective was to characterise productivity in patients with axSpA, including changes after 12-16 weeks... (Meta-Analysis)
Meta-Analysis
Work productivity in patients with axial spondyloarthritis initiating biological or targeted synthetic disease-modifying antirheumatic drugs: a systematic literature review and meta-analysis.
BACKGROUND
Axial spondyloarthritis (axSpA) can limit work participation. Our objective was to characterise productivity in patients with axSpA, including changes after 12-16 weeks of treatment with biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs).
METHODS
A systematic literature review identified studies published from 1 January 2010 to 21 October 2021 reporting work productivity using the Work Productivity and Activity Impairment (WPAI) questionnaire in patients with axSpA initiating b/tsDMARDs. Baseline and Week 12-16 overall work productivity, absenteeism, presenteeism and activity impairment scores were used in a random-effects meta-analysis to calculate absolute mean change from baseline for each WPAI-domain.
RESULTS
Eleven studies in patients with axSpA who received either placebo (n=727) or treatment with adalimumab, bimekizumab, etanercept, ixekizumab, secukinumab or tofacitinib (n=994) were included. In working patients initiating a b/tsDMARD, mean baseline overall work productivity impairment, absenteeism and presenteeism scores were 52.1% (N=7 studies), 11.0% and 48.8% (N=6 studies), respectively. At Week 12-16, the pooled mean change from baseline in overall work impairment for b/tsDMARDs or placebo was -21.6% and -12.3%. When results were extrapolated to 1 year, the potential annual reductions in cost of paid and unpaid productivity loss per patient ranged from €11 962.88 to €14 293.54.
CONCLUSIONS
Over 50% of employed patients with active axSpA experienced work impairment, primarily due to presenteeism. Overall work productivity improved at Weeks 12-16 to a greater extent for patients who received b/tsDMARDs than placebo. Work productivity loss was associated with a substantial cost burden, which was reduced with improvements in impairment.
Topics: Humans; Antirheumatic Agents; Spondylitis, Ankylosing; Efficiency; Etanercept; Axial Spondyloarthritis
PubMed: 38035757
DOI: 10.1136/rmdopen-2023-003468 -
The Saudi Dental Journal Nov 2023This systematic review aims to investigate the impact of tumor necrotic factor alpha inhibitors in suppressing bone resorption in periodontitis, and its potential to... (Review)
Review
OBJECTIVES
This systematic review aims to investigate the impact of tumor necrotic factor alpha inhibitors in suppressing bone resorption in periodontitis, and its potential to cause osteonecrosis. Extensive electronic research was conducted following the PRISMA guidelines, which connected various aspects of anti-TNF-a (anti-tumor necrosis factor-a) to periodontitis and osteonecrosis patients.
BACKGROUND
TNF-a inhibitors are broadly indicated in the treatment of autoimmune patients with possible joint resorption and increased inflammatory processes such as rheumatoid arthritis and inflammatory bowel disease, where they reduce bone loss and certain mediators. As rheumatoid arthritis and periodontitis share many characteristics, these medications may also be helpful in the treatment of coexisting periodontitis. However, besides medical benefits, anti-TNF-a also exhibits several adverse effects, ranging from dizziness to tuberculosis. Osteonecrosis is considered a recent adverse impact.
METHODS
An extensive electronic systematic review following the PRISMA guidelines was performed for English-language papers using the following databases as sources of information: PubMed, Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Library Genesis, Worldwide Science, National Rheumatoid Arthritis Society (NRAS), and other related articles. This systematic review is registered on the PROSPERO platform under registration number CRD42022341753.
RESULTS
Twenty articles were identified after the exclusion criteria were applied. These include systematic reviews, case reports, retrospective cohort studies, case report series, -analyses, clinical trials, randomised clinical trials, cross-sectional and longitudinal analyses, longitudinal observational studies, and prospective clinical trials. All these were included in the quantitative and qualitative analyses.
CONCLUSIONS
Anti-TNF-a drugs show promising results in treating patients with rheumatoid arthritis and periodontitis but could be considered a risk factor for osteonecrosis. Hence, patients receiving such medications should be closely monitored by the dentist and physician before, during, and after administration.
PubMed: 38025596
DOI: 10.1016/j.sdentj.2023.07.006 -
Arquivos de Gastroenterologia 2023Fistulizing perianal Crohn's disease poses a treatment challenge, and researchers postulate that this phenotype in young male patients could have a worst outcome.
BACKGROUND
Fistulizing perianal Crohn's disease poses a treatment challenge, and researchers postulate that this phenotype in young male patients could have a worst outcome.
OBJECTIVE
Thus, the aim of this study was to assess whether sex influences the response to treatment for these patients.
METHODS
This systematic review (PROSPERO CRD42022319629) was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. We selected articles published in English, Spanish, Portuguese, and Italian between 2010 and 2020 in the PubMed and Science Direct databases. According to the PICO acronym, prospective studies in patients older than 18 years with the objective of treating fistulizing perianal Crohn's disease were selected. Studies in pediatric populations, retrospective, without treatment objectives, and that included only rectovaginal fistulas or a single sex were excluded. Study quality was assessed using the Cochrane risk of bias tool and Newcastle-Ottawa scale.
RESULTS
Of the 1887 articles found, 33 were included. Most studies used anti-TNF drugs as treatment (n=11). Ten studies had subgroup analyses; of them, the two studies reporting sex differences used infliximab and adalimumab as treatment and showed that women had a longer fistula closure time than men.
CONCLUSION
This systematic review showed that few data corroborate the difference between sexes in the treatment of fistulizing perianal Crohn's disease, possibly having a greater relationship with the phenotype. However, considering the lack of results, further studies with this objective and with standardization of fistulas and response assessment methods are needed.
Topics: Child; Humans; Male; Female; Crohn Disease; Retrospective Studies; Prospective Studies; Tumor Necrosis Factor Inhibitors; Rectal Fistula; Treatment Outcome; Infliximab
PubMed: 38018554
DOI: 10.1590/S0004-2803.230402023-28 -
Pharmaceuticals (Basel, Switzerland) Nov 2023Conventional therapy is the most commonly used treatment for Crohn's disease (CD), but it does not always achieve disease control, which is why the use of biologic drugs... (Review)
Review
Conventional therapy is the most commonly used treatment for Crohn's disease (CD), but it does not always achieve disease control, which is why the use of biologic drugs is increasing. The aim of this study was to analyze the efficacy and safety of biologic drugs in adult patients diagnosed with moderate-severe CD. An intensive search was performed in PubMed, Web of Science and Medline to collect phase 2 or 3 clinical trials published between 2018 and 2023 that were randomized, placebo-controlled and double-blind trials analyzing the efficacy and safety of biologic drugs in adult patients diagnosed with CD. This systematic review was conducted according to the PRISMA statement. Thirteen clinical trials evaluating eight biologic drugs were included. Upadacitinib, vedolizumab, adalimumab, guselkumab, mirikizumab, ustekinumab and risankizumab showed statistically significant efficacy across different clinical, endoscopic, histological, genetic, biomarker or quality-of-life parameters. However, PF-00547659 only showed statistically significant results for the CDAI-70 at week 12. In terms of safety, the incidence and severity of adverse effects were analyzed, with all drugs being well tolerated and presenting a good safety profile since most adverse effects were mild. Biologic drugs can be considered an effective and safe option for the treatment of moderate-severe CD in adult patients with an inadequate response or intolerance to conventional therapy.
PubMed: 38004446
DOI: 10.3390/ph16111581 -
PloS One 2023There are currently no studies comparing histologic remission of FDA-approved biologics for moderate to severe ulcerative colitis (UC), except for one head-to-head... (Meta-Analysis)
Meta-Analysis
BACKGROUNDS AND AIMS
There are currently no studies comparing histologic remission of FDA-approved biologics for moderate to severe ulcerative colitis (UC), except for one head-to-head VARSITY trial. The current study employs a network meta-analysis to compare the efficacy, including histologic remission and safety of biologic agents for UC.
METHODS
Using four electronic databases, including Pubmed, EMBASE, The Cochrane Library, and ClinicalTrials.gov, a search was conducted of all literature published until September 2022. Included were studies of randomized controlled trials with adult patients with moderate to severe UC using biologics approved by the FDA. An odd ratio with a 95 percent credible interval and ranking information was calculated for each endpoint.
RESULTS
The results of the network meta-analysis did not reveal statistically significant differences among biological agents. However, the ranking information for each biological agent exhibited the following patterns. Vedolizumab was ranked first for overall efficacy endpoints in the maintenance phase, including histologic remission. Except for histologic remission, Ustekinumab was identified as the top-ranked drug for induction phase efficacy endpoints other than histologic remission. Adalimumab was identified as the top-ranked drug for maintenance phase corticosteroid-free remission. Vedolizumab was identified as the top-ranked drug in the induction phase for Treatment Emergent Adverse Events (TEAE). Adalimumab was identified as the top-ranked drug in the induction phase for infection. For TEAE and infection in the maintenance phase and Treatment Emergent Severe Adverse Events (TESAE) in both the induction and maintenance phases, Ustekinumab was determined to be the top-ranked medication.
CONCLUSIONS
Including histologic remission, for the overall efficacy endpoints in the maintenance phase, VDZ was identified as the first rank drug, but there was no statistically significant difference between biologics. Therefore, the generalization of the results of this study is bounded due to the intrinsic limitations of the study provided.
Topics: Adult; Humans; Colitis, Ulcerative; Adalimumab; Ustekinumab; Network Meta-Analysis; Biological Factors; Biological Products; Biological Therapy
PubMed: 37917756
DOI: 10.1371/journal.pone.0293655 -
Expert Review of Clinical Immunology 2023Palmoplantar psoriasis (PP) represents a localized type of disease. While controversy over its' classification exists, a hyperkeratotic type, a pustular type and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Palmoplantar psoriasis (PP) represents a localized type of disease. While controversy over its' classification exists, a hyperkeratotic type, a pustular type and palmoplantar pustulosis (PPP) have been recognized. PP management is regularly supported by biologic agents. Our study aimed to review and synthesize available data regarding the efficacy of approved biologics for PP and PPP.
RESEARCH DESIGN AND METHODS
A literature search was conducted in PubMed, CENTRAL, Scopus, and ClinicalTrilas.gov. Utilizing random-effects inverse-variance frequentist network meta-analyses (NMAs), we ranked interventions. The proportion of participants with cleared skin was the primary outcome. Fifty and 75% improvement in palmoplantar psoriasis area severity index (PPASI) were also explored (PPASI50, PPASI75).
RESULTS
In total, 15 randomized controlled trials (RCTs) exploring the efficacy of on-label adalimumab, bimekizumab, etanercept, guselkumab, infliximab, ixekizumab, secukinumab, and ustekinumab were included. Data for PP were synthesized. Every biologic agent examined, except from infliximab, outperformed placebo. On-label secukinumab exhibited the highest probability of inducing complete resolution. Ixekizumab and infliximab ranked best on inducing PPASI50 and PPASI75. Our review supports that guselkumab is effective for PPP.
CONCLUSIONS
Secukinumab, ixekizumab and infliximab are effective for PP. Research is warranted to produce evidence about the efficacy of biologics in PP and PPP.
Topics: Humans; Infliximab; Network Meta-Analysis; Biological Factors; Psoriasis; Biological Products; Severity of Illness Index; Treatment Outcome
PubMed: 37842734
DOI: 10.1080/1744666X.2023.2272049 -
Cureus Sep 2023The widely accepted standard of care for chronic cutaneous sarcoidosis is corticosteroids. However, when this treatment is shown to be refractory, other interventions... (Review)
Review
Recent Clinical Studies on the Effects of Tumor Necrosis Factor-Alpha (TNF-α) and Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) Antibody Therapies in Refractory Cutaneous Sarcoidosis: A Systematic Review.
The widely accepted standard of care for chronic cutaneous sarcoidosis is corticosteroids. However, when this treatment is shown to be refractory, other interventions must be considered. In this review, we report the current progress of clinical studies on various monoclonal antibody therapies and their future potential as primary interventions for refractory cutaneous sarcoidosis. In this systematic review, clinical studies on the management of refractory cutaneous sarcoidosis were retrieved from PubMed and ScienceDirect databases. Studies were screened based on article type, publication within the last 10 years, and access to free full text. The articles selected consisted of case studies, clinical trials, and observational studies. The studies needed to focus on cases of diagnosed cutaneous sarcoidosis at the time of the study and involve adult patients resistant to corticosteroid regimens, with or without additional immunomodulators. Only interventions that included tumor necrosis factor-alpha (TNF-α) (e.g., infliximab and adalimumab) or Janus kinase/signal transducers and activators of transcription (JAK/STAT) (e.g., ruxolitinib and tofacitinib) antibody therapy were considered. Two authors independently conducted quality assessments using the Joanna Briggs Institute Critical Appraisal and NIH Study Quality Assessment tools. A total of 16 clinical studies were included in this systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram. Of the 16 cases included, 15 studies demonstrated partial to complete resolution of cutaneous lesions within a range of two weeks to 18 months from initiation of antibody therapy. Studies on anti-TNF-α intervention demonstrated the most adverse events, including two deaths and one case associated with cutaneous exacerbation. Studies on anti-JAK-STAT interventions demonstrate no adverse events after treatment; however, patient study size was limiting. Recent studies have shown promising potential for anti-TNF-α and anti-JAK-STAT inhibitors to become the mainstay interventions in refractory cutaneous sarcoidosis. Due to limited population studies, the current data on the efficacy and safety of antibody therapies have not yielded a standardized FDA-approved steroid-sparing treatment. Therefore, a need for more population studies on the effectiveness of third-line intervention in refractory cutaneous sarcoidosis is necessary.
PubMed: 37818515
DOI: 10.7759/cureus.44901 -
Journal of Gastrointestinal Surgery :... Nov 2023This systematic review explored different medications and methods for prevention and treatment of pouchitis after restorative proctocolectomy with ileal pouch-anal... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This systematic review explored different medications and methods for prevention and treatment of pouchitis after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA).
METHODS
PubMed, Scopus, and Web of Science were searched for randomized clinical trials that assessed prevention or treatment of pouchitis. The systematic review was reported in line with updated 2020 PRISMA guidelines. Risk of bias in the trials included was assessed using the ROB-2 tool and certainty of evidence was assessed using GRADE. The main outcomes were the incidence of new pouchitis episodes in the preventative studies and resolution or improvement of active pouchitis in the treatment studies.
RESULTS
Fifteen randomized trials were included. A meta-analysis of 7 trials on probiotics revealed significantly lower odds of pouchitis with the use of probiotics (RR: 0.26, 95% CI: 0.16-0.42, I = 20%, p < 0.001) and similar odds of adverse effects to placebo (RR: 2.43, 95% CI: 0.11-55.9, I = 0, p = 0.579). One trial investigated the prophylactic role of allopurinol in preventing pouchitis and found a comparable incidence of pouchitis in the two groups (31% vs 28%; p = 0.73). Seven trials assessed different treatments for active pouchitis. One recorded the resolution of pouchitis in all patients treated with ciprofloxacin versus 67% treated with metronidazole. Both budesonide enema and oral metronidazole were associated with similar significant improvement in pouchitis (58.3% vs 50%, p = 0.67). Rifaximin, adalimumab, fecal microbiota transplantation, and bismuth carbomer foam enema were not effective in treating pouchitis.
CONCLUSIONS
Probiotics are effective in preventing pouchitis after IPAA. Antibiotics, including ciprofloxacin and metronidazole, are likely effective in treating active pouchitis.
Topics: Humans; Pouchitis; Metronidazole; Colitis, Ulcerative; Randomized Controlled Trials as Topic; Proctocolectomy, Restorative; Ciprofloxacin; Anastomosis, Surgical
PubMed: 37815701
DOI: 10.1007/s11605-023-05841-3 -
Clinical and Experimental Rheumatology Jan 2024The approval of TNF-a inhibitors (TNFi) was a breakthrough in the treatment of ankylosing spondylitis (AS). Although also effective in psoriasis, drug-related adverse... (Review)
Review
OBJECTIVES
The approval of TNF-a inhibitors (TNFi) was a breakthrough in the treatment of ankylosing spondylitis (AS). Although also effective in psoriasis, drug-related adverse events of onset of psoriasiform skin lesions - paradoxical psoriasis (PP) under TNFi have been reported.
METHODS
We performed an electronic data search in MEDLINE via Pubmed and Cochrane library scientific databases from inception to January 2023, following the PRISMA guidelines. We assessed the distinct characteristics and frequency of risks for PP appearance in AS patients treated with different TNFi.
RESULTS
PP was found in 0.5-1% of TNFi-treated AS patients and the latency period was 2-11 months. The safest TNFi in terms of PP induction was certolizumab, whereas the one most commonly associated with PP was infliximab.
CONCLUSIONS
PP is an uncommon adverse reaction to TNFi treatment in AS patients and responds well to drug withdrawal. More large data studies need to be conducted though, to shed light on PP nature and management.
Topics: Humans; Spondylitis, Ankylosing; Tumor Necrosis Factor-alpha; Tumor Necrosis Factor Inhibitors; Infliximab; Psoriasis; Adalimumab
PubMed: 37812484
DOI: 10.55563/clinexprheumatol/rq4k3u