Cost-effectiveness of eculizumab and efgartigimod for the treatment of anti-acetylcholine receptor antibody-positive generalized myasthenia gravis.

BACKGROUND: Eculizumab and efgartigimod were approved to treat anti-acetylcholine receptor antibody-positive generalized myasthenia gravis (anti-AChR Ab-positive gMG). These relatively new biological treatments provide a more rapid onset of action and improved efficacy compared with conventional immunosuppressive treatments, but at a higher cost. OBJECTIVE: To assess the cost-effectiveness of eculizumab and, separately, efgartigimod, each added to conventional therapy vs conventional therapy alone, among patients with refractory anti-AChR Ab-positive gMG and those with anti-AChR Ab-positive gMG, respectively. METHODS: A Markov model with 4 health states was developed, evaluating costs and utility with a 4-week cycle length and lifetime time horizon from a health care system perspective and a modified societal perspective including productivity losses from patients and caregiver burden. Model inputs were informed by key clinical trials and relevant publications identified from targeted literature reviews, and drug costs were identified from Micromedex Red Book. Costs and outcomes were discounted at 3% per year. Incremental cost-effectiveness ratios (ICERs; cost per quality-adjusted life-year [QALY] gained) were calculated for each comparison. RESULTS: Among the corresponding populations, lifetime costs and QALYs, respectively, for eculizumab were $5,515,000 and 11.85, and for conventional therapy, $308,000 and 10.29, resulting in an ICER of $3,338,000/QALY gained. For efgartigimod, lifetime costs and QALYs, respectively, were $6,773,000 and 13.22, and for conventional therapy, $322,000 and 9.98, yielding an ICER of $1,987,000/QALY gained. After applying indirect costs in a modified societal perspective, the ICERs were reduced to $3,310,000/QALY gained for eculizumab and $1,959,000/QALY gained for efgartigimod. CONCLUSIONS: Eculizumab and efgartigimod are rapidly acting and effective treatments for myasthenia gravis. However, at their current price, both therapies greatly exceeded common cost-effectiveness thresholds, likely limiting patient access to these therapies.

Fanconi Syndrome in Patients With Human Immunodeficiency Virus Treated With Tenofovir-Based Antiretroviral Therapy: A Systematic Literature Review.

OBJECTIVE: Several cases of Fanconi syndrome (FS), a severe form of nephrotoxicity, have been reported in patients with HIV on tenofovir-containing antiretroviral therapy. A systematic review of the published literature on tenofovir-related FS in patients with HIV was conducted. DATA SOURCES: PubMed and Embase were queried to identify articles in English published between January 2005 and June 2023, reporting tenofovir-related FS in adults with HIV. Preclinical studies, conference/poster abstracts, commentaries and responses, and review papers were excluded. STUDY SELECTION AND DATA EXTRACTION: Of the 256 articles screened, 57 met the inclusion criteria. These comprised 37 case reports, 11 case series, 1 cross-sectional study, 1 case-control study, 4 cohort studies, 1 single-arm open-label clinical trial, 1 sub-analysis of clinical trials, and 1 pooled analysis of clinical trials. DATA SYNTHESIS: Among 56 cases on which information was abstracted, median age at FS diagnosis was 50 years, 51.8% were men, and duration of tenofovir use ranged from 6 weeks to 11 years. Ritonavir was co-prescribed in almost half the cases. In observational and interventional studies, incidence of FS was low. Many studies reported resolution of FS symptoms after tenofovir discontinuation. All FS occurrences were identified in those on tenofovir disoproxil fumarate (TDF), except for one patient on tenofovir alafenamide (TAF). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Continuous monitoring of signs and symptoms of renal and bone toxicity is essential for patients with HIV on tenofovir-containing therapy. CONCLUSIONS: Occurrence of FS is low in patients with HIV treated with tenofovir-based regimens. Concomitant use of ritonavir may increase risk of FS. TAF may be a safer alternative than TDF in terms of nephrotoxicity.

Cost-Effectiveness of Nadofaragene Firadenovec and Pembrolizumab in Bacillus Calmette-Guérin Immunotherapy Unresponsive Non-Muscle Invasive Bladder Cancer.

OBJECTIVES: Nadofaragene firadenovec is a gene therapy for bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) undergoing Food and Drug Administration review. Pembrolizumab is approved for treating patients with BCG-unresponsive NMIBC with carcinoma in situ (CIS). We evaluated the cost-effectiveness of these treatments compared with a hypothetical therapeutic alternative, at a willingness-to-pay threshold of $150 000 per quality-adjusted life-year (QALY) gained, in CIS and non-CIS BCG-unresponsive NMIBC populations. METHODS: We developed a Markov cohort simulation model with a 3-month cycle length and lifetime horizon to estimate the total costs, QALYs, and cost per additional QALY from the health sector perspective. Clinical inputs were informed by results of single-arm clinical trials evaluating the treatments, and systematic literature reviews were conducted to obtain other model inputs. Sensitivity analyses were conducted to assess uncertainty in model results. RESULTS: Nadofaragene firadenovec, at a placeholder price 10% higher than the price of pembrolizumab, had an incremental cost-effectiveness ratio of $263 000 and $145 000 per QALY gained in CIS and non-CIS populations, respectively. Pembrolizumab had an incremental cost-effectiveness ratio of $168 000 per QALY gained for CIS. A 5.4% reduction in pembrolizumab's price would make it cost-effective. The model was sensitive to many inputs, especially to the probabilities of disease progression, initial treatment response and durability, and drug price. CONCLUSIONS: The cost-effectiveness of nadofaragene firadenovec will depend upon its price. Pembrolizumab, although not cost-effective in our base-case analysis, is an important alternative in this population with an unmet medical need. Comparative trials of these treatments are warranted to better estimate cost-effectiveness.