Cost-effectiveness of rimegepant oral lyophilisate compared to best supportive care for the acute treatment of migraine in the UK.

AIMS: Migraine is the most common disabling headache disorder and is characterized by recurrent throbbing head pain and symptoms of photophobia, phonophobia, nausea, and vomiting. Rimegepant 75 mg, an oral lyophilisate calcitonin gene-related peptide antagonist, is the first treatment approved for both the acute and preventative treatment of migraine, and the first acute therapy approved in over 20-years. The objective was to assess the cost-utility of rimegepant compared with best supportive care (BSC) in the UK, for the acute treatment of migraine in the adults with inadequate symptom relief after taking at least 2 triptans, or for whom triptans are contraindicated or not tolerated. MATERIALS AND METHODS: A de novo model was developed to estimate incremental costs and quality-adjusted life years (QALYs), structured as a decision tree followed by Markov model. Patients received rimegepant or BSC for a migraine attack and were assessed for response (pain relief at 2-h). Responders and non-responders followed different pain trajectories over 48-h cycles. Non-responders discontinued treatment while responders continued treatment for subsequent attacks, with a proportion discontinuing over time. Data sources included a post-hoc pooled analysis of the phase 3 acute rimegepant trials (NCT03235479, NCT03237845, NCT03461757), and a long-term safety study (NCT03266588). The analysis was conducted from the perspective of the UK National Health Service and Personal Social Services over a 20-year time horizon. RESULTS: Rimegepant resulted in an incremental cost-utility ratio (ICUR) of £10,309 per QALY gained vs BSC, which is cost-effectiveness at a willingness to pay threshold of £30,000/QALY. Rimegepant generated +0.44 incremental QALYs and higher incremental lifetime costs (£4,492). Improved QALYs for rimegepant were a result of less time spent with severe and moderate headache pain. CONCLUSION: This study highlights the economic value of rimegepant which was found to be cost-effective for the acute treatment of migraine in adults unsuitable for triptans.

Comparative Effectiveness of Tofacitinib and Adalimumab in Axial Spondyloarthritis: A Real-World Clinical Context Multicenter Study.

INTRODUCTION: Tofacitinib, an oral Janus kinase inhibitor, is a putative choice in the treatment of axial spondyloarthritis (AxSpA). The objective of this study was to compare the effectiveness and tolerability of tofacitinib with adalimumab, in AxSpA, in a real-world clinical setting. METHODS: In this multicentric medical records review study, adult patients with active AxSpA treated with either tofacitinib 5 mg twice daily or adalimumab 40 mg subcutaneously fortnightly were recruited. Effectiveness was measured with Ankylosing Spondylitis Disease Activity Score (ASDAS) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Drug-cost analysis was calculated with Incremental Cost-Effectiveness Ratio (ICER drug ). RESULTS: Among the 266 patients, 135 were treated with tofacitinib and 131 with adalimumab (follow-up: 6.5 ± 1.6 months). Mean improvement of BASDAI (3.39 ± 0.09 vs. 3.14 ± 1.16, respectively) and that of ASDAS (1.78 ± 0.68 vs. 2.07 ± 2.08, respectively) were comparable between the adalimumab and tofacitinib groups. A higher proportion of patients achieved BASDAI50 response in the second (49.5% vs. 31.6%) and fourth month (83.9% vs. 62.8%) and ASDAS low disease activity in the fourth month (71.6% vs. 47.9%) in the adalimumab group. All disease activity measurements were similar by the sixth month in both groups. A higher proportion of patients in the tofacitinib group than in the adalimumab group required change in therapy (14.8% vs. 7.6%, respectively). ICER drug for adalimumab compared with tofacitinib was US $188.8 per patient in the adalimumab group for each person-month with BASDAI <4. CONCLUSIONS: Tofacitinib showed comparable effectiveness with adalimumab in patients with AxSpA at the sixth month, despite lesser response in the initial months, with favorable ICER drug .

Assessment of Alectinib vs Ceritinib in ALK-Positive Non-Small Cell Lung Cancer in Phase 2 Trials and in Real-world Data.

Importance: Quantitative assessment of bias from unmeasured confounding and missing data can help evaluate uncertainty in findings from indirect comparisons using real-world data (RWD). Objective: To compare the effectiveness of alectinib vs ceritinib in terms of overall survival (OS) in patients with ALK-positive, crizotinib-refractory, non-small cell lung cancer (NSCLC) and to assess the sensitivity of these findings to unmeasured confounding and missing data assumptions. Design, Setting, and Participants: This comparative effectiveness research study compared patients from 2 phase 2 alectinib trials and real-world patients. Patients were monitored from June 2013 to March 2020. Comparisons of interest were between alectinib trial data vs ceritinib RWD and alectinib RWD vs ceritinib RWD. RWD treatment groups were selected from nationally representative cancer data from US cancer clinics, the majority from community centers. Participants were ALK-positive patients aged 18 years or older with advanced NSCLC, prior exposure to crizotinib, and Eastern Cooperative Oncology Group Performance Status (PS) of 0 to 2. Data analysis was performed from October 2020 to March 2021. Exposures: Initiation of alectinib or ceritinib therapy. Main Outcomes and Measures: The main outcome was OS. Results: In total, there were 355 patients: 183 (85 men [46.4%]) in the alectinib trial, 91 (43 men [47.3%]) in the ceritinib RWD group, and 81 (38 men [46.9%]) in the alectinib RWD group. Patients in the alectinib trial were younger (mean [SD] age, 52.53 [11.18] vs 57.97 [11.71] years), more heavily pretreated (mean [SD] number of prior therapy lines, 1.95 [0.72] vs 1.47 [0.81]), and had more favorable baseline ECOG PS (ECOG PS of 0 or 1, 165 patients [90.2%] vs 37 patients [77.1%]) than those in the ceritinib RWD group. The alectinib RWD group (mean [SD] age, 58.69 [11.26] years) had more patients with favorable ECOG PS (ECOG PS of 0 or 1, 49 patients [92.4%] vs 37 patients [77.1%]) and more White patients (56 patients [72.7%] vs 53 patients [62.4%]) compared with the ceritinib group. Compared with ceritinib RWD, alectinib-exposed patients had significantly longer OS in alectinib trials (adjusted hazard ratio [HR], 0.59; 95% CI, 0.44-0.75; P < .001) and alectinib RWD (HR, 0.46; 95% CI, 0.29-0.63; P < .001) after adjustment for baseline confounders. For the worst-case HR estimate of 0.59, residual confounding by a hypothetical confounder associated with mortality and treatment by a risk ratio greater than 2.24 was required to reverse the findings. Conclusions were robust to plausible deviations from random missingness for missing ECOG PS and underrecorded comorbidities and central nervous system metastases in RWD. Conclusions and Relevance: Alectinib exposure was associated with longer OS compared with ceritinib in patients with ALK-positive NSCLC, and only substantial levels of bias examined reversed the findings. These findings suggest that quantitative bias analysis can be a useful tool to address uncertainty of findings for decision-makers considering RWD.

Cost-Effectiveness of Dipeptidylpeptidase-4 Inhibitors Added to Metformin in Patients With Type 2 Diabetes in China.

Purpose: Dipeptidylpeptidase-4 (DPP-4) inhibitors, including linagliptin, alogliptin, saxagliptin, sitagliptin, and vildagliptin, are used for the treatment of type 2 diabetes mellitus (T2DM) patients in China. This study assessed the economic outcomes of different DPP-4 inhibitors in patients with T2DM inadequately controlled with metformin in the Chinese context. Materials and Methods: In this study, the validated Chinese Outcomes Model for T2DM (COMT) was conducted to project economic outcomes from the perspective of Chinese healthcare service providers. Efficacy and safety, medical expenditure, and utility data were derived from the literature, which were assigned to model variables. The primary outputs of the model included the lifetime costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). One-way and probability sensitivity analysis was conducted to assess the potential uncertainties of parameters. Results: Of the five competing strategies, alogliptin 25 mg strategy yielded the most significant health outcome, which associated with improvements in discounted QALY of 0.007, 0.014, 0.011, and 0.022 versus linagliptin 5 mg, saxagliptin 5 mg, sitagliptin 100 mg and vildagliptin50 mg, respectively. The sitagliptin 100 mg strategy was the cheapest option. The ICER of alogliptin 25 mg against sitagliptin 100 mg strategy was $6,952 per additional QALY gained, and the rest of the strategies were dominated or extended dominated. The most influential parameters were the cost of DPP-4 inhibitors and their treatment efficacy. Conclusions: These results suggested that alogliptin was a preferred treatment option compared with other DPP-4 inhibitors for Chinese patients whose T2DM are inadequately controlled on metformin monotherapy.

Cost-effectiveness analysis of tofacitinib compared with adalimumab and etanercept in the treatment of severe active rheumatoid arthritis; Iranian experience.

BACKGROUND AND OBJECTIVE: This study aimed to evaluate the cost-utility of Tofacitinib (TFC) in patients with severe rheumatoid arthritis (RA) who had not responded well to methotrexate from the Iranian payer's perspective. METHODS: An individual microsimulation Markov model was developed to compare TFC with etanercept (ETN) and Adalimumab (ADA) over a life-time horizon. Treatment efficacy was estimated based on the American College of Rheumatology (ACR) response improvement criteria in 6 months. Changes in the Health Assessment Questionnaire (HAQ) scores were mapped onto utility values to calculate outcomes in terms of QALYs. Direct medical costs were taken from national databases. Uncertainty in model parameters was evaluated by sensitivity analyses. RESULTS: This study demonstrated that TFC was cost-effective in both scenarios. Although TFC was associated with lower QALYs than ETN (6.664 versus 6.876), it was also associated with lower costs over a life-time horizon ($42,565.04 versus $58,696.29). Additionally, TFC was found to be the dominant strategy with a lower cost ($50,299.91 versus $51,550.29) and higher QALYs gained (6.900 versus 6.687) compared to ADA. CONCLUSION: TFC was found to be cost-effective in patients with severe RA who do not respond well to methotrexate compared to ADA, ETN in Iran.

Tofacitinib for the Treatment of Ulcerative Colitis: Analysis of Infection Rates from the Ulcerative Colitis Clinical Programme.

BACKGROUND AND AIMS: Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis. We report integrated analyses of infections in the Phase [P]2 and P3 OCTAVE programmes. METHODS: Three cohorts were analysed: Induction [P2/3 induction studies]; Maintenance [P3 maintenance study]; and Overall [all tofacitinib-treated patients in induction, maintenance, or ongoing, open-label, long-term extension studies; as of May 2019]. Proportions and incidence rates [IRs; unique patients with events/100 patient-years] of serious infections [SIs], herpes zoster [HZ] [non-serious and serious], and opportunistic infections [OIs] are reported [censored at time of event]. RESULTS: In the Induction Cohort [N = 1220], no patients receiving placebo and eight [0.9%] receiving tofacitinib 10 mg twice daily [BID] developed SIs. Maintenance Cohort [N = 592] SI IRs (95% confidence interval [CI]) were 1.94 [0.23-7.00] for placebo and 1.35 [0.16-4.87] and 0.64 [0.02-3.54] for tofacitinib 5 and 10 mg BID, respectively; HZ IRs were 0.97 [0.02-5.42], 2.05 [0.42-6.00], and 6.64 [3.19-12.22], respectively. In the Overall Cohort [N = 1157; 82.9% predominantly received tofacitinib 10 mg BID], SI, HZ, and non-HZ OI IRs were 1.70 [1.24-2.27], 3.48 [2.79-4.30], and 0.15 [0.04-0.38], respectively. No SIs resulted in death. CONCLUSIONS: During induction, SIs were more frequent with tofacitinib versus placebo. SIs were generally infrequent in the Maintenance and Overall Cohorts, with rates comparable between treatment groups. Maintenance Cohort HZ IR was numerically higher with tofacitinib 10 mg BID versus 5 mg BID. Overall Cohort HZ IRs remained stable over time. Non-HZ OIs and viral infections were rare.

Assessment of Target Engagement in a First-in-Human Trial with Sinbaglustat, an Iminosugar to Treat Lysosomal Storage Disorders.

In this first-in-human study, the tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple oral doses of sinbaglustat, a dual inhibitor of glucosylceramide synthase (GCS) and non-lysosomal glucosyl ceramidase (GBA2), were investigated in healthy subjects. The single-ascending dose (SAD) and multiple-ascending dose (MAD) studies were randomized, double-blind, and placebo-controlled. Single doses from 10 to 2,000 mg in men and multiple doses from 30 to 1,000 mg twice daily for 7 days in male and female subjects were investigated. Tolerability, PK, and PD data were collected up to 3 days after (last) treatment administration and analyzed descriptively. Sinbaglustat was well-tolerated in the SAD and MAD studies, however, at the highest dose of the MAD, three of the four female subjects presented a similar pattern of general symptoms. In all cohorts, sinbaglustat was rapidly absorbed. Thereafter, plasma concentrations decreased biphasically. In the MAD study, steady-state conditions were reached on Day 2 without accumulation. During sinbaglustat treatment, plasma concentrations of glucosylceramide (GlcCer), lactosylceramide, and globotriaosylceramide decreased in a dose-dependent manner, reflecting GCS inhibition. The more complex the glycosphingolipid, the more time was required to elicit PD changes. After treatment stop, GlcCer levels returned to baseline and increased above baseline at lowest doses, probably due to the higher potency of sinbaglustat on GBA2 compared to GCS. Overall, sinbaglustat was welltolerated up to the highest tested doses. The PK profile is compatible with b.i.d. dosing. Sinbaglustat demonstrated target engagement in the periphery for GCS and GBA2.

Continuation of Anti-TNF in Patients With Ulcerative Colitis in Remission Is Not Cost-effective Compared With Treatment Withdrawal: A Markov Model.

BACKGROUND AND AIMS: Anti-tumour necrosis factor alpha [anti-TNF] treatment accounts for 31% of health care expenditures associated with ulcerative colitis [UC]. Withdrawal of anti-TNF in patients with UC in remission may decrease side effects and infections, while promoting cost containment. Approximately 36% of patients relapse within 12-24 months of anti-TNF withdrawal, but reintroduction of treatment is successful in 80% of patients. We aimed to evaluate the cost-effectiveness of continuation versus withdrawal of anti-TNF in patients with UC in remission. METHODS: We developed a Markov model comparing cost-effectiveness of anti-TNF continuation versus withdrawal, from a health care provider perspective. Transition probabilities were calculated from literature, or estimated by an expert panel of 11 gastroenterologists. Deterministic and probabilistic sensitivity analyses were performed to account for assumptions and uncertainty. The cost-effectiveness threshold was set at an incremental cost-effectiveness ratio of €80,000 per quality-adjusted life-year [QALY]. RESULTS: At 5 years, anti-TNF withdrawal was less costly [-€10,781 per patient], but also slightly less effective [-0.04 QALY per patient] than continued treatment. Continuation of anti-TNF compared with withdrawal costs €300,390/QALY, exceeding the cost-effectiveness threshold. Continued therapy would become cost-effective if the relapse rate following anti-TNF withdrawal was ≥43% higher, or if adalimumab or infliximab [biosimilar] prices fell below €87/40 mg and €66/100 mg, respectively. CONCLUSIONS: Continuation of anti-TNF in UC patients in remission is not cost-effective compared with withdrawal. A stop-and-reintroduction strategy is cost-saving but is slightly less effective than continued therapy. This strategy could be improved by identifying patients at increased risk of relapse.

Cost-effectiveness analysis of infliximab, adalimumab, golimumab, vedolizumab and tofacitinib for moderate to severe ulcerative colitis in Spain.

OBJECTIVE: Despite the biological drugs, the treatment of moderate to severe ulcerative colitis is still a challenge, particularly in resource-limited settings. The aim of this study was to assess the efficiency of biological drugs and tofacitinib for moderate to severe ulcerative colitis in the Spanish context. METHODS: A Markov model was built to simulate the progression of moderate to severe ulcerative colitis in a cohort of patients. The model used a time horizon of 10 years. The perspective chosen was the National Health Service, with a discount rate of 3%, and a threshold of €30,000/quality adjusted life-year (QALY). It carried out a one-way sensitivity analysis and probabilistic sensitivity analysis. RESULTS: The comparison of infliximab with adalimumab and golimumab estimated an incremental cost-effectiveness ratio (ICER) of €43,928.07/QALY and €31,340.69/QALY, with a difference of - 0.43 and - 0.82 QALY, respectively. Vedolizumab vs infliximab achieved an ICER of €122,890.19/QALY with a gain of 0.46 QALY. The comparison of infliximab with tofacitinib yielded an estimated ICER of €270,503.19/QALY, with a slight gain in QALY (0.16). The one-way sensitivity analysis showed a robust study. CONCLUSION: For a threshold of €30,000/QALY, adalimumab was the most cost-effective treatment versus infliximab for moderate to severe ulcerative colitis in Spain.

Time to Next Treatment, Health Care Resource Utilization, and Costs Associated with Ibrutinib Use Among U.S. Veterans with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Real-World Retrospective Analysis.

BACKGROUND: Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is the most common adult leukemia, accounting for ≈ 37% of all leukemias in the United States. Limited real-word evidence is available on the outcomes of ibrutinib use among previously untreated patients in the U.S. Veterans Health Administration (VHA) population diagnosed with CLL/SLL. OBJECTIVES: To (a) evaluate time to next treatment (TTNT) among U.S. veterans with CLL/SLL who initiated ibrutinib versus chemoimmunotherapy (CIT) in first line (1L) and 1L ibrutinib versus ibrutinib in later lines (2L+) and (b) compare health care resource utilization (HRU) and costs between the 1L ibrutinib and CIT cohorts. METHODS: Adults with CLL/SLL and claims for 1L single-agent ibrutinib or CIT (index date = first prescription claim date) were included from Veterans Health Administration Data (April 1, 2013-March 31, 2018). A subset of the CIT 1L cohort with evidence of ibrutinib in 2L/3L was defined as the ibrutinib 2L+ cohort. Kaplan-Meier curves and Cox proportional hazard models were used to evaluate TTNT, and generalized linear models were used to determine all-cause per patient per month (PPPM) HRU and costs during 1L among propensity score-matched (PSM) cohorts. RESULTS: After PSM, 614 patients were included in each of the 1L ibrutinib and 1L CIT cohorts, and 149 were included in each of the 1L ibrutinib and 2L+ ibrutinib cohorts. The 1L ibrutinib cohort had significantly longer TTNT compared with each of the 1L CIT and 2L+ ibrutinib cohorts (P <0.0001 and P =0.0001, respectively) and was less likely to have a next line of treatment than the CIT 1L cohort (HR = 0.52; 95% CI = 0.42-0.65; P < 0.0001) and the 2L+ ibrutinib cohort (HR = 0.39; 95% CI = 0.22-0.69; P = 0.0012). The 1L ibrutinib cohort had significantly fewer inpatient visits (rate ratio [RR] = 0.38; 95% CI = 0.28-0.52; P ≤ 0.05) and outpatient visits PPPM (RR =0.72; 95% CI = 0.68-0.77; P ≤ 0.5) compared with the CIT 1L cohort. Additionally, the 1L ibrutinib cohort had $7,308 significantly lower monthly medical costs (95% CI = -$9,892 to -$4,895; P ≤ 0.05) versus the 1L CIT cohort, resulting in comparable monthly total health care cost (medical and pharmacy) between real-world 1L patients treated by ibrutinib and CIT (-$2,160; 95% CI = -$4,840-$347; P > 0.05). CONCLUSIONS: These findings demonstrate that among U.S. veterans with CLL/SLL, 1L ibrutinib use was associated with significantly longer TTNT versus that of 1L CIT. Similarly, early treatment with ibrutinib was associated with longer TTNT as compared to ibrutinib use in later lines of therapy. Moreover, 1L ibrutinib was associated with lower HRU and medical costs compared with 1L CIT, completely offsetting the higher pharmacy costs related to 1L ibrutinib treatment. DISCLOSURES: This research was sponsored by Janssen Scientific Affairs. The analyses were performed by STATinMED Research. Huang is an employee of Janssen Scientific Affairs and may own company stock. Sundaram was an employee of Janssen Scientific Affairs at the time this study was conducted. Borra and Janjan are employees of STATinMED Research, a paid consultant to the study sponsor. Wang, Li, and Shrestha were employees of STATinMED Research at the time this study was conducted.

Movement of Poly-ADP Ribose (PARP) Inhibition into Frontline Treatment of Ovarian Cancer.

The use of poly (ADP-ribose) polymerase (PARP) inhibitors in the front-line management of advanced ovarian cancer has recently emerged as an exciting strategy with the potential to improve outcomes for patients with advanced ovarian cancer. In this article, we review the results of four recently published Phase III randomised controlled trials evaluating the use of PARP inhibitors in the primary treatment of ovarian cancer (SOLO1, PRIMA, PAOLA-1, and VELIA). Collectively, the studies suggest that PARP maintenance in the upfront setting is most beneficial among patients with BRCA-associated ovarian cancers (hazard ratios range from 0.31 to 0.44), followed by patients with tumours that harbour homologous recombination deficiencies (hazard ratios range from 0.33 to 0.57). All three studies that included an all-comer population were able to demonstrate benefit of PARP inhibitors, regardless of biomarker status. The FDA has approved olaparib for front-line maintenance therapy among patients with BRCA-associated ovarian cancers, and niraparib for all patients, regardless of biomarker status. In determining which patients should be offered front-line maintenance PARP inhibitors, and which agent to use, there are multiple factors to consider, including FDA indication, dosing preference, toxicity, risks versus benefits for each patient population, and cost. There are ongoing studies further exploring the front-line use of PARP inhibitors, including the potential downstream effects of PARP-inhibitor resistance in the recurrent setting, combining PARP-inhibitors with other anti-angiogenic drugs, immunotherapeutic agents, and inhibitors of pathways implicated in PARP inhibitor resistance.

Niraparib maintenance in frontline management of ovarian cancer: a cost effectiveness analysis.

OBJECTIVES: Niraparib maintenance after frontline chemotherapy for advanced ovarian cancer extends progression free survival. The objective of this study was to determine the cost effectiveness of niraparib maintenance therapy in patients with newly diagnosed ovarian cancer. METHODS: Decision analysis models compared the cost of observation versus niraparib maintenance following chemotherapy for five groups: all newly diagnosed ovarian cancer patients (overall), those with homologous recombination deficiency, those harboring BRCA mutations (BRCA), homologous recombination deficiency patients without BRCA mutations (homologous recombination deficiency non-BRCA), and non-homologous recombination deficiency patients. Drug costs were estimated using average wholesale prices. Progression free survival was estimated from published data and used to estimate projected overall survival. Incremental cost effectiveness ratios per quality adjusted life year were calculated. Sensitivity analyses varying the cost of niraparib were performed. The willingness-to-pay threshold was set at US$100 000 per quality adjusted life year saved. RESULTS: For the overall group, the cost of observation was US$5.8 billion versus $20.5 billion for niraparib maintenance, with an incremental cost effectiveness ratio of $72 829. For the homologous recombination deficiency group, the observation cost was $3.0 billion versus $14.8 billion for niraparib maintenance (incremental cost effectiveness ratio $56 329). Incremental cost effectiveness ratios for the BRCA, homologous recombination deficiency non-BRCA, and non-homologous recombination deficiency groups were $58 348, $50 914, and $88 741, respectively. For the overall and homologous recombination deficiency groups, niraparib remained cost effective if projected overall survival was 2.2 and 1.5 times progression free survival, respectively. CONCLUSIONS: For patients with newly diagnosed ovarian cancer, maintenance therapy with niraparib was cost effective. Cost effectiveness was improved when analyzing those patients with homologous recombination deficiency and BRCA mutations. Efforts should continue to optimize poly-ADP-ribose polymerase utilization strategies.

Real world experience of poly (ADP-ribose) polymerase inhibitor use in a community oncology practice.

OBJECTIVE: This study aims to describe the real-world experience, including the clinical and financial burden, associated with PARP inhibitors in a large community oncology practice. METHODS: Retrospective chart review identified patients prescribed olaparib, niraparib or rucaparib for maintenance therapy or treatment of recurrent ovarian, primary peritoneal or fallopian tube cancer across twelve gynecologic oncologists between December 2016 and November 2018. Demographic, financial and clinical data were extracted. One PARP cycle was defined as a single 28-day period. For patients treated with more than one PARPi, each course was described separately. RESULTS: A total of 47 patients and 506 PARP cycles were identified (122 olaparib, 24%; 89 rucaparib, 18%; 294 niraparib, 58%). Incidence of grade ≥ 3 adverse events were similar to previously reported. Toxicity resulted in dose interruption, reduction and discontinuation in 69%, 63% and 29% respectively. Dose interruptions were most frequent for niraparib but resulted in fewer discontinuations (p-value 0.01). Mean duration of use was 7.46 cycles (olaparib 10.52, rucaparib 4.68, niraparib 7.34). Average cost of PARPi therapy was $8018 per cycle. A total of 711 phone calls were documented (call rate 1.4 calls/cycle) with the highest call volume required for care coordination, lab results and toxicity management. CONCLUSIONS: Although the toxicity profile was similar to randomized clinical trials, this real-world experience demonstrated more dose modifications and discontinuations for toxicity management than previously reported. Furthermore, the clinical and financial burden of PARP inhibitors may be significant and future studies should assess the impact on patient outcomes.

Blinded SAPS-PD Assessment After 10 Weeks of Pimavanserin Treatment for Parkinson's Disease Psychosis.

BACKGROUND: Parkinson's disease psychosis (PDP) is a common nonmotor symptom that affects up to 60% of patients. Pimavanserin, a selective 5-HT2A inverse agonist/antagonist, is approved for treating hallucinations and delusions associated with PDP. OBJECTIVE: Evaluate the efficacy and tolerability of pimavanserin in an open-label extension (OLE) study. METHODS: Patients completing a pivotal 6-week placebo-controlled trial (Core Study) could enroll in the OLE. All patients pimavanserin 34 mg once daily, blinded to previous treatment allocation. Prespecified blinded assessments at Week 4 were the Scale for the Assessment of Positive Symptoms (SAPS) PD version and SAPS H + D scales, Caregiver Burden Scale (CBS), and Clinical Global Impression (CGI) Improvement and Severity scales. RESULTS: Of 171 who entered the OLE, 148 (87%) completed Week 4. Among patients who received placebo in the Core Study, mean (SD) change from OLE baseline to OLE Week 4 for the SAPS-PD was - 3.4 (6.3); p < 0.0001. Mean change from Core Study baseline to OLE Week 4 for SAPS-PD was similar among prior pimavanserin- and placebo-treated patients (-6.9 vs. -6.3). Improvement was similar with CGI-I, CGI-S, CBS, and SAPS-H + D in patients previously treated with placebo. Adverse events occurred in 92 (53.8%) patients during the 4-week OLE. CONCLUSION: Improvements at OLE Week 4 from pretreatment baseline were similar with placebo and pimavanserin in the Core Study. The beneficial effects observed with pimavanserin in the 6-week Core Study were maintained for 4 weeks in the blinded OLE, supporting the durability of response with pimavanserin 34 mg for PDP over 10 weeks.

Alvimopan Is Associated With a Reduction in Length of Stay and Hospital Costs for Patients Undergoing Radical Cystectomy.

OBJECTIVE: To evaluate the impact of alvimopan in patient undergoing radical cystectomy (RC) for bladder cancer. We hypothesize that alvimopan can decrease cost for RC by reducing length of stay (LOS). METHODS: We identified patients who underwent elective RC for bladder cancer from 2009 to 2015 in the Premier Healthcare Database, a nationwide, all-payer hospital-based database, and compared patients who received and did not receive alvimopan in the perioperative period. Hospitals that had no record of administering alvimopan for patients undergoing RC were excluded. The primary outcomes were LOS and the direct hospital costs. The secondary outcomes were 90-day readmission for ileus and major complications. RESULTS: After applying the inclusion criteria, the study cohort consisted of 1087 patients with 511 patients receiving perioperative alvimopan. Alvimopan was associated with a reduction in hospital costs by -$2709 (95% confidence interval: -$4507 to -$912, P = .003), decreased median LOS (7 vs 8 days, P < .001), and lower likelihood of readmission for ileus (adjusted odds ratio: 0.63, P = .041). While alvimopan use led to higher pharmacy costs, this was outweighed by lower room and board costs due to the reduced LOS. There was no significant difference between 2 groups regarding major complications. These results were robust across multiple adjusted regression models. CONCLUSION: Our data show that alvimopan is associated with a substantial cost-saving in patients undergoing RC, and suggest that routine use of alvimopan may be a potential cost-effective strategy to reduce the overall financial burden of bladder cancer.

How the Beneficial Effects of Alvimopan Differ With Surgical Approach for Radical Cystectomy.

OBJECTIVE: To assess whether the beneficial perioperative effects of alvimopan differ with surgical approach for patients who undergo open radical cystectomy (ORC) vs robot-assisted radical cystectomy (RARC). METHODS: This retrospective study reviewed all patients who underwent cystectomy with urinary diversion at our institution between January 1, 2007, and January 1, 2018. Data were collected on demographic characteristics, comorbidities, surgical approach, alvimopan therapy, hospital length of stay (LOS), days until return of bowel function (ROBF), and complications. Outcomes and interactions were evaluated through regression analysis. RESULTS: Among 573 patients, 236 (41.2%) underwent RARC, 337 (58.8%) underwent ORC, and 205 (35.8%) received alvimopan. Comparison of 4 cohorts (ORC with alvimopan, ORC without alvimopan, RARC with alvimopan, and RARC without alvimopan) showed that patients who underwent ORC without alvimopan had the highest rate of postoperative ileus (25.6%, P = .02), longest median hospital LOS (7 days, P < .001), and longest time until ROBF (4 days, P < .001). On multivariable analysis, the interaction between surgical approach and alvimopan use was significant for the outcome of ROBF (estimate, 1.109; 95% confidence interval, 0.418-1.800; P = .002). In the RARC cohort, multivariable analysis showed no benefit of alvimopan with respect to ileus (P = .27), LOS (P = .09), or ROBF (P = .36). Regarding joint effects of robotic approach and alvimopan, RARC had no effect on gastrointestinal tract outcomes. CONCLUSION: We observed a diminished beneficial effect of alvimopan among patients undergoing RARC and a statistically significant benefit of alvimopan among patients undergoing ORC. The implications of these findings may permit more selective medication use for patients who would benefit the most from this drug.

Cost-effectiveness of niraparib, rucaparib, and olaparib for treatment of platinum-resistant, recurrent ovarian carcinoma.

BACKGROUND: Olaparib was approved on December 19, 2014 by the US FDA as 4th-line therapy (and beyond) for patients with germline BRCA1/2 mutations; rucaparib was approved on December 19, 2016 as 3rd-line therapy (and beyond) for germline or somatic BRCA1/2-mutated recurrent disease. On October 23, 2019, niraparib was approved for treatment of women with damaging mutations in BRCA1/2 or other homologous recombination repair genes who had been treated with three or more prior regimens. We compared the cost-effectiveness of PARPi(s) with intravenous regimens for platinum-resistant disease. METHODS: Median progression-free survival (PFS) and toxicity data from regulatory trials were incorporated in a model which transitioned patients through response, hematologic complications, non-hematologic complications, progression, and death. Using TreeAge Pro 2017, each PARPi(s) was compared separately to non­platinum-based and bevacizumab-containing regimens. Costs of IV drugs, managing toxicities, infusions, and supportive care were estimated using 2017 Medicare data. Incremental cost-effectiveness ratios (ICERs) were calculated and PFS was reported in quality adjusted life months for platinum-resistant populations. RESULTS: Non­platinum-based intravenous chemotherapy was most cost effective ($6,412/PFS-month) compared with bevacizumab-containing regimens ($12,187/PFS-month), niraparib ($18,970/PFS-month), olaparib ($16,327/PFS-month), and rucaparib ($16,637/PFS-month). ICERs for PARPi(s) were 3-3.5× times greater than intravenous non­platinum-based regimens. CONCLUSION: High costs of orally administered PARPi(s) were not mitigated or balanced by costs of infusion and managing toxicities of intravenous regimens typically associated with lower response and shorter median PFS. Balancing modest clinical benefit with costs of novel therapies remains problematic and could widen disparities among those with limited access to care.

Cost-effectiveness of alectinib compared to crizotinib for the treatment of first-line ALK+ advanced non-small-cell lung cancer in France.

The aim of the study is to evaluate the cost-effectiveness of alectinib for first-line treatment of ALK+ advanced non-small-cell lung cancer compared to crizotinib in the French setting. This study used a partitioned survival model, with three discrete health states (progression-free survival, post-progression survival and death). Survival probabilities were derived from a randomised Phase III clinical trial comparing alectinib to crizotinib (ALEX). Beyond the length of the trial (18 months), the efficacy of both treatments was considered equivalent. Occurrence of adverse events or brain metastases were considered as inter-current events. Utilities (and disutilities for intercurrent adverse events) derived from the EQ-5D were applied. Costs were attributed using standard French national public health tariffs. Projected mean overall survival was 4.62 years for alectinib and 4.18 years for crizotinib. Projected mean progression-free survival was 30.30 months for alectinib and 16.13 months for crizotinib. The total number of quality-adjusted life years projected was 3.40 for alectinib and 2.84 for crizotinib. The projected total cost of treatment over the lifetime of the model was € 246,022 for alectinib and € 195,486 for crizotinib. This extra cost was principally attributable to treatment acquisition costs and management before progression. Alectinib was associated with lower costs related to brain metastases and to management post-progression. The incremental cost per life year gained was 115,334 €/year and the incremental cost-effectiveness ratio was 90,232 €/QALY. First-line treatment of ALK+ NSCLC with alectinib provides superior clinical outcomes to crizotinib and is cost-effective in the French context.