Indirect Treatment Comparison Meta-analysis Research Articles

Acupuncture versus tricyclic antidepressants in the prophylactic treatment of tension-type headaches: an indirect treatment comparison meta-analysis

BackgroundAcupuncture showed better improvement than sham acupuncture in reducing attack frequency of tension-type headache (TTH), but its effectiveness relative to first-line drugs for TTH is unknown, which impedes the recommendation of acupuncture for patients who are intolerant to drugs for TTH. We aimed to estimate the relative effectiveness between acupuncture and tricyclic antidepressants (TCAs) through indirect treatment comparison (ITC) meta-analysis.MethodsWe searched Ovid Medline, Embase, and Cochrane Library from database inception until April 13, 2023. Randomized controlled trials of TCAs or acupuncture in the prevention of TTH in adults were included. The primary outcome was headache frequency. The secondary outcomes were headache intensity, responder rate, and adverse event rate. Bayesian random-effect models were used to perform ITC meta-analysis, and confidence of evidence was evaluated by using the GRADE approach.ResultsA total of 34 trials involving 4426 participants were included. Acupuncture had similar effect with TCAs in decreasing TTH frequency (amitriptyline: mean difference [MD] -1.29, 95% CI -5.28 to 3.02; amitriptylinoxide: MD -0.05, 95% CI -6.86 to 7.06) and reducing TTH intensity (amitriptyline: MD 2.35, 95% CI -1.20 to 5.78; clomipramine: MD 1.83, 95% CI -4.23 to 8.20). Amitriptyline had a higher rate of adverse events than acupuncture (OR 4.73, 95% CI 1.42 to 14.23).ConclusionAcupuncture had similar effect as TCAs in reducing headache frequency of TTH, and acupuncture had a lower adverse events rate than amitriptyline, as shown by very low certainty of evidence.

Eluxadoline Versus Antispasmodics in the Treatment of Irritable Bowel Syndrome: An Adjusted Indirect Treatment Comparison Meta-analysis.

Objective: Eluxadoline is a newly approved drug for irritable bowel syndrome (IBS), but it has rarely been compared with positive controls. We aimed to compare eluxadoline with antispasmodics in the treatment of IBS. Methods: We searched the OVID Medline, Embase, and the Cochrane Central Register of Controlled Trials databases for randomized controlled trials (RCTs) comparing eluxadoline or antispasmodics with placebo. The search was conducted from 1 January 1980, to 1 September 2020, without any language restrictions. The primary efficacy outcome was the relief of abdominal pain, defined by a reduction of pain scores of at least 30% from baseline. The secondary efficacy outcome was the relief of global IBS symptoms, defined by a composite response of a decrease in abdominal pain and improvement in stool consistency on the same day for at least 50% of the days assessed. The data were pooled using a random-effects model. Outcome estimates were pooled by using Risk Ratios (RRs) and P-scores. Results: Forty-two trials with 8,457 participants were included from 45 articles. Compared with placebo, each of drotaverine, pinaverium, alverine combined with simethicone (ACS) and eluxadoline 100 mg was highly effective in the relief of abdominal pain, with drotaverine [RR, 2.71 (95% CI, 1.70 to 4.32), P-score = 0.95] ranking first. Drotaverine, otilonium, cimetropium, pinaverium, and eluxadoline 100 mg had significantly high the relief of global IBS symptomss, for which drotaverine [RR, 2.45 (95% CI, 1.42 to 4.22), P-score = 0.95] was ranked first. No significant difference was found between these interventions. Pinaverium had a significantly higher the relief of global IBS symptoms than eluxadoline [RR, 1.72 (95% CI, 1.33 to 2.21)] on sensitivity analysis. However, no significant difference was found in the number of adverse events between each intervention and the placebo. Conclusion: Our network meta-analysis showed that eluxadoline 100 mg was at least as effective as antispasmodics in relieving abdominal pain in IBS. But eluxadoline had more reported adverse events. Antispasmodics are still the first choice for the treatment of IBS.

Indirect treatment comparison of solriamfetol, modafinil, and armodafinil for excessive daytime sleepiness in obstructive sleep apnea.

Excessive daytime sleepiness associated with obstructive sleep apnea affects 9%-22% of continuous positive airway pressure-treated patients. An indirect treatment comparison meta-analysis was performed to compare efficacy and safety of medications (solriamfetol, modafinil, and armodafinil) approved to treat excessive daytime sleepiness associated with obstructive sleep apnea. Efficacy and safety measures assessed in this indirect treatment comparison included Epworth Sleepiness Scale (ESS), 20-minute Maintenance of Wakefulness Test (MWT20), Clinical Global Impression of Change (CGI-C), Functional Outcomes of Sleep Questionnaire (FOSQ), and incidence of treatment-emergent adverse events (any, serious, or leading to discontinuation). A systematic literature review identified 6 parallel-arm, placebo-controlled randomized controlled trials that randomized 1,714 total participants to placebo, solriamfetol, modafinil, or armodafinil. In this indirect treatment comparison, all comparators were associated with greater improvements than placebo on the ESS, MWT20, and CGI-C after 4, 8, and 12 weeks of treatment. Relative to comparators and placebo at 12 weeks, solriamfetol at 150 mg or 300 mg had the highest probabilities of improvement in the ESS, MWT20, and CGI-C. Modafinil (200 or 400 mg) and solriamfetol (150 or 300 mg) were associated with greater improvement on the FOSQ than placebo at 12 weeks. Less than 2% of patients using placebo or comparators experienced serious or discontinuation-related treatment-emergent adverse events. The results of this indirect treatment comparison show 12 weeks of treatment with solriamfetol, modafinil, and armodafinil resulted in varying levels of improvement on the ESS, MWT20, and CGI-C and similar safety risks in participants with excessive daytime sleepiness associated with obstructive sleep apnea. Ronnebaum S, Bron M, Patel D, etal. Indirect treatment comparison of solriamfetol, modafinil, and armodafinil for excessive daytime sleepiness in obstructive sleep apnea. J Clin Sleep Med. 2021;17(12):2543-2555.

Calcitonin Gene-Related Peptide Monoclonal Antibodies Versus Botulinum Neurotoxin a in the Preventive Treatment of Chronic Migraine: An Adjusted Indirect Treatment Comparison Meta-Analysis.

Purpose: Calcitonin gene-related peptide monoclonal antibodies (CGRPmAbs) are new agents approved by the US Food and Drug Administration for preventive treatment of chronic migraine. Comparison between CGRPmAbs and previously approved Botulinum neurotoxin A (BoNT-A) will inform optimal preventive treatment of chronic migraine, but head-to-head trials are lacking. We therefore aimed to perform adjusted indirect comparison between CGRPmAbs and BoNT-A through a meta-analysis. Methods: OVID MEDLINE, EMBASE and the Cochrane central register of controlled trials, clinical registries, and government websites were searched from inception to September 2019. Randomized controlled trials comparing CGRPmAbs or BoNT-A with placebo in the preventive treatment of chronic migraine were included. The primary outcomes were headache days and migraine days measured at week 12. Data were synthesized by using a frequentist approach; and the treatments were ranked by P-score. Results: We included 10 trials (n = 4,678) after screening 1049 candidates. Six trials were with low risk of bias. Fremanezumab had an effect similar to BoNT-A in the reduction of headache days at week 12 (standard mean difference [SMD] 0.08, 95%CI -0.55 to -0.7). Galcanezumab reduced more migraine days than BoNT-A at week 12 (SMD, -0.94, 95%CI −1.24 to −0.63); fremanezumab showed similar findings (SMD, −0.55, 95%CI −0.85 to −0.24). Galcanezumab and fremanezumab had better effect in mitigating headache impact at week 12. CGRPmAbs and BoNT-A had similar adverse event rate. Conclusion: CGRPmAbs and BoNT-A had similar effect in the preventive treatment of chronic migraine. BoNT-A might be preferentially selected owing to its cost-effectiveness profiles. Further studies with direct comparison of the two treatments are warranted.

Causal inference and adjustment for reference-arm risk in indirect treatment comparison meta-analysis.

Aim: To illustrate that bias associated with indirect treatment comparison and network meta-analyses can be reduced by adjusting for outcomes on common reference arms. Materials & methods: Approaches to adjusting for reference-arm effects are presented within a causal inference framework. Bayesian and Frequentist approaches are applied to three real data examples. Results: Reference-arm adjustment can significantly impact estimated treatment differences, improve model fit and align indirectly estimated treatment effects with those observed in randomized trials. Reference-arm adjustment can possibly reverse the direction of estimated treatment effects. Conclusion: Accumulating theoretical and empirical evidence underscores the importance of adjusting for reference-arm outcomes in indirect treatment comparison and network meta-analyses to make full use of data and reduce the risk of bias in estimated treatments effects.

Once-daily liraglutide (1.2 mg) compared with twice-daily exenatide (10 μg) in the treatment of type 2 diabetes patients: An indirect treatment comparison meta-analysis.

Glucagon-like peptide-1 receptor agonists provide effective hyperglycemia management in patients with type 2 diabetes. In a randomized head-to-head trial, liraglutide 1.8 mg q.d. led to greater reductions in HbA1c than exenatide 10 μg b.i.d. There are no direct comparisons of liraglutide 1.2 mg q.d. and exenatide b.i.d.; therefore, in the present study, an indirect comparison and meta-analysis were undertaken. A systematic literature search was performed for randomized controlled trials of liraglutide 1.2 mg q.d. or exenatide b.i.d. with HbA1c as an outcome and ≥25 subjects. Key data were extracted and analyzed. A random-effects model was used to incorporate heterogeneity between studies. Three liraglutide 1.2 mg q.d. (n = 1060) and 10 exenatide b.i.d. (n = 2609) placebo-controlled studies were identified, allowing indirect comparison with placebo as the common arm. Baseline characteristics were mean age ~55 years, disease duration ~7 years, HbA1c ~8%, and body mass index ~32 kg/m2 . Compared with exenatide b.i.d., liraglutide 1.2 mg was associated with significantly greater reductions from baseline in HbA1c (-0.29%; 95% confidence interval [CI] -0.53, -0.05) and fasting plasma glucose (-0.92 mmol/L; 95% CI -1.43, -0.41), with shorter duration of nausea (3 vs 14 days; P = 0.002) and fewer withdrawals (odds ratio 0.34; 95% CI 0.22, 0.52). The incidence of adverse events (including nausea) and withdrawals because of adverse events were similar between treatments. Liraglutide 1.2 mg provided a significantly greater reduction in HbA1c than exenatide 10 μg b.i.d. The significantly shorter duration of nausea with liraglutide than exenatide may be appreciated by patients.

Comparative efficacy and safety of estradiol transdermal preparations for the treatment of vasomotor symptoms in postmenopausal women

Divigel and Estrogel are estradiol gels for the treatment of postmenopausal women with moderate to severe vasomotor symptoms. They differ with respect to several factors including estradiol concentration and surface application, and cannot be compared solely on the basis of their estradiol dose. No randomized clinical trials have compared them head to head, but both have been compared with placebo. Therefore, the objective of this study was to conduct a systematic review and network meta-analysis of the two estradiol gels. We performed a comprehensive systematic literature review. One publication reporting on one Divigel trial, three publications reporting on two Estrogel trials, and five publications reporting on other estradiol transdermal preparations were identified. Efficacy outcomes were change from baseline in daily hot flush frequency and change from baseline in daily hot flush severity. Safety outcomes were frequency of treatment-related adverse events (AEs) and frequency of treatment-emergent AEs leading to discontinuation. Bayesian indirect treatment comparison meta-analysis of trial-level data was performed in accordance with the International Society for Pharmacoeconomics and Outcomes Research, Academy of Managed Care Pharmacy, National Pharmaceutical Council (ISPOR-AMCP-NPC) Good Practice Questionnaire. All outcomes were compared with respect to doses of the considered preparations. For hot flush frequency, Divigel 0.25 mg was similar to Divigel 0.5 mg and to Estrogel 0.75 mg, and was statistically significantly superior to Estrogel 1.5 mg. The largest effect was observed with Divigel 1.0 mg (mean difference of 3.91 hot flushes/wk vs placebo), and was statistically significantly superior to all other interventions. The 1.5 mg Estrogel dose was associated with the smallest estimate of efficacy. For hot flush severity, Divigel 0.25 mg was similar to the efficacy of Divigel 0.5 mg, and for 0.25 mg and 0.5 mg of other estradiol gels, but was statistically inferior to Divigel 1.0 mg, Estrogel 0.75 mg, Estrogel 1.5 mg, and the 1.0 and 1.5 mg doses of all other estradiol gels. The estimated efficacy of Divigel 0.5 mg was similar to that of Estrogel 0.75 mg, Estrogel 1.5 mg, and the 0.25 and 0.5 mg doses of other transdermal estradiol preparations. Risks of treatment-related AEs for Divigel 0.25 mg, Divigel 0.5 mg, Estrogel 0.75 mg, and Estrogel 1.5 mg were similar and all were of a slightly higher risk than placebo. Among these, Divigel 1.0 mg, Estrogel 1.5 mg, and other gels 0.5 mg were statistically significantly less safe than placebo. However, for treatment-emergent AEs leading to discontinuation, none of the gels were associated with statistically significantly higher relative risks compared with placebo. In this study, statistically significant refers to the 95% credible intervals used in the Bayesian Network Analysis. Using network meta-analysis for indirect treatment comparison, we have shown that the efficacy of Divigel 0.25 mg, as measured by reduced hot flush frequency and severity, was similar to that of Divigel 0.5 mg and of Estrogel 0.75 and 1.5 mg. Overall, our analysis showed that Divigel 1.0 mg provided the best efficacy profile, but that this treatment was also associated with a higher risk of AEs. The network meta-analysis also showed that treatment with Estrogel 1.5 mg was associated with the smallest estimate of reduction in frequency of hot flushes.

The efficacy and safety of different anticoagulants on patients with severe sepsis and derangement of coagulation: a protocol for network meta-analysis of randomised controlled trials

IntroductionSepsis is the leading cause of mortality in non-cardiological critically ill patients. There are as many as 20 million cases of sepsis annually worldwide, with a mortality rate of around...

Uterine-sparing minimally invasive interventions in women with uterine fibroids: a systematic review and indirect treatment comparison meta-analysis.

To evaluate the effectiveness of uterine-sparing interventions for women with symptomatic uterine fibroids who wish to preserve their uterus. Systematic review and indirect comparison meta-analysis. MEDLINE, EMBASE, CENTRAL, conference proceedings, trial registers and reference lists were searched up to October 2013 for randomized controlled trials. Outcome measures were patient satisfaction, re-intervention and complications rates, reproductive outcomes, and hospitalization and recovery times. Five trials, involving 436 women were included; two compared uterine artery embolization with myomectomy and three compared uterine artery embolization with laparoscopic uterine artery occlusion. Indirect treatment comparison showed that myomectomy and uterine artery embolization resulted in higher rates of patient satisfaction (odds ratio 2.56, 95% credible interval 0.56-11.75 and 2.7, 95% credible interval 1.1-7.14, respectively) and lower rates of clinical failure (odds ratio 0.29, 95% credible interval 0.06-1.46 and 0.37, 95% credible interval 0.13-0.93, respectively) than laparoscopic uterine artery occlusion. Myomectomy resulted in lower re-intervention rate than uterine artery embolization (odds ratio 0.08, 95% credible interval 0.02-0.27) and laparoscopic uterine artery occlusion (odds ratio 0.08, 95% credible interval 0.01-0.37) even though the latter techniques had an advantage over myomectomy because of shorter hospitalization and quicker recovery. There was no evidence of difference between the three techniques in ovarian failure and complications rates. The evidence for reproductive outcomes is poor. Our study's results suggest that laparoscopic uterine artery occlusion is less effective than uterine artery embolization and myomectomy in treatment of symptomatic fibroids. The choice between uterine artery embolization and myomectomy should be based on individuals' expectations and fully informed discussion.

PGI1 - Comparative efficacy and safety of golimumab, infliximab and adalimumab for the treatment of moderate to severe ulcerative colitis: A bayesian indirect treatment comparison meta-analysis

To compare the relative efficacy and safety of golimumab, infliximab and adalimumab for the treatment of moderate-to-severe ulcerative colitis using indirect treatment comparison (ITC) meta-analysis. A systematic literature search identified five randomized controlled trials. Outcomes of interest included clinical remission, clinical response, mucosal healing, sustained remission/response, serious adverse events (SAEs), and discontinuation due to adverse events (DAEs). Data was synthesized using Bayesian indirect treatment comparison (ITC) meta-analysis. The analysis incorporated advanced intention-to-treat with baseline priors to account for the alternative design of the golimumab trial. After the induction phase, each treatment had significantly greater efficacy than placebo all endpoints, with the exception of adalimumab for mucosal healing. No statistical differences were observed between golimumab and infliximab. Adalimumab had significantly lower efficacy measures compared to infliximab for clinical remission (odds ratio [OR] 0.42, 95% credible interval [CrI] 0.17-0.97), clinical response (OR 0.45, 95% CrI 0.23-0.89), and mucosal healing (OR 0.46, 95% CrI 0.25-0.84) after the induction period. During the maintenance phase, each biologic agent exhibited significantly greater efficacy compared to placebo for clinical remission, clinical response, and mucosal healing. Golimumab 100mg was significantly better than adalimumab for clinical response (OR 1.80, 95% CrI 1.01-3.21) and mucosal healing at 54 weeks (OR 1.88, 95% CrI 1.01-3.49). No statistical differences were observed between adalimumab and infliximab. Both golimumab 100mg and infliximab were significantly better than adalimumab in terms of sustained clinical response (OR 2.40, 95% CrI 1.17-4.86 and OR 1.93, 95% CrI 1.04-4.06), respectively. For SAEs, there were no statistical differences between any of the biologics and placebo. Although all biologics were generally safe, golimumab 100mg had statistically significantly higher DAEs when compared to adalimumab (OR 2.09, 95% CrI 1.07-4.17). In the context of ITC meta-analysis, both golimumab and infliximab appear to demonstrate superior efficacy-safety profiles compared with adalimumab.

Su1134 Comparative Efficacy of Biologic Therapy in the Management of Biologic-Naive Patients With Ulcerative Colitis: An Indirect Treatment Comparison Meta-Analysis

S-384 AGA Abstracts are primarily driven by insurance coverage and patient preference. In the absence of headto-head clinical trials, we sought to estimate the comparative efficacy of biologic therapy in the management of biologic-Naive patients with UC through an indirect treatment comparison networkmeta-analysis of randomized controlled trials (RCTs).Methods: Through a systematic search of multiple databases through September 2013, we identified RCTs in adults with UC comparing biologic therapy (infliximab [IFX], adalimumab [ADA], golimumab [GLM] and vedolizumab [VEDO]) to each other or placebo, in inducing and maintaining clinical remission in UC. We extracted data on efficacy in a subset of biologic-Naive patients to allow a homogenous comparison. We conducted traditional random effect meta-analyses to estimate the direct effect and then conducted network meta-analysis to combine direct and indirect estimates, expressed as odds ratio (OR) with 95% confidence intervals (CI). Results: We identified 9 clinical trials assessing efficacy of biologic therapy in inducing remission in UC, with all trials comparing treatment against only placebo. On direct comparison, both anti-TNF agents and VEDO were more effective than placebo. On indirect comparison, no single agent was superior to others. Although patients on IFX were almost twice as likely to achieve induction of remission than those on ADA (IFX v. ADA: OR, 1.9; 95% CI, 0.84.6), this difference was not statistically significant (p=0.17). Similarly, patients on ADA were 40% less likely to achieve induction of clinical remission than those on GLM (ADA v. GLM: OR, 0.6; 95% CI, 0.3-1.2), but this difference was also not statistically significant (p=0.18) (Table 1). A non-significant trend was observed suggesting that IFX may be more efficacious than ADA in inducing mucosal healing (IFX v. ADA: OR, 2.0; 95% CI, 0.974.3, p=0.06) IFX appeared superior to ADA, GLM and VEDO in maintaining remission (and maintaining mucosal healing) in patients with UC; however, due to differences in trial design, comparability was limited (Table 2). Conclusions: Based on indirect treatment comparison, IFX, ADA, GLM and VEDO had comparable efficacy, with no agent being clearly superior to others. There was a non-significant trend suggesting that IFX may be superior to ADA in inducing mucosal healing in anti-TNF Naive patients with UC. However, in the absence of head-to-head treatment comparison, confidence in these estimates is low. Future head-to-head treatment comparison trails and comparative effectiveness observational studies in a homogenous cohort are warranted. Comparative Efficacy of Biologic Therapy in Inducing Remission in UC

The Efficacy and Safety of Different Kinds of Laparoscopic Cholecystectomy: A Network Meta Analysis of 43 Randomized Controlled Trials

Background and ObjectiveWe conducted a network meta analysis (NMA) to compare different kinds of laparoscopic cholecystectomy [LC] (single port [SPLC], two ports [2PLC], three ports [3PLC], and four ports laparoscopic cholecystectomy [4PLC], and four ports mini-laparoscopic cholecystectomy [mini-4PLC]).MethodsPubMed, the Cochrane library, EMBASE, and ISI Web of Knowledge were searched to find randomized controlled trials [RCTs]. Direct pair-wise meta analysis (DMA), indirect treatment comparison meta analysis (ITC) and NMA were conducted to compare different kinds of LC.ResultsWe included 43 RCTs. The risk of bias of included studies was high. DMA showed that SPLC was associated with more postoperative complications, longer operative time, and higher cosmetic score than 4PLC, longer operative time and higher cosmetic score than 3PLC, more postoperative complications than mini-4PLC. Mini-4PLC was associated with longer operative time than 4PLC. ITC showed that 3PLC was associated with shorter operative time than mini-4PLC, and lower postoperative pain level than 2PLC. 2PLC was associated with fewer postoperative complications and longer hospital stay than SPLC. NMA showed that SPLC was associated with more postoperative complications than mini-4PLC, and longer operative time than 4PLC.ConclusionThe rank probability plot suggested 4PLC might be the worst due to the highest level of postoperative pain, longest hospital stay, and lowest level of cosmetic score. The best one might be mini-4PLC because of highest level of cosmetic score, and fewest postoperative complications, or SPLC because of lowest level of postoperative pain and shortest hospital stay. But more studies are needed to determine which will be better between mini-4PLC and SPLC.

Effectiveness of Valganciclovir 900 mg versus 450 mg for Cytomegalovirus Prophylaxis in Transplantation: Direct and Indirect Treatment Comparison Meta-analysis

valganciclovir (VGC) 900 mg is approved for CMV prophylaxis, but it has been associated with 10%-40% leucopenia rate. We hypothesize that VGC 450 mg daily may be as effective as and safer than 900 mg daily. studies evaluating valganciclovir 900 mg and 450 mg daily against controls were evaluated. Direct comparisons were performed by random-effects models and indirect comparisons by the Bucher method. twelve trials with VGC 900 mg (1543 patients) and 8 trials with VGC 450 mg (1531 patients) were included. The risk of CMV disease with VGC 900 mg versus controls was 1.06 (95% confidence interval [CI], .64-1.76; P = .81; I2=29%) and with VGC 450 mg vs controls .77 (95%CI, .49-1.18; P = .23; I2=24%). The risk of leucopenia was 5.24 (2.09-13.15; P = .0004; I2=44%) for VGC 900 mg versus controls and 1.58 (.96-2.61; P = .07; I2=36%) for VGC 450 mg versus controls; the risk for acute allograft rejection was 1.71 (.45, -6.50; P = .43) for VGC 900 mg and .80 (.50-1.28; P = .34) for VGC 450 mg. Adjusted indirect comparison between VGC 900 mg and VGC 450mg: the risk for CMV disease was not significantly different: odds ratio (OR), 1.38 (.84-2.25); P = .19; the risk of leucopenia was significantly increased with VGC 900 mg: 3.32 (1.76-6.26); P = .0002; and the risk of rejection was significantly increased with VGC 900 mg: 2.56 (1.50-4.53); P = .0005. Results remained consistent after adjustments by allograft, CMV control strategy, and immunosuppression. valganciclovir 900 mg showed no superiority efficacy compared to controls (ganciclovir or preemptive) and equivalent efficacy to VGC 450 mg (statistical power: 94% and 97%, respectively) for CMV universal prophylaxis.VGC 900 mg was significantly associated with 3 times increase in the risk of leucopenia and 2 times increase in the risk of rejection compared with VGC 450 mg.