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Chest Mar 2016Idiopathic pulmonary fibrosis (IPF) is a form of chronic progressive fibrosing interstitial lung disease of unknown origin. Recently, nintedanib and pirfenidone... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Idiopathic pulmonary fibrosis (IPF) is a form of chronic progressive fibrosing interstitial lung disease of unknown origin. Recently, nintedanib and pirfenidone demonstrated efficacy in slowing disease progression and were approved by the US Food and Drug Administration. Although numerous treatments have been evaluated in IPF, none have shown significant decreases in mortality. The objective of this study was to identify all pharmacologic treatments evaluated for IPF and analyze their efficacy via Bayesian network meta-analysis and pairwise indirect treatment comparisons. This review did not evaluate the effect of steroid therapy.
METHODS
We searched MEDLINE, Embase, and the Cochrane Library for studies published on or before August 2014. Studies were required to contain a randomized evaluation of nonsteroidal drug therapy for treatment of IPF and be published in English. Key outcomes of interest for this analysis were pulmonary function as measured by FVC as well as all-cause and respiratory-specific death. All outcomes were analyzed via a Bayesian framework.
RESULTS
Our review identified 30 eligible studies that evaluated 16 unique treatments. Under both the fixed-effect and random-effect models for respiratory-specific mortality, no treatments performed better than placebo. For all-cause mortality, pirfenidone and nintedanib had effects approaching significance with credible intervals slightly crossing the null under a fixed-effect model. Notably, for respiratory-specific mortality, all-cause mortality, and decline in percent predicted FVC, nintedanib and pirfenidone were virtually indistinguishable and no clear advantage was detected.
CONCLUSIONS
Although two treatments have been approved for IPF on the basis of reduced decline in pulmonary function, neither one has a clear advantage on mortality outcomes.
Topics: Acetylcysteine; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Azathioprine; Bayes Theorem; Bosentan; Endothelin Receptor Antagonists; Enzyme Inhibitors; Etanercept; Free Radical Scavengers; Humans; Idiopathic Pulmonary Fibrosis; Imatinib Mesylate; Immunosuppressive Agents; Indoles; Interferon-gamma; Phenylpropionates; Pyridazines; Pyridones; Pyrimidines; Recombinant Proteins; Sulfonamides; Vital Capacity; Warfarin
PubMed: 26836914
DOI: 10.1016/j.chest.2015.11.013 -
The Journal of Dermatological Treatment Dec 2020For severe cases of atopic dermatitis, systemic or potent agents may be required for control of disease. There have been some reports of treatment efficacy of off-label... (Meta-Analysis)
Meta-Analysis
For severe cases of atopic dermatitis, systemic or potent agents may be required for control of disease. There have been some reports of treatment efficacy of off-label use of mycophenolate mofetil (MMF) in patients with refractory atopic dermatitis or have developed adverse effects to initial systemic agents. Electronic searches were performed using six databases from their inception to April 2019. Data were extracted and analyzed according to predefined clinical endpoints. From 140 cases, the mean age was 38.21 ± 22.8 years. There were 52.9% males and 47.1% females. The average number of failed agents was 3.5 ± 1.2. 77.6% reported partial or full remission. Relapses occurred in 8.2% of cases. The average time for initial effects was 6.8 ± 7 weeks. There was a significant reduction in pre to post SCORAD scores by 18 points ( = .0002). More males had complications compared to females. Prolonged duration of treatment ≥1 year was associated with herpes infections. In summary, the current evidence to date is low-quality in nature but is promising regarding the efficacy and safety of MMF for adult and pediatric atopic dermatitis. There should be ongoing monitoring for infections that may develop on long term therapy.
Topics: Adolescent; Adult; Analysis of Variance; Dermatitis, Atopic; Enzyme Inhibitors; Female; Humans; IMP Dehydrogenase; Male; Mycophenolic Acid; Off-Label Use; Remission Induction
PubMed: 31294617
DOI: 10.1080/09546634.2019.1642996 -
International Urology and Nephrology May 2016To evaluate the efficacy and safety of the calcineurin inhibitors (CNIs) cyclosporine (CyA) and tacrolimus (TAC) in the induction and maintenance treatment of lupus... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To evaluate the efficacy and safety of the calcineurin inhibitors (CNIs) cyclosporine (CyA) and tacrolimus (TAC) in the induction and maintenance treatment of lupus nephritis (LN).
METHODS
The Cochrane library, PubMed, Embase, and CENTRAL databases were searched and reviewed up to February 2015. Randomized controlled trials were analyzed using RevMan 5.2 software.
RESULTS
Ten randomized controlled trials were selected and included in this study according to our inclusion and exclusion criteria, and six were included in the meta-analysis. The analysis results indicated that, in induction treatment, no statistically significant difference was observed in the rates of complete remission (CR), partial remission (PR), or response between the CNIs and intravenous cyclophosphamide (ivCYC). However, the rates of adverse events such as infection (RR 0.65, P = 0.04), leukocytopenia (RR 0.32, P = 0.04), and menstruation disorder (RR 0.37, P = 0.01) following the use of the CNIs were remarkably lower than those after ivCYC. No differences in the CR, PR, infection, or leukocytopenia rates were observed between the CNIs and mycophenolate mofetil (MMF). In the maintenance treatment period, the relapse rate between the CNIs and azathioprine (AZA) was similar (RR 0.44, P = 0.27), while the leukocytopenia rate was lower with the CNIs (RR 0.26, P = 0.0005).
CONCLUSION
The efficacy of the CNIs CyA and TAC in induction therapy for lupus nephritis is comparable to ivCYC and MMF, and they are much safer than ivCYC. CNI treatment during the maintenance period was also as effective as AZA treatment, with a much lower risk of adverse effects. The CNIs CyA and TAC should be recommended for both induction and maintenance therapy of LN.
Topics: Azathioprine; Calcineurin Inhibitors; Cyclophosphamide; Cyclosporine; Humans; Immunosuppressive Agents; Induction Chemotherapy; Lupus Nephritis; Maintenance Chemotherapy; Mycophenolic Acid; Randomized Controlled Trials as Topic; Tacrolimus
PubMed: 26781720
DOI: 10.1007/s11255-015-1201-z -
Alimentary Pharmacology & Therapeutics Jan 2017Crohn's disease (CD) and ulcerative colitis (UC) have a progressive course leading to hospitalisation and surgery. The ability of existing therapies to alter disease... (Comparative Study)
Comparative Study Meta-Analysis Review
Systematic review with meta-analysis: comparative efficacy of immunosuppressants and biologics for reducing hospitalisation and surgery in Crohn's disease and ulcerative colitis.
INTRODUCTION
Crohn's disease (CD) and ulcerative colitis (UC) have a progressive course leading to hospitalisation and surgery. The ability of existing therapies to alter disease course is not clearly defined.
AIM
To investigate the comparative efficacy of currently available inflammatory bowel disease (IBD) therapies to reduce hospitalisation and surgery.
METHODS
We conducted a systematic review in MEDLINE/PubMed for randomised controlled trials (RCT) published between January 1980 and May 2016 examining efficacy of biological or immunomodulator therapy in IBD. We performed direct comparisons of pooled proportions of hospitalisation and surgery. Pair-wise comparisons using a random-effects Bayesian network meta-analysis were performed to assess comparative efficacy of different treatments.
RESULTS
We identified seven randomised controlled trials (5 CD; 2 UC) comparing three biologics and one immunomodulator with placebo. In CD, anti-TNF biologics significantly reduced hospitalisation [Odds ratio (OR) 0.46, 95% confidence interval (CI) 0.36-0.60] and surgery (OR 0.23, 95% CI 0.13-0.42) compared to placebo. No statistically significant reduction was noted with azathioprine or vedolizumab. Azathioprine was inferior to both infliximab and adalimumab in preventing CD-related hospitalisation (>97.5% probability). Anti-TNF biologics significantly reduced hospitalisation (OR 0.48, 95% CI 0.29-0.80) and surgery (OR 0.67, 95% CI 0.46-0.97) in UC. There were no statistically significant differences in the pair-wise comparisons between active treatments.
CONCLUSIONS
In CD and UC, anti-TNF biologics are efficacious in reducing the odds of hospitalisation by half and surgery by 33-77%. Azathioprine and vedolizumab were not associated with a similar improvement, but robust conclusions may be limited due to paucity of RCTs.
Topics: Biological Products; Colitis, Ulcerative; Crohn Disease; Hospitalization; Humans; Immunosuppressive Agents; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 27862107
DOI: 10.1111/apt.13847 -
Seminars in Arthritis and Rheumatism Dec 2023Invasive fungal infections (IFIs) are life-threatening opportunistic infections in patients with connective tissue disease CTD) that cause significant morbidity and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Invasive fungal infections (IFIs) are life-threatening opportunistic infections in patients with connective tissue disease CTD) that cause significant morbidity and mortality. We attempted to determine the potential risk factors associated with IFIs in CTD.
METHODS
We systematically searched PubMed, Embase, and the Cochrane Library databases for relevant articles published from the database inception to February 1, 2023.
RESULTS
Twenty-six studies were included in this systematic review and meta-analysis. Risk factors identified for IFIs were diabetes (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.00 to 2.64), pulmonary diseases (OR 3.43; 95% CI 2.49 to 4.73), interstitial lung disease (ILD; OR, 4.06; 95% CI, 2.22 to 7.41), renal disease (OR, 4.41; 95% CI, 1.84 to 10.59), glucocorticoid (GC) use (OR, 4.15; 95% CI, 2.74 to 6.28), especially moderate to high-dose GC, azathioprine (AZA) use (OR, 1.50; 95% CI, 1.12 to 2.01), calcineurin inhibitor (CNI) use (OR, 2.49; 95% CI, 1.59 to 3.91), mycophenolate mofetil (MMF) use (OR, 2.83; 95% CI, 1.59 to 5.03), cyclophosphamide (CYC) use (OR, 3.35; 95% CI, 2.47 to 4.54), biologics use (OR, 3.43; 95% CI, 2.36 to 4.98), and lymphopenia (OR, 4.26; 95% CI, 2.08 to 8.73). Hydroxychloroquine (HCQ) use reduced risk of IFIs (OR, 0.67; 95% CI, 0.54 to 0.84). Furthermore, 17 of the 26 studies only reported risk factors for Pneumocystis jiroveci pneumonia (PJP) in patients with CTD. Pulmonary disease; ILD; and the use of GC, CNIs, CYC, methotrexate (MTX), MMF and biologics, and lymphopenia increased the risk of PJP, whereas the use of HCQ reduced its risk.
CONCLUSION
Diabetes, pulmonary disease, ILD, renal disease, use of GC (especially at moderate to high dose) and immunosuppressive drugs, and lymphopenia were found to be associated with significant risk for IFIs (especially PJP) in patients with CTD. Furthermore, the use of HCQ may reduce the risk of IFIs in patients with CTD.
Topics: Humans; Connective Tissue Diseases; Cyclophosphamide; Lung Diseases, Interstitial; Mycophenolic Acid; Glucocorticoids; Risk Factors; Diabetes Mellitus; Lymphopenia; Biological Products; Invasive Fungal Infections
PubMed: 37633041
DOI: 10.1016/j.semarthrit.2023.152257 -
BMC Pharmacology & Toxicology Nov 2014Idiopathic pulmonary fibrosis (IPF) is a life-limiting lung disease with considerable impact on patients and carers as the disease progresses. Currently few treatments... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Idiopathic pulmonary fibrosis (IPF) is a life-limiting lung disease with considerable impact on patients and carers as the disease progresses. Currently few treatments are available. We aimed to evaluate the clinical and cost-effectiveness of available treatments for IPF.
METHODS
Systematic reviews of clinical effectiveness, quality of life and cost effectiveness were undertaken. Eleven bibliographic databases were searched from inception to July 2013 and studies were assessed for eligibility against a set of pre-defined criteria. Two reviewers screened references, extracted data from included studies and appraised their quality. An advisory group was consulted about the choice of interventions. A narrative review was undertaken and where feasible fixed effect and random effects meta-analysis were undertaken including a network meta-analysis (NMA). A decision-analytic Markov model was developed to estimate cost-effectiveness of pharmacological treatments for IPF. Following best practice recommendations, the model perspective was of the national health service and personal social services, a discount rate of 3.5% for costs and health benefits was applied and outcomes were expressed as cost per quality adjusted life-year gained. Parameter values were obtained from the NMA and systematic reviews. Sensitivity analyses were undertaken.
RESULTS
Fourteen studies were included in the review of clinical effectiveness, of which one evaluated azathioprine, three N-acetylcysteine [NAC] (alone or in combination), four pirfenidone, one nintedanib, one sildenafil, one thalidomide, two pulmonary rehabilitation, and one a disease management programme. Study quality was generally good. Evidence suggests that some effective treatments are available. In NMA only nintedanib and pirfenidone show statistically significant improvements. The model results show increased survival for five pharmacological treatments (NAC triple therapy, inhaled NAC, nintedanib, pirfenidone, and sildenafil) compared with best supportive care, at increased cost. Only inhaled NAC was cost-effective at current willingness to pay thresholds but it may not be clinically effective.
CONCLUSIONS
Few interventions have any statistically significant effect and the cost-effectiveness of treatments is uncertain. A lack of studies on palliative care approaches was identified and there is a need for further research into pulmonary rehabilitation and thalidomide in particular. A well conducted RCT on inhaled NAC therapy should also be considered.
Topics: Cost-Benefit Analysis; Humans; Idiopathic Pulmonary Fibrosis; Models, Economic; Quality of Life; Treatment Outcome
PubMed: 25410822
DOI: 10.1186/2050-6511-15-63 -
Journal of Digestive Diseases Oct 2016To evaluate the efficacy and safety of low-dose azathioprine (AZA) in treating patients with chronic active ulcerative colitis (UC). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the efficacy and safety of low-dose azathioprine (AZA) in treating patients with chronic active ulcerative colitis (UC).
METHODS
A literature search of Medline, Embase, the Cochrane Library, Web of Science, Wanfang Database, CNKI, SinoMed, VIP Chinese Science and the Technology Journals Database was conducted to identify eligible studies that evaluated the efficacy and safety of low-dose azathioprine (AZA) in treating patients with chronic active UC published up to 15 July 2015. Data were extracted from the studies, including clinical efficacy (response rate, adverse drug reaction [ADR] rate, steroid withdrawal rate and relapse rate) and endoscopic improvement (endoscopic remission rate and mucosal healing rate).
RESULTS
Six studies with 211 patients were eligible for the analysis. The overall response rates after 6 and 12 months of treatment were 78.0% (95% confidence interval [CI] 71.0-85.0%) and 88.0% (95% CI 80.0-96.0%), respectively. The overall ADR rate was 25.0% (95% CI 18.0-31.0%). Endoscopic response rate was around 85.0%, while the endoscopic remission rates and mucosal healing rates after 6 and 12 months of treatment were above 60.0% and 70.0%, respectively. The steroid withdrawal rate and relapse rate were in moderate to high heterogeneity. Egger's test indicated that there was no publication bias for studies regarding the 6-month response rate and ADR rate.
CONCLUSIONS
Low-dose AZA is effective and safe in the treatment of chronic active UC patients. However, randomized controlled trials with large sample sizes are needed to draw definitive conclusions.
Topics: Azathioprine; Chronic Disease; Colitis, Ulcerative; Colonoscopy; Drug Administration Schedule; Drug Therapy, Combination; Glucocorticoids; Humans; Immunosuppressive Agents; Publication Bias; Treatment Outcome; Wound Healing
PubMed: 27450969
DOI: 10.1111/1751-2980.12386 -
Health Technology Assessment... Mar 2015Idiopathic pulmonary fibrosis (IPF) is a life-limiting lung disease that generally affects people over 60 years old. The main symptoms are shortness of breath and cough,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Idiopathic pulmonary fibrosis (IPF) is a life-limiting lung disease that generally affects people over 60 years old. The main symptoms are shortness of breath and cough, and as the disease progresses there is a considerable impact on day-to-day life. Few treatments are currently available.
OBJECTIVES
To conduct a systematic review of clinical effectiveness and an analysis of cost-effectiveness of treatments for IPF based on an economic model informed by systematic reviews of cost-effectiveness and quality of life.
DATA SOURCES
Eleven electronic bibliographic databases, including MEDLINE, EMBASE, Web of Science, and The Cochrane Library and the Centre for Reviews and Dissemination databases, were searched from database inception to July 2013. Reference lists of relevant publications were also checked and experts consulted.
METHODS
Two reviewers independently screened references for the systematic reviews, extracted and checked data from the included studies and appraised their risk of bias. An advisory group was consulted about the choice of interventions until consensus was reached about eligibility. A narrative review with meta-analysis was undertaken, and a network meta-analysis (NMA) was performed. A decision-analytic Markov model was developed to estimate cost-effectiveness of pharmacological treatments for IPF. Parameter values were obtained from NMA and systematic reviews. Univariate and probabilistic sensitivity analyses were undertaken. The model perspective is NHS and Personal Social Services, and discount rate is 3.5% for costs and health benefits.
RESULTS
Fourteen studies were included in the review of clinical effectiveness, of which one evaluated azathioprine, three N-acetylcysteine (NAC) (alone or in combination), four pirfenidone, one BIBF 1120, one sildenafil, one thalidomide, two pulmonary rehabilitation, and one a disease management programme. Study quality was generally good, with a low risk of bias. The current evidence suggests that some treatments appear to be clinically effective. The model base-case results show increased survival for five pharmacological treatments, compared with best supportive care, at increased cost. General recommendations cannot be made of their cost-effectiveness owing to limitations in the evidence base.
LIMITATIONS
Few direct comparisons of treatments were identified. An indirect comparison through a NMA was performed; however, caution is recommended in the interpretation of these results. In relation to the economic model, there is an assumption that pharmacological treatments have a constant effect on the relative rate of per cent predicted forced vital capacity decline.
CONCLUSIONS
Few interventions have any statistically significant effect on IPF and a lack of studies on palliative care approaches was identified. Research is required into the effects of symptom control interventions, in particular pulmonary rehabilitation and thalidomide. Other research priorities include a well-conducted randomised controlled trial on inhaled NAC therapy and an updated evidence synthesis once the results of ongoing studies are reported.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42012002116.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Cost-Benefit Analysis; Humans; Idiopathic Pulmonary Fibrosis; Models, Economic; Treatment Outcome
PubMed: 25760991
DOI: 10.3310/hta19200 -
Lupus Sep 2023Neurological involvement can occur in systemic lupus erythematosus (SLE) due to co-existing neuromyelitis optica spectrum disorder (NMOSD). The symptoms can mimic those...
BACKGROUND
Neurological involvement can occur in systemic lupus erythematosus (SLE) due to co-existing neuromyelitis optica spectrum disorder (NMOSD). The symptoms can mimic those of neuropsychiatric manifestations of SLE. Pathogenic anti-aquaporin-4 (AQP4) antibodies, commonly found in NMOSD, are responsible for the neuroinflammatory response and secondary demyelinating lesions. These anti-AQP4 antibodies can be the drivers of neuroinflammatory process in SLE patients, which is distinct from the immunopathogenesis seen in traditional neuropsychiatric SLE. The clinical course is often a relapsing one and is managed differently. In this review, we describe and outline the clinical course and outcomes of AQP4+ NMOSD/SLE overlap cases.
METHODS
To investigate the co-existence of SLE with AQP4+NMOSD, we conducted a systematic review of individual patient data from case reports and case series reported in major databases. The study extracted clinic-demographic features, imaging and laboratory profiles, treatment approaches, and outcomes of these patients. Inclusion criteria for the review required patients to have positivity for AQP4 or NMO in the blood and/or cerebrospinal fluid (CSF) and exhibit at least one manifestation of both NMOSD and SLE.
RESULTS
In this overlap between SLE and AQP4+NMOSD, a high female preponderance was observed, with 42 out of 46 patients (91.3%) being female. Nearly half of the NMOSD cases (47.8%) had onset after lupus, with a median of 5 years between the two diagnoses. Hematological manifestations were seen in the majority of patients (63%), as well as longitudinally extensive transverse myelitis (87%), and brainstem involvement on imaging (29.6%). Cerebrospinal fluid analysis showed a dominantly lymphocytic pleocytosis, with oligoclonal bands being reported scarcely. Although cyclophosphamide was the most common steroid sparing agent used for maintenance, robust evidence for both efficacy and safety in AQP4+NMOSD is available for mycophenolate mofetil, azathioprine, and rituximab. The majority of reported cases showed a relapsing course, while one patient had a monophasic course.
CONCLUSION
AQP4+NMOSD in SLE patients is a relapsing and neurologically disabling disorder that can mimic neuropsychiatric manifestations, frequently occurs after the onset of lupus or may predate, responds to immunosuppressants, and necessitates indefinite treatment.
Topics: Humans; Female; Male; Neuromyelitis Optica; Lupus Erythematosus, Systemic; Neoplasm Recurrence, Local; Aquaporin 4; Syndrome; Disease Progression; Autoantibodies
PubMed: 37487596
DOI: 10.1177/09612033231191180 -
Expert Opinion on Pharmacotherapy Jun 2009The systemic vasculitides are characterized by inflammatory lesions in blood vessels. Therapeutic approaches should be based on the aetiology or pathophysiology of... (Review)
Review
The systemic vasculitides are characterized by inflammatory lesions in blood vessels. Therapeutic approaches should be based on the aetiology or pathophysiology of disease. Unfortunately, for many of these disorders neither is fully understood and empirical treatment based on clinical presentation and the pattern of organ involvement is used. This approach is effective in improving survival in the most serious forms. We undertook a systematic literature review to assess the evidence for using drug therapies in vasculitis. Glucocorticoids remain essential for many forms of vasculitis; indeed, in giant-cell arteritis, they may be the only therapy necessary. However, additional immunosuppressive agents are required for other forms of vasculitis: methotrexate in Takayasu's arteritis and non-renal small-vessel vasculitis and cyclophosphamide for classic Wegener's granulomatosis, microscopic polyangiitis, polyarteritis nodosa and Churg-Strauss syndrome with poor prognostic features. Subsequent disease control is with low-dose glucocorticoid and azathioprine or methotrexate. Biologic therapy is being used in resistant cases. Patients experience significant short- to medium-term toxicity, especially infection and steroid side effects. Late sequelae due to high cumulative doses of cyclophosphamide include infertility and malignancy. Such risks are being reduced due to more judicious use of short courses of cyclophosphamide followed by substitution by safer agents.
Topics: Humans; Vasculitis
PubMed: 19445559
DOI: 10.1517/14656560902946401