Cost-Effectiveness Analysis of Erenumab Versus OnabotulinumtoxinA for Patients with Chronic Migraine Attacks in Greece

DOI: https://doi.org/10.1007/s40261- 019- 00827- z

Abstract-Summary Existing preventive treatments involve the selective use of onabotulinumtoxinA, which aims at migraine morbidity reduction for patients who have failed initial preventive treatment with oral agents.

Erenumab is a new preventive treatment for migraines. To evaluate the differences in costs and outcomes of the preventive treatment with erenumab versus onabotulinumtoxinA in patients with chronic migraines (CM) in Greece to assess the economic value of this treatment.

We conducted a cost-effectiveness analysis from both the payer and the societal

perspective using a decision-tree analytic model.

Indirect costs for the societal perspective analyses included wages lost on

workdays.

Our results indicate that treatment of CM with erenumab compared to onabotu- linumtoxinA resulted in incremental cost-effectiveness ratios (ICERs) of €218,870 and €231,554 per QALY gained and €620 and €656 per migraine avoided, from the societal and the payer’s perspective, respectively.

Using a common cost-effectiveness threshold equal to three times the local gross domestic product (GDP) per capita (€49,000), for the erenumab ICERs to fall below this threshold, the erenumab price would have to be no more than €192 (societal perspective) or €173 (payer perspective).

The prophylactic treatment of CM with erenumab in Greece might be cost effec- tive compared to the existing alternative of onabotulinumtoxinA from both the payer and the societal perspective, but only at a highly discounted price.

Erenumab could be considered a therapeutic option for patients who fail treat-

ment with onabotulinumtoxinA.

Extended: One-way and probabilistic sensitivity analyses were conducted to evaluate the robustness of the findings and to account for the effect of the uncer- tainty of key model inputs on the ICER.

Introduction Preventive therapies are deemed appropriate for patients who suffer from higher frequencies of migraines, namely those classified as episodic migraineurs (EM), with 4–14 migraines per month, and chronic migraineurs (CM), with 15 or more migraines per month [182].

Topiramate, an antiepileptic drug that was found to be highly cost effective in preventing migraines by modulating the trigeminovascular signaling, is currently used as a first-line preventive therapy for CM in Greece [466–469].

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Clinical trials indicated that, compared to the placebo, erenumab led to a signifi- cant reduction in the monthly frequency of migraines and to sustained improve- ments in psychosocial and disability-related outcomes in patients with CM [470, 471].

The objective of this study was to examine the cost effectiveness of erenumab 140  mg compared to the existing preventive treatment with ONBTA for patients with CM from the payer and the societal perspective in Greece.

Methods Similar to previous studies, we further adjusted our model to account for costs of lost productivity for migraine attacks during workdays [350].

Since triptans are more effective in mitigating the symptoms of a migraine crisis compared to no acute care medication or to usual care, we assigned different out- comes for working hours lost, depending on the choice of acute treatment therapy.

The difference in migraine reduction between ONBTA and erenumab was obtained through the following formula:where ΔTE[O|P] indicates the difference in treatment effects in the placebo-controlled trials for ONBTA, obtained through weighted pooling of the two studies’ outcomes, ΔTE[E|P] the difference in treatment effects in the placebo-controlled trials for erenumab, and ΔTE[E|O] the analogous difference in treatment effects between the two drugs of interest.

Based on Greek experts’ feedback, patients with CM use acute treatment medi- cations to mitigate the symptoms of a migraine crisis at an approximate rate of 80% during ongoing attacks.

Results The annual cost difference between erenumab and ONBTA was €216 higher from the payer’s perspective (€3936), attributed mainly to the exclusion of indirect costs and out-of-pocket payments from payer costs.

The greater effectiveness of erenumab in migraine reduction had a stronger impact on the ICER from the societal perspective compared to the payer perspective.

Even when we adjusted our sensitivity analyses to account only for the ONBTA lower adherence identified in Greek patients’ study, the ICER remained above €100,000, driven by the higher costs associated with the use of healthcare services, acute medications, and productivity costs (societal perspective) [472].

We also conducted a price and co-pay threshold analysis from the payer’s per- spective to explore the potential impact of a lower negotiated price for erenumab, coupled with shifting a higher share of the cost of purchasing erenumab from the national health-insurance payer to the patient by establishing various patient co- pay levels.

Discussion This study offers critical insight into the decisions that have to be made in the immi- nent future regarding treatment guidelines for CM, price negotiations for erenumab, and cost-sharing policies towards value-based payment [473].

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Economics

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In the case of Greece, economic evaluations have not received the same attention compared to other countries; possible reasons for that could be related to a less developed Health Technology Assessment (HTA) and reimbursement environment in Greece, coupled with the absence of an officially established willingness-to-pay threshold to define which treatments are likely to be considered cost effective.

Our base-case finding of an incremental difference of 0.017 QALYs gained for the erenumab treatment aligns with previous research using different cost- effectiveness methodologies, which found incremental differences of 0.03 and 0.18 QALYs gained over a 2- or 10-year time horizon, respectively, indicating the con- sistency of our model [343, 350].

Conclusion The additional benefit of erenumab treatment in terms of migraines averted and QALYs gained for patients with chronic migraines in Greece will exceed commonly accepted willingness-to-pay thresholds based on this analysis.

In the absence of an officially established threshold of willingness-to-pay for new healthcare technologies in Greece, coupled with the large proportion of patients who cannot tolerate topiramate (due to its adverse effects), erenumab could be included in the national drug formulary and in the local clinical guidelines for treat- ment of CM as a third-line treatment option, when initial treatment with antiepilep- tic agents fails, and subsequent treatment with ONBTA also fails.

Acknowledgement A machine generated summary based on the work of Giannouchos, Theodoros V.; Mitsikostas, Dimos-Dimitrios; Ohsfeldt, Robert L.; Vozikis, Athanassios; Koufopoulou, Paraskevi. 2019 in Clinical Drug Investigation.

Costs of Acute Headache Medication Use and Productivity Losses Among Patients with Migraine: Insights from Three Randomized Controlled Trials