Cost-consequence analysis of ofatumumab for the treatment of relapsing-remitting multiple sclerosis in Canada.

Aim: The costs and consequences of initial and delayed ofatumumab treatment were evaluated in relapsing-remitting multiple sclerosis with active disease in Canada. Materials & methods: A Markov cohort model was used (10-year horizon, annual cycle length, 1.5% discounting). Scenario analyses examined ofatumumab as first-line treatment versus 3 and 5 years following switch from commonly used first-line therapies. Results: Ofatumumab resulted in improvements in clinical outcomes (relapses and disease progression) and productivity (employment and full-time work), and reduction of economic burden (administration, monitoring and non-drug costs) that were comparable to other high-efficacy therapies (ocrelizumab, cladribine and natalizumab). Switching to ofatumumab earlier in the disease course may improve these outcomes. Conclusion: Results highlight the value of a high-efficacy therapy such as ofatumumab as initial treatment (i.e., first-line) in newly diagnosed relapsing-remitting multiple sclerosis patients with active disease.

Comparing the long-term clinical and economic impact of ofatumumab versus dimethyl fumarate and glatiramer acetate in patients with relapsing multiple sclerosis: A cost-consequence analysis from a societal perspective in Germany.

Background: Evidence suggests that early highly efficacious therapy in relapsing multiple sclerosis is superior to escalation strategies. Objective: A cost-consequence analysis simulated different treatment scenarios with ofatumumab (OMB), dimethyl fumarate (DMF) and glatiramer acetate (GA): immediate OMB initiation as first treatment, early switch to OMB after 1 year on DMF/GA, late switch after 5 years or no switch. Methods: An EDSS-based Markov model with a 10-year time horizon was applied. Cycle transitions included EDSS progression, improvement or stabilization, treatment discontinuation, relapse or death. Input data were extracted from OMB trials, a network meta-analysis, published literature, and publicly available sources. Results: The late switch compared to the immediate OMB scenario resulted in a lower proportion of patients with EDSS 0-3 (Δ - 7.5% DMF; Δ - 10.3% GA), more relapses (Δ + 0.72 DMF; Δ + 1.23 GA) and lower employment rates (Δ - 4.0% DMF; Δ - 5.6% GA). The same applies to late versus early switches. No switch scenarios resulted in worse outcomes. Higher drug acquisition costs in the immediate OMB and early switch scenarios were almost compensated by lower costs for patient care and productivity loss. Conclusion: Immediate OMB treatment and an early switch improves clinical and productivity outcomes while remaining almost cost neutral compared to late or no switches.

Cost Effectiveness and Budget Impact of Siponimod Compared to Interferon Beta-1a in the Treatment of Adult Patients with Secondary Progressive Multiple Sclerosis with Active Disease in Switzerland.

OBJECTIVE: The study aim was to evaluate the cost effectiveness and budget impact of siponimod compared to interferon beta-1a for adult patients with secondary progressive multiple sclerosis (SPMS) with active disease, from a Swiss health insurance perspective. METHODS: We conducted an analysis using a Markov cohort model with a cycle length of 1 year, life-long time horizon, and discount rate of 3% for cost and health outcomes. We used a matching-adjusted indirect comparison to estimate clinical outcomes using data from the EXPAND randomised controlled trial of siponimod vs placebo and the Nordic SPMS randomised controlled trial of interferon beta-1a vs placebo as the basis for estimates of disability progression and relapse outcomes. We used 6-month confirmed disability progression results to estimate disability progression in the base-case analysis. We calculated quality-adjusted life-years (QALYs) based on an external study that administered the EQ-5D-3L questionnaire to European patients with multiple sclerosis. We included costs (Swiss Franc (CHF), year 2020) of drug acquisition/administration, adverse events and disease management. We also performed a budget impact analysis to estimate the cost over the first 3 years of introducing siponimod. RESULTS: For the base case, siponimod resulted in mean incremental costs of CHF 84,901 (siponimod: CHF 567,838, interferon beta-1a: CHF 482,937) and mean incremental QALYs of 1.591 (siponimod: 7.495, interferon beta-1a: 5.905), leading to an incremental cost-effectiveness ratio of CHF 53,364 per QALY gained. In the probabilistic sensitivity analysis, the probability of the cost effectiveness of siponimod assuming a willingness-to-pay threshold of CHF 100,000 per QALY gained was 90%. Siponimod was projected to result in drug administration costs for siponimod of CHF 23,817,856 in the first 3 years after introduction, accompanied by large cost offsets in drug acquisition of other multiple sclerosis drugs. Considering drug administration, monitoring and adverse event management costs, it was estimated to result in additional healthcare costs in Switzerland of CHF 2,177,021. CONCLUSIONS: In the base-case analysis, we found that siponimod may be cost effective for treating Swiss adult patients with SPMS with active disease. The results of the cost-effectiveness analyses are valid under the assumption that the efficacy of siponimod and the comparators on disability progression for the overall SPMS population would be the same in the active SPMS population. CLINICAL TRIAL IDENTIFIER: NCT01665144. This economic evaluation was based on the EXPAND trial.

Hindi version of short form of douleur neuropathique 4 (S-DN4) questionnaire for assessment of neuropathic pain component: a cross-cultural validation study.

BACKGROUND: Pain with neuropathic characteristics is generally more severe and associated with a lower quality of life compared to nociceptive pain (NcP). Short form of the Douleur Neuropathique en 4 Questions (S-DN4) is one of the most used and reliable screening questionnaires and is reported to have good diagnostic properties. This study was aimed to cross-culturally validate the Hindi version of the S-DN4 in patients with various chronic pain conditions. METHODS: The S-DN4 is already translated into the Hindi language by Mapi Research Trust. This study assessed the psychometric properties of the Hindi version of the S-DN4 including internal consistency and test-retest reliability after 3 days' post-baseline assessment. Diagnostic performance was also assessed. RESULTS: One hundred sixty patients with chronic pain, 80 each in the neuropathic pain (NeP) present and NeP absent groups, were recruited. Patients with NeP present reported significantly higher S-DN4 scores in comparison to patients in the NeP absent group (mean (SD), 4.7 (1.7) vs. 1.8 (1.6), P < 0.01). The S-DN4 was found to have an AUC of 0.88 with adequate internal consistency (Cronbach's α = 0.80) and a test-retest reliability (ICC = 0.92) with an optimal cut-off value of 3 (Youden's index = 0.66, sensitivity and specificity of 88.7% and 77.5%). The diagnostic concordance rate between clinician diagnosis and the S-DN4 questionnaire was 83.1% (kappa = 0.66). CONCLUSIONS: Overall, the Hindi version of the S-DN4 has good internal consistency and test-retest reliability along with good diagnostic accuracy.

Neuropathic Pain Assessment with the PainDETECT Questionnaire: Cross-Cultural Adaptation and Psychometric Evaluation to Hindi.

OBJECTIVE: The contribution of neuropathic pain (NeP) in chronic pain conditions is increasingly emphasized with the development of multiple questionnaire-based measurement scales. The painDETECT questionnaire (PDQ) is a frequently used self-reported outcome measure to assess NeP in patients with chronic pain conditions in research and regular clinical practice. The aim of the study was to translate and cross-culturally adapt the PDQ into Hindi (Hi-PDQ) for use in India and to investigate its psychometric properties. METHODS: PainDETECT questionnaire translation into the Hindi language was carried out according to standard guidelines. Patients suffering from chronic pain attending a pain clinic were recruited. Patients completed the Hi-PDQ at baseline and were retested was conducted after 3 days Exploratory factor analysis (EFA) was carried out to assess the factor structure of the Hi-PDQ. Measurement properties, including floor and ceiling effects, discriminative validity, and psychometric properties, were also assessed. RESULTS: A total of 160 patients with chronic pain were recruited, including 80 in each NeP and non-NeP group. The retest was completed in 82 patients. Mean Hi-PDQ scores were significantly higher in the NeP group compared with the non-NeP group (20.7 [SD 5.9] vs. 9.9 [SD 5.9]; P < 0.01). EFA revealed a 2-factor structure explaining 56.9% variance. The Hi-PDQ was found to have adequate internal consistency (Cronbach's alpha = 0.83), test-retest reliability (intraclass correlation coefficient = 0.94), and excellent discriminant validity (area under the curve = 0.88), with an optimal cutoff value of > 18 (sensitivity and specificity of 82.5% and 91.2%, respectively). CONCLUSION: The PDQ was successfully translated into the Hindi language. The Hi-PDQ showed good discriminative validity and psychometric properties. The Hi-PDQ is a reliable instrument to assess NeP in chronic pain conditions.