Treatment Options for Management of Facial Angiofibroma Associated with Tuberous Sclerosis Complex: A Systematic Review of Evidence of Clinical Effectiveness and Cost-Effectiveness

Author(s)

John D1, Schachner LA2, Teng J3, Aman MS4, Paul Choudhury S1, Boggarapu S5, Beresford E5
1PharmaQuant Insights Pvt. Ltd., Kolkata, WB, India, 2University of Miami Miller School of Medicine, Miami, FL, USA, 3Lucile Packard Children’s Hospital, Stanford, CA, USA, 4PharmaQuant Insights Pvt. Ltd., Kolkata , WB, India, 5Nobelpharma America, LLC, Bethesda, MD, USA

OBJECTIVES: We conducted a systematic review to analyze clinical and cost-effectiveness evidence of treatment options for facial angiofibroma (FA) associated with tuberous sclerosis complex (TSC) which lacks established therapeutic opportunities.

METHODS: Multiple academic databases, HTA databases, trial registries, conferences, were searched (March-April 2022) for randomized controlled trials (RCTs), non-RCTs, observational and cost-effectiveness studies. Risk of bias, study quality, were assessed using standard checklists. Random effects meta-analysis was conducted using Residual Maximum Likelihood to compute study variances. Findings were reported using Synthesis Without Meta-analysis guidelines.

RESULTS: Of 12459 studies, 8155 and 401 were screened at title-abstract and full text, and 91 were included (6 RCTs, 7 non-RCTs, 78 observational). From 2491 cost-effectiveness studies, 48 underwent full-text screening; none were included. Topical sirolimus 0.1% was most frequently examined (2 RCTs, 1 non-RCTs, 8 observational), followed by sirolimus 0.2% (3 RCTs, 3 observational). Quantitative improvements, including change from baseline using angiofibroma grading scale, was reported in 1 RCT; FA severity index scores (FASI) showed improvement in 2 RCTs with topical sirolimus (0.05%,0.1%,0.2%); 6 cohort studies, 1 case-series and case-report each described post-treatment FASI score improvements with topical sirolimus/rapamycin (0.1%,0.2%,0.4%,1%,0.1%+1%). Pooled meta-analysis of 2 trials showed 63% response rate with topical sirolimus 0.2% gel compared with placebo. Patients with any treatment-emergent-adverse event (TEAE) ranged from 1.6%-62.5%, serious AEs from 3.33%-5.55%. Four trials reported recurrence following treatment cessation. Risk of bias was low (3 RCTs), some concerns (3 RCT), moderate (5 non-RCTs), and serious (2 non-RCTs). Among cohort studies, 4 were moderate, 3 low, and 8 of high quality. Most case-series and case-reports had >5 score (JBI checklists).

CONCLUSIONS: Topical sirolimus is a low risk, well-tolerated treatment. This first comprehensive review of clinical and cost-effectiveness evidence on treating FA associated with TSC may provide clinical guidance for therapeutic selections.

Conference/Value in Health Info

2023-05, ISPOR 2023, Boston, MA, USA

Value in Health, Volume 26, Issue 6, S2 (June 2023)

Code

CO217

Topic

Study Approaches

Topic Subcategory

Literature Review & Synthesis

Disease

Rare & Orphan Diseases

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