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Clinical Rheumatology Dec 2015Dermatomyositis and polymyositis are rare chronic inflammatory disorders with significant associated morbidity and mortality despite treatment. High-dose corticosteroids... (Review)
Review
Dermatomyositis and polymyositis are rare chronic inflammatory disorders with significant associated morbidity and mortality despite treatment. High-dose corticosteroids in addition to other interventions such as immunosuppressants, immunomodulators, and more recently, biologics are commonly used in clinical practice; however, there are no clear guidelines directing their use. Our objective was to systematically review the evidence for immunotherapy in the treatment of dermatomyositis and polymyositis. Relevant studies were identified through Embase and PubMed database searches. Trials were selected using pre-determined selection criteria and then assessed for quality. Randomized controlled trials and experimental studies without true randomization and including adult patients with definite or probable dermatomyositis or polymyositis were evaluated. Any type of immunotherapy was considered. Clinical improvement, judged by assessment of muscle strength after 6 months, was the primary outcome. Secondary outcomes included IMACS definition of improvement, improvements in patient and physician global scores, physical function, and muscle enzymes. Twelve studies met eligibility criteria. Differences in trial design, quality, and variable reporting of baseline characteristics and outcomes made direct comparison impossible. Although no treatment can be recommended on the basis of this review, improved outcomes were demonstrated with a number of agents including methotrexate, azathioprine, ciclosporin, rituximab, and intravenous immunoglobulin. Plasmapheresis and leukapheresis were of no apparent benefit. More high-quality randomized controlled trials are needed to establish the role of immunosuppressive agents in the treatment of these conditions and the clinical context in which they are most likely to be beneficial.
Topics: Adrenal Cortex Hormones; Azathioprine; Biological Products; Cyclosporine; Dermatomyositis; Evidence-Based Medicine; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Immunosuppressive Agents; Leukapheresis; Methotrexate; Plasmapheresis; Polymyositis; Practice Guidelines as Topic; Rituximab; Treatment Outcome
PubMed: 26299472
DOI: 10.1007/s10067-015-3059-y -
Rheumatology International Jul 2017The aim is to systematically review the treatment for lupus nephritis (LN) by performing an overview of systematic reviews and meta-analyses. Electronic databases of... (Review)
Review
The aim is to systematically review the treatment for lupus nephritis (LN) by performing an overview of systematic reviews and meta-analyses. Electronic databases of OVID MEDLINE, OVID EMBASE, and Cochrane Library were searched to identify published systematic reviews and meta-analyses investigating treatments for LN up to 13 July 2016. A measurement tool to assess systematic reviews (AMSTAR) was used to assess the quality of included studies. Totally, 24 studies were included. Of the eligible studies, 3 studies were rated as poor quality, 11 as moderate, and 10 as good. In LN induction therapy, comparing to cyclophosphamide, tacrolimus had higher complete remission rate, response rate, and anti-dsDNA negative conversion rate and led to lower risks of gastrointestinal symptoms and amenorrhea, and mycophenolate mofetil (MMF) was associated with higher response rate and less adverse events of leucopenia, alopecia, and ovarian failure. However, there was no difference in the efficacy and adverse events between tacrolimus and MMF. In LN maintenance therapy, the relapse rate and leucopenia rate were lower in MMF group than in azathioprine group, but there were no differences of end-stage kidney disease rate and mortality rate between the two groups. For LN induction therapy, both Tacrolimus and MMF are more effective and safer than cyclophosphamide, while there are no differences of efficacy or safety between the two treatments. For LN maintenance therapy, MMF seems to have less adverse events and lower relapse rate than azathioprine.
Topics: Disease Progression; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Lupus Nephritis; Meta-Analysis as Topic; Odds Ratio; Recurrence; Remission Induction; Risk Factors; Treatment Outcome
PubMed: 28493175
DOI: 10.1007/s00296-017-3733-2 -
Contact Dermatitis Nov 2023Parthenium dermatitis is the commonest form of plant dermatitis in India, caused by the plant Parthenium hysterophorus. Systemic immunosuppressives are commonly employed... (Meta-Analysis)
Meta-Analysis Review
Parthenium dermatitis is the commonest form of plant dermatitis in India, caused by the plant Parthenium hysterophorus. Systemic immunosuppressives are commonly employed in its treatment. However, there is a relative lack of comparative head-to-head trials. This study was done to assess the relative efficacy and safety of systemic treatments in Parthenium dermatitis. We systematically reviewed all the published studies investigating the safety and efficacy of systemic treatments for Parthenium dermatitis in the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and clinical trial registries. Treatment benefit data were tabulated based on outcome measures of scoring systems. The quality of evidence for each outcome was assessed by Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria for meta-analysis. The pooled Standardized mean difference (SMD) for case series and comparative studies based on clinical severity score (CSS) for azathioprine was 4.007 (95% CI (Confidence interval): 3.141, 4.873) and 0.746 (95% CI: 0.139, 1.352), respectively. About 88.8% (95% CI: 76.8%, 100.8%, p = 0.076) of the patients had excellent or a good response to azathioprine. Our meta-analysis shows that azathioprine has the highest level of evidence in the treatment of Parthenium dermatitis.
Topics: Humans; Azathioprine; Dermatitis, Allergic Contact; Immunosuppressive Agents; Asteraceae; India
PubMed: 37634936
DOI: 10.1111/cod.14406 -
Drug Safety Apr 2024Progressive multifocal leukoencephalopathy (PML) was first described among patients affected by hematological or solid tumors. Following the human immunodeficiency virus... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Progressive multifocal leukoencephalopathy (PML) was first described among patients affected by hematological or solid tumors. Following the human immunodeficiency virus (HIV) epidemic, people living with HIV have represented most cases for more than a decade. With the diffusion of highly active antiretroviral therapy, this group progressively decreased in favor of patients undergoing treatment with targeted therapy/immunomodulators. In this systematic review and meta-analysis, the objective was to assess which drugs are most frequently related to PML development, and report the incidence of drug-induced PML through a meta-analytic approach.
METHODS
The electronic databases MEDLINE, EMBASE, ClinicalTrials.gov, Web of Science and the Canadian Agency for Drugs and Technologies in Health Database (CADTH) were searched up to May 10, 2022. Articles that reported the risk of PML development after treatment with immunomodulatory drugs, including patients of both sexes under the age of 80 years, affected by any pathology except HIV, primary immunodeficiencies or malignancies, were included in the review. The incidence of drug-induced PML was calculated based on PML cases and total number of patients observed per 100 persons and the observation time. Random-effect metanalyses were conducted for each drug reporting pooled incidence with 95% confidence intervals (CI) and median (interquartile range [IQR]) of the observation time. Heterogeneity was measured by I statistics. Publication bias was examined through funnel plots and Egger's test.
RESULTS
A total of 103 studies were included in the systematic review. In our analysis, we found no includible study reporting cases of PML during the course of treatment with ocrelizumab, vedolizumab, abrilumab, ontamalimab, teriflunomide, daclizumab, inebilizumab, basiliximab, tacrolimus, belimumab, infliximab, firategrast, disulone, azathioprine or danazole. Dalfampridine, glatiramer acetate, dimethyl fumarate and fingolimod show a relatively safe profile, although some cases of PML have been reported. The meta-analysis showed an incidence of PML cases among patients undergoing rituximab treatment for multiple sclerosis (MS) of 0.01 cases/100 persons (95% CI - 0.08 to 0.09; I = 20.4%; p = 0.25) for a median observation period of 23.5 months (IQR 22.1-42.1). Treatment of MS with natalizumab carried a PML risk of 0.33 cases/100 persons (95% CI 0.29-0.37; I = 50%; p = 0.003) for a median observation period of 44.1 months (IQR 28.4-60) and a mean number of doses of 36.3 (standard deviation [SD] ± 20.7). When comparing data about patients treated with standard interval dosing (SID) and extended interval dosing (EID), the latter appears to carry a smaller risk of PML, that is, 0.08 cases/100 persons (95% CI 0.0-0.15) for EID versus 0.3 cases/100 persons (95% CI 0.25-0.34) for SID.
CONCLUSIONS
A higher risk of drug-related PML in patients whose immune system is not additionally depressed by means of neoplasms, HIV or concomitant medications is found in the neurological field. This risk is higher in MS treatment, and specifically during long-term natalizumab therapy. While this drug is still routinely prescribed in this field, considering the efficacy in reducing MS relapses, in other areas it could play a smaller role, and be gradually replaced by other safer and more recently approved agents.
Topics: Male; Female; Humans; Aged, 80 and over; Natalizumab; Leukoencephalopathy, Progressive Multifocal; Canada; Immunologic Factors; Multiple Sclerosis; HIV Infections
PubMed: 38321317
DOI: 10.1007/s40264-023-01383-4 -
Alimentary Pharmacology & Therapeutics Nov 2013Thiopurines maintain remission and modify disease course in inflammatory bowel disease. Use is limited by intolerance and subsequent drug withdrawal in approximately 17%... (Meta-Analysis)
Meta-Analysis Observational Study Review
A trial of mercaptopurine is a safe strategy in patients with inflammatory bowel disease intolerant to azathioprine: an observational study, systematic review and meta-analysis.
BACKGROUND
Thiopurines maintain remission and modify disease course in inflammatory bowel disease. Use is limited by intolerance and subsequent drug withdrawal in approximately 17% of patients treated with azathioprine. Previous case series have addressed the success rates of re-treatment with mercaptopurine in these individuals.
AIMS
To determine the rate of tolerance when trialling mercaptopurine in azathioprine-intolerant patients and the factors predictive of success, and to perform a systematic review and meta-analysis of these data with other published data sets.
METHODS
A retrospective observational study of 149 patients with IBD (82 with Crohn's disease and 67 with ulcerative colitis) previously intolerant of azathioprine subsequently treated with mercaptopurine was performed. A meta-analysis was undertaken of all published studies of mercaptopurine use in azathioprine-intolerant patients (455 patients in 11 included studies).
RESULTS
Mercaptopurine was tolerated by 58% of azathioprine-intolerant patients in the Edinburgh cohort. In the meta-analysis, 68% tolerated mercaptopurine. A higher proportion of those in the meta-analysis with GI toxicity (62%) or hepatotoxicity (81%) were able to tolerate mercaptopurine than those with flu-like illness (36%). Among those patients who ceased mercaptopurine for further adverse effects, 59% experienced the same adverse effect as they had with azathioprine.
CONCLUSIONS
This meta-analysis shows that switching to mercaptopurine is a safe therapeutic strategy for over two-thirds of azathioprine-intolerant patients and may help optimise immunomodulatory therapy in inflammatory bowel disease. A trial of mercaptopurine should be attempted in IBD patients (except those with acute pancreatitis or bone marrow aplasia) before considering thiopurine intolerance.
Topics: Adult; Azathioprine; Colitis, Ulcerative; Crohn Disease; Female; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Male; Mercaptopurine; Middle Aged; Retrospective Studies
PubMed: 24117596
DOI: 10.1111/apt.12511 -
The Journal of Rheumatology Oct 2016To compare benefits and harms of lupus nephritis (LN) induction and maintenance treatments. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To compare benefits and harms of lupus nephritis (LN) induction and maintenance treatments.
METHODS
We performed a systematic review and Bayesian network metaanalyses of randomized controlled trials (RCT) of immunosuppressive drugs or corticosteroids (CS) in LN. OR and 95% credible intervals (CrI) were calculated.
RESULTS
There were 65 RCT that met inclusion and exclusion criteria. Significantly lower risk of endstage renal disease (ESRD; 17 studies) was seen with cyclophosphamide (CYC; OR 0.49, 95% CrI 0.25-0.92) or CYC + azathioprine (AZA; OR 0.18, 95% CrI 0.05-0.57) compared with standard-dose CS, and with high-dose (HD) CYC (OR 0.16, 95% CrI 0.03-0.61) or CYC + AZA (OR 0.10, 95% CrI 0.03-0.34) compared with HD CS. HD CS was associated with higher risk of ESRD compared with CYC (OR 3.59, 95% CrI 1.30-9.86), AZA (OR 2.93, 95% CrI 1.08-8.10), or mycophenolate mofetil (MMF; OR 7.05, 95% CrI 1.66-31.91). Compared with CS, a significantly higher proportion of patients had renal response (14 studies) when treated with CYC (OR 1.98, 95% CrI 1.13-3.52), MMF (OR 2.42, 95% CrI 1.27-4.74), or tacrolimus (TAC; OR 4.20, 95% CrI 1.29-13.68). No differences were noted for the risk of malignancy (15 studies). The risk of herpes zoster (17 studies) was as follows: OR (95% CrI) MMF versus CS 4.38 (1.02-23.87), CYC versus CS 6.64 (1.97-25.71), TAC versus CS 9.11 (1.13-70.99), and CYC + AZA versus CS 8.46 (1.99-43.61).
CONCLUSION
Renal benefits and the risk of herpes zoster were higher for immunosuppressive drugs versus CS. Data on relative and absolute differences are now available, which can be incorporated into patient-physician discussions related to systemic lupus erythematosus medication use.
Topics: Adrenal Cortex Hormones; Cyclophosphamide; Humans; Immunosuppressive Agents; Lupus Nephritis; Remission Induction; Tacrolimus; Treatment Outcome
PubMed: 27585688
DOI: 10.3899/jrheum.160041 -
Journal of Gastroenterology Oct 2021The effectiveness of azathioprine (AZA) in preventing relapse and maintaining autoimmune pancreatitis (AIP) remission has been reported; however, most of these studies... (Meta-Analysis)
Meta-Analysis Review
The effectiveness of azathioprine (AZA) in preventing relapse and maintaining autoimmune pancreatitis (AIP) remission has been reported; however, most of these studies are case series with no randomized control trials available in the literature. Therefore, this study performed a systematic review and meta-analysis of the existing literature on this subject to determine the clinical efficacy of AZA as maintenance therapy for AIP patients. A systematic search was performed to identify studies on the clinical efficacy of AZA as maintenance therapy in AIP patients. The crude multiple relapse rate was estimated to assess the ability of AZA to control relapses in AIP. Pooled estimates were obtained using a random-effects model with the DerSimonian-Laird method. We identified AIP patients who did not respond to initial steroid treatment, experienced steroid weaning failure, or those who relapsed during remission as refractory cases. After reviewing the studies, ten articles fulfilled the inclusion criteria and were selected for meta-analysis. Of all 4504 patients, 3534 patients were treated with steroids, and 346 patients were treated with AZA for relapsed AIP. In this meta-analysis, 14/73 (19.2%) patients receiving AZA for refractory AIP relapsed. Meanwhile, 14/47 (29.8%) patients without AZA experienced relapse. The integrated odds ratio for relapse risk in patients receiving AZA was estimated to be 0.52 (p = 0.15). This systematic review and meta-analysis demonstrated the efficacy of AZA in preventing relapse of AIP, which supports the use of AZA as a maintenance treatment in patients with AIP who relapse upon withdrawal of steroid therapy.
Topics: Humans; Autoimmune Pancreatitis; Azathioprine; Immunosuppressive Agents; Remission Induction; Treatment Outcome
PubMed: 34426870
DOI: 10.1007/s00535-021-01817-9 -
Journal of the American Academy of... Aug 2015The assumption that adjuvant modalities have added value to oral glucocorticoids in the treatment of pemphigus is intuitively sound but has not been conclusively proven. (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
The assumption that adjuvant modalities have added value to oral glucocorticoids in the treatment of pemphigus is intuitively sound but has not been conclusively proven.
OBJECTIVE
We sought to compare the efficacy and safety of oral glucocorticoid treatment with or without adjuvants for pemphigus vulgaris and pemphigus foliaceus.
METHODS
We performed a systematic review and meta-analysis of randomized controlled trials. The primary outcome was remission. Secondary outcomes were disease control, time to disease control, relapse, time to relapse, cumulative glucocorticoid dose, withdrawal because of adverse events, and all-cause death. Trials were pooled irrespective of adjuvant type evaluated.
RESULTS
Ten trials (559 participants) were included. Adjuvants evaluated were azathioprine, mycophenolate mofetil, cyclophosphamide, cyclosporine, intravenous immunoglobulin, plasma exchange, and infliximab; not all were included in every analysis. Although adjuvants were not beneficial for achieving remission, they were found to collectively decrease the risk of relapse by 29% (relative risk 0.71, 95% confidence interval 0.53-0.95).
LIMITATIONS
Different adjuvants were pooled together.
CONCLUSION
Adjuvants have a role in pemphigus treatment, at least in reducing the risk of relapse. Further randomized controlled trials of other promising modalities are warranted.
Topics: Antineoplastic Agents; Drug Therapy, Combination; Female; Follow-Up Studies; Glucocorticoids; Humans; Immunosuppressive Agents; Male; Pemphigus; Randomized Controlled Trials as Topic; Recurrence; Remission Induction; Risk Assessment; Role; Severity of Illness Index; Treatment Outcome
PubMed: 26088689
DOI: 10.1016/j.jaad.2015.04.038 -
Systematic Reviews Sep 2016There is a lack of high-quality meta-analyses and network meta-analyses of immunosuppressive drugs for lupus nephritis. Our objective was to assess the comparative... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
There is a lack of high-quality meta-analyses and network meta-analyses of immunosuppressive drugs for lupus nephritis. Our objective was to assess the comparative benefits and harms of immunosuppressive drugs and corticosteroids in lupus nephritis.
METHODS
We conducted a systematic review and network meta-analysis (NMA) of trials of immunosuppressive drugs and corticosteroids in patients with lupus nephritis. We calculated odds ratios (OR) and 95 % credible intervals (CrI).
RESULTS
Sixty-five studies that met inclusion and exclusion criteria; data were analyzed for renal remission/response (37 trials; 2697 patients), renal relapse/flare (13 studies; 1108 patients), amenorrhea/ovarian failure (eight trials; 839 patients) and cytopenia (16 trials; 2257 patients). Cyclophosphamide [CYC] low dose (LD) and CYC high-dose (HD) were less likely than mycophenolate mofetil [MMF] and azathioprine [AZA], CYC LD, CYC HD and plasmapharesis less likely than cyclosporine [CSA] to achieve renal remission/response. Tacrolimus [TAC] was more likely than CYC LD to achieve renal remission/response. MMF and CYC were associated with a lower odds of renal relapse/flare compared to PRED and MMF was associated with a lower rate of renal relapse/flare than AZA. CYC was more likely than MMF and PRED to be associated with amenorrhea/ovarian failure. Compared to MMF, CYC, AZA, CYC LD, and CYC HD were associated with a higher risk of cytopenia.
CONCLUSIONS
In this systematic review and NMA, we found important differences between immunosuppressives used for the treatment of lupus nephritis. Patients and physicians can use this information for detailed informed consent in a patient-centered approach. Study limitations of between-study clinical heterogeneity and small sample size with type II error must be considered when interpreting these findings.
PROSPERO
CRD42016032965.
Topics: Adrenal Cortex Hormones; Clinical Trials as Topic; Drug Therapy, Combination; Glucocorticoids; Humans; Immunosuppressive Agents; Lupus Nephritis; Network Meta-Analysis; Odds Ratio; Treatment Outcome
PubMed: 27619512
DOI: 10.1186/s13643-016-0328-z -
BMJ Clinical Evidence Aug 2007Rheumatoid arthritis usually starts as a symmetrical polyarthritis, and its course is marked by flares and remissions. The aims of treatment are to relieve pain and... (Review)
Review
INTRODUCTION
Rheumatoid arthritis usually starts as a symmetrical polyarthritis, and its course is marked by flares and remissions. The aims of treatment are to relieve pain and swelling, and to improve function. In addition, disease-modifying antirheumatic drugs (DMARDs) may reduce disease progression.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments in people with rheumatoid arthritis who have not previously received any disease-modifying antirheumatic drug treatment? How do different drug treatments compare in people with rheumatoid arthritis who have either not responded to or are intolerant of first-line disease-modifying antirheumatic drugs? We searched: Medline, Embase, The Cochrane Library and other important databases up to June 2005 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 62 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: adalimumab, anakinra, antimalarial drugs, azathioprine, ciclosporin, corticosteroids, cyclophosphamide, etanercept, infliximab plus methotrexate, leflunomide, methotrexate (alone; or plus sulfasalazine plus hydroxychloroquine), oral gold, parenteral gold, penicillamine, sulfasalazine.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Interleukin 1 Receptor Antagonist Protein; Methotrexate; Treatment Outcome
PubMed: 19454108
DOI: No ID Found