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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 For Immunotherapy of Cancer Jan 2024Immune checkpoint inhibitor (ICI) treatment has become an important therapeutic option for various cancer types. Although the treatment is effective, ICI can...
Immune checkpoint inhibitor (ICI) treatment has become an important therapeutic option for various cancer types. Although the treatment is effective, ICI can overstimulate the patient's immune system, leading to potentially severe immune-related adverse events (irAEs), including hepatitis, colitis, pneumonitis and myocarditis. The initial mainstay of treatments includes the administration of corticosteroids. There is little evidence how to treat steroid-resistant (sr) irAEs. It is mainly based on small case series or single case reports. This systematic review summarizes available evidence about sr-irAEs. We conducted a systematic literature search in PubMed. Additionally, we included European Society for Medical Oncology, Society for Immunotherapy of Cancer, National Comprehensive Cancer Network and American Society of Clinical Oncology Guidelines for irAEs in our assessment. The study population of all selected publications had to include patients with cancer who developed hepatitis, colitis, pneumonitis or myocarditis during or after an immunotherapy treatment and for whom corticosteroid therapy was not sufficient. Our literature search was not restricted to any specific cancer diagnosis. Case reports were also included. There is limited data regarding life-threatening sr-irAEs of colon/liver/lung/heart and the majority of publications are single case reports. Most publications investigated sr colitis (n=26), followed by hepatitis (n=21), pneumonitis (n=17) and myocarditis (n=15). There is most data for mycophenolate mofetil (MMF) to treat sr hepatitis and for infliximab, followed by vedolizumab, to treat sr colitis. Regarding sr pneumonitis there is most data for MMF and intravenous immunoglobulins (IVIG) while data regarding infliximab are conflicting. In sr myocarditis, most evidence is available for the use of abatacept or anti-thymocyte globulin (ATG) (both with or without MMF) or ruxolitinib with abatacept. This review highlights the need for prompt recognition and treatment of sr hepatitis, colitis, pneumonitis and myocarditis. Guideline recommendations for sr situations are not defined precisely. Based on our search, we recommend-as first line treatment-(1) MMF for sr hepatitis, (2) infliximab for sr colitis, followed by vedolizumab, (3) MMF and IVIG for sr pneumonitis and (4) abatacept or ATG (both with or without MMF) or ruxolitinib with abatacept for sr myocarditis. These additional immunosuppressive agents should be initiated promptly if there is no sufficient response to corticosteroids within 3 days.
Topics: Humans; Abatacept; Adrenal Cortex Hormones; Colitis; Hepatitis; Immunoglobulins, Intravenous; Infliximab; Mycophenolic Acid; Myocarditis; Neoplasms; Nitriles; Pneumonia; Pyrazoles; Pyrimidines
PubMed: 38233099
DOI: 10.1136/jitc-2023-007409 -
Innovations in Clinical Neuroscience 2022Neuromyelitis optica spectrum disorder (NMOSD) is a neurological condition consisting of relapse-related disability. Treatment options are limited. This systematic... (Review)
Review
Comparative Analysis of Treatment Outcomes in Patients with Neuromyelitis Optica Spectrum Disorder Treated with Rituximab, Azathioprine, and Mycophenolate Mofetil: A Systematic Review and Meta-analysis.
INTRODUCTION
Neuromyelitis optica spectrum disorder (NMOSD) is a neurological condition consisting of relapse-related disability. Treatment options are limited. This systematic review and meta-analysis aimed to evaluate the effectiveness and tolerability of rituximab (RTX) in comparison to azathioprine (AZT) and mycophenolate mofetil (MMF) for the treatment of NMOSD.
METHODS
A systematic search was conducted among electronic databases, including PubMed, Scopus, EBSCO, and Cochrane, for relevant studies. We included randomized, controlled trials and prospective and retrospective studies evaluating the efficacy and safety of RTX compared to AZT and/or MMF in adult and pediatric patients with NMOSD. The Newcastle-Ottawa Scale (NOS) and Cochrane Collaboration tool were used to determine the risk of bias.
RESULTS
Eleven studies involving 1,086 patients were included in our study. Treatment with RTX generally yielded favorable annualized relapse rate (ARR) and Expanded Disability Status Scale (EDSS) results in comparison to AZT and MMF, despite its variable statistical significance. RTX treatment reduced the relapse rate and hazard risk for relapse (HRR). Patients in the RTX group experienced significantly fewer adverse events, among which the most common were allergies, infections, and leukopenia.
CONCLUSION
In this study, RTX appeared to be superior to AZT and MMF in improving disability and reducing relapse in patients with NMOSD. RTX is also associated with fewer adverse events based on pooled analysis. Future randomized clinical trials are needed to establish the efficacy and safety of RTX in patients with NMOSD.
PubMed: 35958974
DOI: No ID Found -
Drugs Feb 2015While a variety of intervention options have been described for pemphigus vulgaris, the optimal treatment strategy has not been established. (Review)
Review
BACKGROUND
While a variety of intervention options have been described for pemphigus vulgaris, the optimal treatment strategy has not been established.
OBJECTIVES
The objective of this systematic review is to assess the literature on the efficacy and safety of interventions for the treatment of pemphigus vulgaris.
DATA SOURCES
Five electronic databases were searched, including The Cochrane Skin Group's Specialized Register, The Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDLINE and Latin American and Caribbean Health science Information database (LILACS). Five trial registers as well as reference lists of included RCTs were also searched.
STUDY ELIGIBILITY CRITERIA
Any published randomised controlled trial (RCT) on intervention for pemphigus vulgaris was included, provided the diagnosis of pemphigus vulgaris was confirmed with appropriate clinical features, histopathology and immunofluorescence studies. Studies which included forms of pemphigus other than pemphigus vulgaris were excluded.
INTERVENTIONS
Altogether 18 RCTs were identified including 16 distinct interventions.
STUDY APPRAISAL AND SYNTHESIS METHODS
Included studies were assessed for patient selection, methods of randomisation, blinding, follow-up and selective reporting.
RESULTS
Current evidence is incomplete and inconclusive. The interventions which appear promising, but will require further evaluation include adjuvant mycophenolate mofetil (MMF), azathioprine, intravenous immunoglobulins (IVIG), sulfasalazine and pentoxifylline, infliximab, epidermal growth factor and pimecrolimus. Interventions with inconclusive evidence include high (120-180 mg) versus low (45-60 mg) prednisone dosage, pulsed dexamethasone, cyclophosphamide, dexamethasone-cyclophosphamide pulse therapy (DCP), cyclosporine, dapsone, etanercept, acyclovir and tacrolimus.
LIMITATIONS
Our review is limited by the small number of high-quality RCTs and variety of outcome measures, precluding the performing of a meta-analysis.
CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS
The optimal treatment strategy for pemphigus vulgaris remains unclear. Higher quality RCTs are required in the future to re-evaluate many interventions and to explore other unstudied interventions.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Dose-Response Relationship, Drug; Glucocorticoids; Humans; Immunologic Factors; Pemphigus; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 25655250
DOI: 10.1007/s40265-015-0353-6 -
The Cochrane Database of Systematic... Mar 2015Multifocal motor neuropathy (MMN) is characterised by progressive, predominantly distal, asymmetrical limb weakness and usually multiple partial motor nerve conduction... (Review)
Review
BACKGROUND
Multifocal motor neuropathy (MMN) is characterised by progressive, predominantly distal, asymmetrical limb weakness and usually multiple partial motor nerve conduction blocks. Intravenous immunoglobulin (IVIg) is beneficial but the role of immunosuppressive agents is uncertain. This is an update of a review first published in 2002 and previously updated in 2003, 2005, 2008 and 2011.
OBJECTIVES
To assess the effects of immunosuppressive agents for the treatment of multifocal motor neuropathy.
SEARCH METHODS
On 22 September 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE and LILACS for trials of MMN. We also searched two trials registers for ongoing studies.
SELECTION CRITERIA
We planned to include randomised controlled trials (RCTs) and quasi-RCTs. We considered prospective and retrospective case series and case reports in the Discussion.
DATA COLLECTION AND ANALYSIS
Two review authors searched the titles and abstracts of the articles identified and extracted the data independently.
MAIN RESULTS
Only one RCT of an immunosuppressive or immunomodulatory agent has been performed in MMN. This study randomised 28 participants and showed that mycophenolate mofetil, when used with IVIg, did not significantly improve strength, function or reduce the need for IVIg. No serious adverse events were observed. The study was deemed at low risk of bias. We summarised the results of retrospective and prospective case series in the discussion.
AUTHORS' CONCLUSIONS
According to moderate quality evidence, mycophenolate mofetil did not produce significant benefit in terms of reducing need for IVIg or improving muscle strength in MMN. Trials of other immunosuppressants should be undertaken.
Topics: Drug Therapy, Combination; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Immunosuppressive Agents; Motor Neuron Disease; Muscle Strength; Mycophenolic Acid; Polyneuropathies; Randomized Controlled Trials as Topic
PubMed: 25739040
DOI: 10.1002/14651858.CD003217.pub5 -
Journal of Clinical Rheumatology :... Oct 2023To develop the first evidence-based Pan American League of Associations for Rheumatology (PANLAR) guidelines for the treatment of Takayasu arteritis (TAK).
OBJECTIVE
To develop the first evidence-based Pan American League of Associations for Rheumatology (PANLAR) guidelines for the treatment of Takayasu arteritis (TAK).
METHODS
A panel of vasculitis experts developed a series of clinically meaningful questions addressing the treatment of TAK patients in the PICO (population/intervention/comparator/outcome) format. A systematic literature review was performed by a team of methodologists. The evidence quality was assessed according to the GRADE (Grading of Recommendations/Assessment/Development/Evaluation) methodology. The panel of vasculitis experts voted each PICO question and made recommendations, which required ≥70% agreement among the voting members.
RESULTS
Eleven recommendations were developed. Oral glucocorticoids are conditionally recommended for newly diagnosed and relapsing TAK patients. The addition of nontargeted synthetic immunosuppressants (e.g., methotrexate, leflunomide, azathioprine, or mycophenolate mofetil) is recommended for patients with newly diagnosed or relapsing disease that is not organ- or life-threatening. For organ- or life-threatening disease, we conditionally recommend tumor necrosis factor inhibitors (e.g., infliximab or adalimumab) or tocilizumab with consideration for short courses of cyclophosphamide as an alternative in case of restricted access to biologics. For patients relapsing despite nontargeted synthetic immunosuppressants, we conditionally recommend to switch from one nontargeted synthetic immunosuppressant to another or to add tumor necrosis factor inhibitors or tocilizumab. We conditionally recommend low-dose aspirin for patients with involvement of cranial or coronary arteries to prevent ischemic complications. We strongly recommend performing surgical vascular interventions during periods of remission whenever possible.
CONCLUSION
The first PANLAR treatment guidelines for TAK provide evidence-based guidance for the treatment of TAK patients in Latin American countries.
Topics: Humans; United States; Takayasu Arteritis; Tumor Necrosis Factor Inhibitors; Rheumatology; Immunosuppressive Agents; Methotrexate
PubMed: 37553869
DOI: 10.1097/RHU.0000000000002004 -
Annals of the American Thoracic Society Jan 2024The American Thoracic Society convened an international, multidisciplinary panel to develop clinical practice guidelines for the treatment of systemic... (Meta-Analysis)
Meta-Analysis
The American Thoracic Society convened an international, multidisciplinary panel to develop clinical practice guidelines for the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD). To conduct a systematic review and evaluate the literature to determine whether patients with SSc-ILD should be treated with mycophenolate. A literature search was conducted across the MEDLINE, EMBASE, and CENTRAL databases through June 2022 for studies using mycophenolate to treat patients with SSc-ILD. Mortality, disease progression, quality of life, and adverse event data were extracted, and meta-analyses were performed when possible. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group method was used to assess the quality of evidence. The literature review resulted in seven studies fitting the inclusion criteria. The systematic review and meta-analyses revealed changes in forced vital capacity % predicted (mean difference [MD], 5.4%; 95% confidence interval [95% CI]: 3.3%, 7.5%), diffusing capacity of the lung for carbon monoxide % predicted (MD, 4.64%; 95% CI: 0.54%, 8.74%), and breathlessness score (MD, 1.99; 95% CI: 0.36, 3.62) favored mycophenolate over placebo. The risk of anemia (relative risk [RR], 2.3; 95% CI: 1.2, 71.4) was higher with mycophenolate. There were no significant differences between mycophenolate and cyclophosphamide, except risk of premature discontinuation (RR, 0.6; 95% CI: 0.4, 0.9), and leukopenia (RR, 0.1; 95% CI: 0.05, 0.4) favored mycophenolate. The quality of evidence was moderate to very low per GRADE. Mycophenolate use in patients with SSc-ILD is associated with statistically significant improvements in disease progression and quality-of-life measures compared with placebo. There were no differences in mortality, disease progression, or quality of life compared with cyclophosphamide, but there were fewer adverse events. The quality of evidence is very low.
Topics: Humans; Quality of Life; Lung Diseases, Interstitial; Mycophenolic Acid; Scleroderma, Systemic; Immunosuppressive Agents; Cyclophosphamide; Lung; Disease Progression
PubMed: 37027538
DOI: 10.1513/AnnalsATS.202301-054OC -
British Journal of Clinical Pharmacology Feb 2022Mycophenolic acid (MPA) is an immunosuppressive drug commonly used for prophylaxis of graft rejection in solid organ transplant recipients. The main concern with the... (Meta-Analysis)
Meta-Analysis Review
AIM
Mycophenolic acid (MPA) is an immunosuppressive drug commonly used for prophylaxis of graft rejection in solid organ transplant recipients. The main concern with the prolonged use of immunosuppressive drugs is the risk of developing cancer. However, it remains unclear whether the immunosuppressive regimens containing MPA confer an increased degree of cancer risk. The present study aimed to determine the association between MPA exposure and the incidence of cancer in solid organ transplant recipients.
METHODS
A systematic search was performed on the PubMed, EMBASE and Cochrane Library databases. Relevant articles that had findings on the incidence (or event) of cancer in cohorts with and without MPA exposure were retrieved for data extraction. A meta-analysis was conducted by means of the random-effects model, and the relative risk (RR) and its 95% confidence interval (95% CI) were used as a summary effect measure.
RESULTS
A total of 39 studies were eligible for inclusion, with 32 studies that enabled meta-analysis. MPA exposure was significantly associated with a lower risk of cancer when compared to azathioprine exposure (RR = 0.66, 95% CI = 0.53-0.81, P < .001) or no exposure to any additional treatments (RR = 0.85, 95% CI = 0.73-0.99, P = .04). There was no significant difference in cancer risk for the comparison between MPA exposure and mammalian target of rapamycin (mTOR) inhibitor exposure (RR = 1.54, 95% CI = 0.96-2.46, P = .07).
CONCLUSIONS
MPA exposure was not associated with an increased risk of cancer and may even be associated with a lower risk of cancer when compared to azathioprine or no treatment.
Topics: Azathioprine; Graft Rejection; Humans; Immunosuppressive Agents; Mycophenolic Acid; Neoplasms; Organ Transplantation; Risk
PubMed: 34240462
DOI: 10.1111/bcp.14979 -
American Journal of Clinical Dermatology Dec 2014No optimal therapeutic approach has been established for pemphigus. (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
No optimal therapeutic approach has been established for pemphigus.
OBJECTIVE
Our objective was to evaluate the efficacy, steroid-sparing effect, and safety of available treatment modalities.
METHODS
PubMed, LILACS (up to July 2014), the Cochrane Central Register of Controlled Trials (CENTRAL, issue 5 of 12, May 2014), and the ClinicalTrials.gov registry and reference lists were searched for randomized controlled trials of any treatment modality for pemphigus vulgaris and pemphigus foliaceus. Data were extracted independently by two authors using predefined appraisal criteria and data fields.
RESULTS
A total of 20 studies (826 participants) were included. Most were small and open-labeled; all but seven were not concealed for allocation. Owing to the variability in intervention arms, five meta-analyses were performed, each pooling the data of two to three trials. Studies excluded from the meta-analyses were described quantitatively. Azathioprine had a steroid-sparing effect but did not increase remission rate. Mycophenolate mofetil induced sustained remission more quickly than did placebo and delayed time to relapse but did not have a steroid-sparing effect or favorable remission rate. Cyclophosphamide had a steroid-sparing effect, though less than azathioprine, but did not affect the remission rate or time-to-disease control. Intravenous immunoglobulin had more favorable short-term efficacy than did placebo. Topical epidermal growth factor hastened lesion healing.
CONCLUSIONS
Although some of the available therapeutic modalities for pemphigus are beneficial in terms of steroid-sparing, hastening response, or delaying relapse, none were found to increase the complete response rate compared with glucocorticoids alone, currently the mainstay of treatment. Multicenter randomized controlled trials and case control studies with uniform outcome measures are warranted.
Topics: Glucocorticoids; Humans; Immunosuppressive Agents; Pemphigus; Recurrence; Remission Induction
PubMed: 25403548
DOI: 10.1007/s40257-014-0101-9 -
Skin Research and Technology : Official... Mar 2024The purpose of this study is to investigate the effectiveness and safety of oral and injectable systemic treatments, such as methotrexate, azathioprine, cyclosporine,... (Review)
Review
AIMS AND OBJECTIVES
The purpose of this study is to investigate the effectiveness and safety of oral and injectable systemic treatments, such as methotrexate, azathioprine, cyclosporine, tofacitinib, baricitinib, corticosteroids, statins, zinc, apremilast, etc., for treating vitiligo lesions.
METHOD
Databases including PubMed, Scopus, and Web of Science were meticulously searched for studies spanning from 2010 to August 2023, focusing on systemic oral and injectable therapies for vitiligo, using comprehensive keywords and search syntaxes tailored to each database. Key data extracted included study design, treatment efficacy, patient outcomes, patient satisfaction, and safety profiles.
RESULTS
In a total of 42 included studies, oral mini-pulse corticosteroid therapy (OMP) was the subject of six studies (14.2%). Minocycline was the focus of five studies (11.9%), while methotrexate, apremilast, and tofacitinib each were examined in four studies (9.5%). Antioxidants and Afamelanotide were the subjects of three studies each (7.1%). Cyclosporine, simvastatin, oral zinc, oral corticosteroids (excluding OMP) and injections, and baricitinib were each explored in two studies (4.8%). Azathioprine, mycophenolate mofetil, and Alefacept were the subjects of one study each (2.4%).
CONCLUSION
Systemic treatments for vitiligo have been successful in controlling lesions without notable side effects. OMP, Methotrexate, Azathioprine, Cyclosporine, Mycophenolate mofetil, Simvastatin, Apremilast, Minocycline, Afamelanotide, Tofacitinib, Baricitinib, Antioxidants, and oral/injectable corticosteroids are effective treatment methods. However, oral zinc and alefacept did not show effectiveness.
Topics: Humans; Methotrexate; Azathioprine; Vitiligo; Mycophenolic Acid; Minocycline; Alefacept; Cyclosporine; Adrenal Cortex Hormones; Hypopigmentation; Simvastatin; Zinc; Purines; Pyrazoles; Sulfonamides; Azetidines; Thalidomide
PubMed: 38454597
DOI: 10.1111/srt.13642