Comparison of effectiveness of interventions in reducing mortality in patients of toxic epidermal necrolysis: A network meta-analysis
Indian journal of dermatology, venereology and leprology. 2021;:1-17
BACKGROUND Limited evidence is available about effectiveness and choice of immunomodulating treatment modalities for toxic epidermal necrolysis (TEN). AIMS To compare the effectiveness of interventions to reduce mortality in patients of toxic epidermal necrolysis through network meta-analysis. METHODS Studies were retrieved using PubMed, Google Scholar and Cochrane Database of Systematic Reviews from inception to September 18, 2018. Only English language articles were considered. Observational and randomized controlled studies having ≥ 5 TEN patients in each intervention arm were included. Two investigators independently extracted study characteristics, intervention details and mortality data. Bayesian network meta-analysis was performed using the Markov chain Monte Carlo (MCMC) approach through the random effect model. The ranking analysis was done to provide a hierarchy of interventions. The consistency between direct and indirect evidence was assessed through node spit analysis. The primary outcome was to compare the mortality [Odds ratio OR (95% credibility interval CrI)] among all treatment modalities of TEN. RESULTS Twenty-four studies satisfying the selection criteria were included. The network analysis showed improved survival with cyclosporine as compared to supportive care [OR- 0.19 (95% CrI: 0.05, 0.59)] and intravenous immunoglobulin [OR- 0.21 (95% CrI: 0.05, 0.76)]. The hierarchy of treatments based on "surface under the cumulative ranking curves" (SUCRA) value were cyclosporine (0.93), steroid+intravenous immunoglobulin (0.76), etanercept (0.59), steroids (0.46), intravenous immunoglobulin (0.40), supportive care (0.34) and thalidomide (0.02). No inconsistencies between direct and indirect estimates were observed for any of the treatment pairs. LIMITATIONS Evidence is mainly based on retrospective studies. CONCLUSION The use of cyclosporine can reduce mortality in TEN patients. Other promising immunomodulators could be steroid+intravenous immunoglobulin combination and etanercept.
Scleromyxedema treatment: a systematic review and update
Int J Dermatol. 2020
IMPORTANCE Scleromyxedema is a chronic disease with high morbidity and mortality and no definitive therapeutic guidelines. OBJECTIVE To review all available data on the efficacy and the safety of the available treatments of scleromyxedema and suggest a possible therapeutic approach. EVIDENCE REVIEW We performed a systematic literature review in Pubmed/Medline, Embase, and Cochrane collaboration databases, searching for all articles since 1990 on the treatments of scleromyxedema, with no limits on participant age, gender, or nationality. FINDINGS Ninety-seven studies were included in this systematic review, of which one prospective, two retrospective, 70 case reports/case series, and 24 letters/correspondence/clinical image. Intravenous immunoglobulin (IVIG) was the most used first-line therapy based on its efficacy and its generally well-tolerated nature; most patients require continued treatment to remain in remission. Thalidomide and systemic glucocorticoids were mostly considered as second-line therapies and were given alone or in association with IVIG. Patients with severe or refractory disease were treated with autologous bone marrow transplantation, melphalan, or bortezomib with dexamethasone. CONCLUSIONS AND RELEVANCE Consideration of patient comorbidities, disease distribution, clinician experience, and treatment accessibility is mandatory in every therapeutic approach of scleromyxedema.
Systemic treatments in the management of atopic dermatitis: a systematic review and meta-analysis
BACKGROUND As an evidence resource for the currently planned European Academy of Allergy and Clinical Immunology (EAACI) clinical practice guideline "systemic treatment of atopic dermatitis (AD)" we critically appraised evidence on systemic treatments for moderate-to-severe AD. METHODS We systematically identified randomized controlled trials (RCTs) investigating the safety and efficacy of systemic treatments for AD up to February 2020. Primary efficacy outcomes were clinical signs, AD symptoms and health-related quality of life. Primary safety outcomes included cumulative incidence rates for (serious) adverse events. Trial quality was assessed applying the Cochrane Risk of Bias Tool 2.0. Meta-analyses were conducted where appropriate. RESULTS 50 RCTs totalling 6681 patients were included. Trial evidence was identified for Apremilast, Azathioprine (AZA), Baricitinib, Ciclosporin-A (CSA), corticosteroids, Dupilumab, Interferon-gamma, intravenous immunoglobulins (IVIG), Mepolizumab, Methotrexate (MTX), Omalizumab, Upadacitinib and Ustekinumab. Meta-analyses were indicated for the efficacy of Baricitinib [EASI75 RD 0.16, 95% CI (0.10;0.23)] and Dupilumab [EASI75, RD 0.37, 95% CI (0.32;0.42)] indicating short-term (i.e. 16-week treatment) superiority over placebo. Furthermore efficacy analyses of AZA and CSA indicated short-term superiority over placebo, however non-validated scores were used and can therefore not be compared to EASI. CONCLUSION The most robust, replicated high quality trial evidence is present for the efficacy and safety of Dupilumab for up to 1 year in adults. Robust trial evidence was further revealed for AZA, Baricitinib and CSA. Methodological restrictions led to limited evidence-based conclusions for all other systemic treatments. Head-to-head trials with novel systemic treatments are required to clarify the future role of conventional therapies.
Clinical factors influencing the response to intravenous immunoglobulin treatment in cases of treatment-resistant pyoderma gangrenosum
The Journal of dermatological treatment. 2019;:1-13
BACKGROUND Pyoderma gangrenosum (PG) is a neutrophilic disorder which classically presents as chronic, painful ulcers on the lower extremities. There is evidence supporting a potential role for intravenous immunoglobulin (IVIG) as adjuvant therapy for treatment-resistant cases; however, it is unclear which patients will most benefit from this modality of treatment - an especially important consideration given the cost per infusion ($5,000-$10,000). Thus, we sought to identify the clinical characteristics of patients with refractory PG lesions who demonstrated complete healing when IVIG was incorporated into the therapeutic plan. METHODS We performed a literature search of PubMed/MEDLINE and Embase using the keywords "pyoderma gangrenosum" and "IVIG". We also added four institutional cases. Descriptive statistics were used to analyze the data. Significance was set at p < 0.05. RESULTS We discovered a total of 45 cases. Twenty-three patients with treatment-resistant PG had complete healing, 22 had partial or unhealed PG ulcers. Patients with one ulcer were 4.1 (95% CI: 1.1 to 18.5) times more likely to achieve complete healing than patients with more than one ulcer, when IVIG was added (p = 0.041). CONCLUSION There is increased efficacy of IVIG as a treatment for patients with a solitary treatment-resistant PG lesion compared to patients with multiple refractory lesions.