Project description:IntroductionThe long-term benefit-risk profiles of licensed and investigational treatments for moderate-to-severe plaque psoriasis have not been fully characterized.MethodsRandomized controlled trials (RCTs) of licensed and investigational treatments for moderate-to-severe plaque psoriasis were identified through a systematic literature review through 2 May 2021. Bayesian network meta-analyses (NMAs) were conducted to compare the efficacy (Psoriasis Area and Severity Index [PASI] 75/90/100 [at least a 75/90/100% reduction in PASI score from baseline] response) and safety outcomes (any adverse event [AE], any serious AE [SAE], and AEs leading to treatment discontinuation) of each treatment evaluated between weeks 48 and 56 after baseline. Surfaces under the cumulative ranking curves (SUCRAs) were calculated to evaluate the relative ranking of treatments. The benefit-risk profiles of treatments were assessed by bidimensional plots of the NMA-estimated efficacy and safety outcomes.ResultsIn the efficacy NMA (N = 14 RCTs), the relative rankings for PASI 75/90/100 responses by weeks 48-56 were the highest for risankizumab (SUCRA: 98.5%) and bimekizumab (83.8% for dosing every 4 weeks [Q4W], 72.7% for dosing Q4W then every 8 weeks). The PASI response rates did not differ significantly between risankizumab and the two bimekizumab regimens. Additionally, risankizumab was associated with significantly higher PASI response rates than brodalumab, guselkumab, ixekizumab, secukinumab, ustekinumab, adalimumab, and etanercept. In the safety NMAs (N = 8 RCTs), risankizumab had the highest relative rankings for all three outcomes (SUCRA: 92.1%, 82.0%, and 91.0% for any AE, any SAE, and AEs leading to treatment discontinuation, respectively). Risankizumab had a significantly lower rate of any AE than bimekizumab, ustekinumab, and secukinumab.ConclusionsRisankizumab was associated with the most favorable long-term benefit-risk profile for the treatment of moderate-to-severe plaque psoriasis. Although ixekizumab and bimekizumab had favorable efficacy profiles, both treatments had lower rankings for safety outcomes.

Project description:ImportanceThe clinical benefits of novel treatments for moderate to severe psoriasis are well established, but wide variations exist in patient response across different therapies. In the absence of head-to-head randomized trials, meta-analyses synthesizing data from multiple studies are needed to assess comparative efficacy among psoriasis treatments.ObjectiveTo estimate the relative short-term and long-term efficacy of biologics and oral agents for the treatment of moderate to severe psoriasis.Data sourcesA systematic literature review was conducted on December 4, 2017, and updated on September 17, 2018. The Embase, MEDLINE, and Cochrane Central Register databases were included.Study selectionPhase 2, 3, or 4 randomized clinical trials of treatments licensed by the US Food and Drug Administration and the European Medicines Agency for adults with moderate to severe psoriasis with data on Psoriasis Area and Severity Index assessment of 75%, 90%, and 100% reductions (PASI 75, 90, and 100) at 10 to 16 weeks (short-term efficacy) or 44 to 60 weeks (long-term efficacy) from baseline.Data extraction and synthesisData were extracted based on the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. A bayesian network meta-analysis was conducted to estimate short-term PASI response rates; to account for variation across trials, an ordinal model that adjusted for reference arm response was implemented. The long-term PASI rates were estimated via a traditional meta-analysis.Main outcomes and measuresPASI 75, 90, and 100 response rates at 10 to 16 weeks and 44 to 60 weeks from baseline.ResultsSixty trials meeting all inclusion criteria were included. At weeks 10 to 16, the highest PASI 90 rates were seen with risankizumab-rzaa (71.6%; 95% credible interval [CrI], 67.5%-75.4%), brodalumab (70.8%; 95% CrI, 66.8%-74.6%), ixekizumab (70.6%; 95% CrI, 66.8%-74.6%), and guselkumab (67.3%; 62.5%-71.9%). At weeks 44 to 60, the treatments with the highest PASI 90 rates were risankizumab-rzaa (79.4%, 95% CI, 75.5%-82.9%), guselkumab (76.5%; 95% CI, 72.1%-80.5%), brodalumab (74.0%; 95% CI, 69.3%-78.1%), and ixekizumab (73.9%; 95% CI, 69.9%-77.5%). Findings were consistent for short-term and long-term PASI 75 and 100 responses.Conclusions and relevanceThis study provides an assessment of the comparative efficacy among treatments for moderate to severe plaque psoriasis. The meta-analysis suggests that brodalumab, guselkumab, ixekizumab, and risankizumab-rzaa were associated with the highest PASI response rates in both short-term and long-term therapy.

Project description:Importance: Nail involvement is a common condition in patients with psoriasis. The treatment of nail psoriasis is considered challenging and is often left untreated by physicians. Objective: To assess the efficacy of current systemic treatments on nail psoriasis. Data Sources: PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for relevant articles from inception to September 1, 2020. Included articles were restricted to English language and human studies. Study Selection: This was a systematic literature review with meta-analysis. Thirty-five random control trials that evaluated systemic therapies for nail psoriasis were selected in the systemic review. Among them, we retained 14 trials for meta-analysis. Data Extraction and Synthesis: This study was conducted in accordance with the preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. All steps were performed by two independent investigators, and any disagreements were resolved by a third investigator. Meta-analysis of aggregated study data was conducted to assess therapeutic efficacy. The use of random-effects model was based on high heterogeneity as a variable endpoint in different studies. Main Outcomes and Measures: Therapeutic effects on nail psoriasis were expressed in terms of effect sizes with 95% CIs. Results: We included 35 random control trials (RCTs) in this systemic review. At baseline, a high prevalence (62.1%) of nail psoriasis was confirmed. The meta-analysis included 14 trials highlighting that biologic and small-molecule therapies were effective in treating nail psoriasis with variable effect size magnitudes [-0.89 (-1.10, -0.68), I 2 = 84%]. In particular, tofacitinib and ixekizumab showed the most significant scale of effect size magnitudes in treating nail psoriasis (-1.08 points and -0.93 points, respectively). We also found that a higher dose of tofacitinib and ixekizumab had similar effectiveness, and anti-IL-17 agents seem to be superior in effectiveness compared to anti-TNF-α therapies in the treatment of nail psoriasis. However, these results must be displayed carefully as variable endpoints in different studies. Conclusions and Relevance: This study provides a comprehensive overview of systemic treatments for nail psoriasis. For patients with psoriatic nail damage who are candidates of systemic therapies, the priority should be given to administering biologic and small-molecule therapies, especially anti-IL-17 drugs.

Project description:Psoriasis affects 1-3% of the population, in some people causing changes to the nails and joints in addition to skin lesions. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of systemic drug treatments, topical drug treatments, and non-drug treatments (other than ultraviolet light) for chronic plaque psoriasis? What are the effects of ultraviolet light treatments for chronic plaque psoriasis? What are the effects of combined treatment with drugs plus ultraviolet light on chronic plaque psoriasis? What are the effects of combined systemic plus topical drug treatments for chronic plaque psoriasis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2007 (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). We found 122 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupuncture, adding calcipotriol (topical) to psoralen plus ultraviolet light A or ultraviolet light B, adding oral retinoids to psoralen plus ultraviolet A (PUVA), alefacept, balneotherapy, ciclosporin, dithranol, T cell-targeted therapies, cytokine blocking agents, emollients (alone or plus ultraviolet light B), etanercept, fish oil supplementation, fumaric acid derivatives, Goeckerman treatment, heliotherapy, infliximab, Ingram regimen, keratolytics (salicylic acid, urea), leflunomide, methotrexate, oral pimecrolimus, phototherapy plus balneotherapy, psoralen plus ultraviolet A, psychotherapy, oral retinoids (alone or with ultraviolet light B), systemic drug treatments plus topical vitamin D derivatives, tars, tazarotene, topical corticosteroids (alone or plus oral retinoids), topical Vitamin D derivatives, ultraviolet light A, and ultraviolet light B.

Project description:BACKGROUND:To provide evidence for medical management of chronic idiopathic constipation (CIC) in China based on comparisons of all clinical practical interventions using Bayesian network meta-analysis. METHODS:We conducted a systematic literature review by searching PubMed, Embase, Cochrane Central, the China National Knowledge Infrastructure (CNKI), and the Wanfang Database (inception to May 2019) for randomized controlled trials (RCTs) for CIC in Chinese people. Only RCTs that recruited participants aged over 18 and diagnosed with CIC by the Rome II, III or IV criteria were included. We used three outcomes to examine efficacy. The risk ratio (RR) of the responder rate, based on ?3 spontaneous bowel movements (SBMs) per week after treatment, was the primary outcome, and the SBM count per week and the Bristol score (BS) were secondary outcomes. In addition, adverse effects (AEs) were also considered a secondary outcome to evaluate safety. We conducted Bayesian network meta-analysis with random effects, and the RR or mean difference with its 95% credible interval was calculated. In addition, we ranked all treatments via their cumulative curves (SUCRA) and assessed the quality of evidence according to the GRADE criteria. RESULTS:We included a total of 42 trials (6820 participants) of 20 grouped interventions that included pharmacological and nonpharmacological treatments. For the primary outcome, fourteen interventions were significantly better than placebo, and Probiotics plus Mosapride (PB?+?MP) appeared superior to others (GRADE quality of evidence: Moderate to Low), followed by Prucalopride (PP) (High to Low) and Electroacupuncture (EA) (High to Low). For SBM, Compound sodium bicarbonate suppository (CSBS) appeared to be best, with an SUCRA value of 90% (High to Low). For BS, Lactulose plus Probiotics (LT?+?PB) was superior to others (Moderate to Low), followed by Polyethylene glycol (PEG) (High to Moderate). Although all interventions appeared non-significant when compared with placebo in terms of adverse effects, Lactulose plus Mosapride showed greater risk than others on ranking probability. CONCLUSIONS:Given the GRADE assessment, PB?+?MP, PP and EA may be the priory options with moderate certainty in the quality of evidence for the primary outcome. For SBM, a CSBS may be the best option with moderate certainty in the quality of evidence. For BS, PEG may be the priory option with high certainty in the quality of evidence. However, due to a lack of high certainty in the quality of evidence, caution is needed when recommending the interventions. Because of the limitations, an increased number of trials are required for more accurate results.

Project description:ImportanceIncidence of neonatal abstinence syndrome is rising rapidly, and optimal pharmacotherapy may meaningfully reduce length of treatment.ObjectiveTo compare pharmacological therapies for neonatal abstinence syndrome.Data sourcesSystematic review and network meta-analysis of Medline (1946-June 2018), Embase (1974-June 2018), Cochrane CENTRAL (1966-June 2018), Web of Science (1900-June 2018), and ClinicalTrials.gov (June 2018).Study selectionRandomized clinical trials of pharmacological treatments for neonatal abstinence syndrome alone or in combination with adjuvant treatments. Abstract, title, and full-text screening were conducted independently by 2 reviewers (T.D. and C.G.).Data extraction and synthesisData extraction was conducted independently by 2 reviewers (T.D. and C.G.) according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-Network Meta-Analyses guidelines. Quality was assessed with the Cochrane Risk of Bias tool and data were pooled with fixed-effect models as a result of the low number of trials that were included in the analysis.Main outcomes and measuresThe primary outcome was the length of treatment. The length of stay, need for adjuvant therapy, and adverse events were considered as secondary outcomes.ResultsEighteen trials (N?=?1072) were eligible for inclusion. The treatments that were included in the length of treatment analysis were buprenorphine, clonidine, diluted tincture of opium and clonidine, diluted tincture of opium, morphine, methadone, and phenobarbital. Sublingual buprenorphine was considered the optimal treatment for a reduction in the length of treatment (days: mean difference vs morphine, -12.75 [95% CI, -17.97 to -7.58]; median rank, 1 [3-1]) and length of stay (days: mean difference vs morphine, -11.43 [95% CI, -16.95 to -5.82]; median rank, 1 [3-1]) but not the need for adjuvant treatment (odds ratio vs morphine, 1.23 [95% CI, 0.46-3.44]; median rank, 3 [5-1]). The results were robust to bias but sensitive to imprecision.Conclusions and relevanceThe current evidence suggests that buprenorphine is the optimal treatment for neonatal abstinence treatment, but limitations are considerable and wide-scale adoption requires a large multisite trial. Morphine, which is considered standard of care in most hospitals, was the lowest-ranked opioid for length of treatment and length of stay.

Project description:IntroductionRapid improvement of psoriasis is valued by patients and should be considered to be an important factor in treatment selection. We investigated Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) response rates within the first 12 weeks of treatment to compare the rapid response of 11 biologic therapies for moderate-to-severe psoriasis using Bayesian and Frequentist network meta-analyses (NMA).MethodsA systematic literature review was conducted to identify phase 3, double-blind, randomized, controlled trials for adult patients with moderate-to-severe psoriasis treated with interleukin (IL)-17 (brodalumab, ixekizumab, secukinumab), IL-12/-23 (ustekinumab), IL-23 (guselkumab, risankizumab, tildrakizumab), or tumor necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, infliximab). Outcome measures extracted from 32 publications were ≥ 75, ≥ 90, or 100% improvement in PASI score (PASI 75, PASI 90, or PASI 100, respectively) at weeks 2, 4, 8, and 12 and DLQI (0,1), where score (0,1) indicates no effect on patient's life, at week 12. Bayesian NMA (BNMA) used fixed-treatment effect and random-baseline effect, normal independent models. Frequentist NMA (fNMA) was conducted as sensitivity analyses to test the robustness of the findings.ResultsBased on BNMA and fNMA, brodalumab and ixekizumab showed the most rapid treatment effects on PASI 75 at weeks 2, 4, and 8 and on PASI 90 and PASI 100 at weeks 2, 4, 8, and 12; ixekizumab overlapped with risankizumab on PASI 75 at week 12. Brodalumab, ixekizumab, and secukinumab yielded higher DLQI (0,1) gains at week 12 compared to all of the other biologics studied. Additional measures of quality of life were not assessed in this report.ConclusionsIxekizumab and brodalumab provide the most rapid response and earliest clinical benefit at week 2 among all of the biologics studied, including other biologic treatments such as secukinumab, ustekinumab, guselkumab, adalimumab, and etanercept. BNMA and fNMA results showed similar relative effect estimates and treatment rankings.FundingEli Lilly and Company.

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Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.

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