Relative frequency, characteristics, and disease burden of patients with migraine unsuitable for triptan treatment: A systematic literature review

Abstract

Objective: This review was conducted to systematically identify evidence characterizing patients with migraine who are unsuitable for triptans.

Background: Triptans are not suitable as first-line treatment for all patients with migraine due to contraindications, lack of efficacy, and/or poor tolerability. However, there is debate about the frequency and characteristics of these patients and the burden they experience.

Methods: MEDLINE, Embase, and conference abstracts (2011-2022) were reviewed for evidence on patients with migraine unsuitable for triptans for any reason. Data from publications describing the frequency and characteristics of this group, as well as the clinical, humanistic, or economic burden of disease in this population, were extracted.

Results: Of 1460 records screened, 29 publications met inclusion criteria. Persistence with triptans was low; 51%-66% of patients starting a new triptan did not refill it, and 43%-100% discontinued their initial triptan over 2 years. In one study, 14% of patients with migraine reported prior discontinuation/failure of ≥ 2 triptans due to inadequate efficacy or poor tolerability. Up to 15% of patients with migraine had triptan contraindications, and ≥ 20% of patients receiving triptans had contraindications. In four studies, 10%-44% of patients who tried triptans had insufficient response, although definitions varied. Patients who achieved a sufficient response typically did so with their first triptan; few became responders with additional triptans. Of patients who did not respond to one to two triptans and received another, 45% were dissatisfied with the final triptan. Approximately half of patients who tried two to three triptans had an insufficient response. Greater disability, impact of disease, and depression were reported in triptan discontinuers compared to those with sustained use. Worse quality of life scores and utility values were reported in triptan insufficient versus sufficient responders, as were greater migraine-related costs, work impairment, and health-care resource utilization.

Conclusion: The total population of patients unsuitable for triptans is uncertain, but the literature highlights a large group who cannot or do not persist with triptans, and current evidence suggests a high burden in this population and an unmet need for new therapeutic options. Further research is needed to determine the frequency of unsuitability for triptans more precisely and to assess the associated burden.

Keywords: insufficent response; migraine; treatment; triptan.

FIGURE 1

Preferred Reporting Items of Systematic Reviews and Meta‐Analyses diagram. CDSR, Cochrane Database of Systematic Reviews; CENTRAL, Cochrane Central Register of Controlled Trials; SLR, systematic literature review.

FIGURE 2

Treatment patterns at first refill among patients newly initiating triptans. Study population (n) = patients with a newly prescribed triptan. ^aDefinitions varied across the papers; Ng‐Mak et al., 2012: No further prescriptions for migraine ; Katić et al., 2011: No further prescriptions of specific or nonspecific migraine medications ; Chen et al., 2014: No further prescription of triptan or non‐triptan acute migraine medications. ^bClasses included (alone or in various combinations): Non‐narcotic analgesics, antipyretics, anti‐emetics, NSAIDs, ergot derivatives, and opioids (Ng‐Mak et al., 2012); opioids, salicylates, NSAIDs, barbiturates, and other non‐migraine drugs (Katić et al., 2011); salicylates, acetaminophen, opioids, NSAIDs, and ergotamines (Chen et al., 2014). ^cIn Fischer, 2016, rates were reported at first follow‐up, with a median time to first follow‐up of 24 weeks. Of 51 patients who discontinued all migraine medication or switched to a different class of therapy, 15 had ≥1 triptan(s) prior to the index triptan. The proportion of patients who refilled index triptan was calculated by subtracting the number of patients that switched to a different triptan (n = 19) from the number of patients with sustained use of any triptan (n = 75). NR, not reported; UK, United Kingdom; US, United States.

FIGURE 3

Number of unique triptans ever used in patients with insufficient and sufficient response to triptans. ^aIn these studies, triptan‐insufficient responders were those patients who reported achieving pain freedom within 2 h of taking their acute medication in ≤ 3 of their most recent 5 migraine attacks. ^bIn these studies, triptan sufficient responders were those patients who reported achieving pain freedom within 2 h of taking their acute medication in > 3 of their most recent 5 migraine attacks. Population all had triptan as their sole acute prescribed medication. EU, European Union; UK, United Kingdom; US, United States.

FIGURE 4

Clinical burden: Reasons for triptan discontinuation. ^aWells, 2014 included patients with episodic migraine (with or without aura), chronic migraine, or medication‐overuse headache. A total of 69 patients were asked to give their top reason for discontinuing triptans; 44% indicated lack of effect, 29% side effects, 8% safety, 6% had migraine disappear, < 5% gave other reasons. ^bFischer, 2016 included patients who had migraine with aura, migraine without aura, or chronic migraine, and a median of 6 monthly headache days. Patients were asked for reasons they discontinued triptans, and each patient could select more than one answer. Fifty‐one patients who discontinued a triptan provided 89 reasons for discontinuation; 18% of reasons were lack of effect, 13.5% side effects; other reasons (not shown here) included switch to another triptan (39.3%), other acute medication preferred (14.6%), contraindication (12.4%), [migraine] attack‐free (1.1%). ^cHolland, 2013 included patients with episodic migraine and a mean of 2.5 monthly headache days. A total of 247 patients were asked for reasons they discontinued triptans, and each patient could select more than one answer. Lack of efficacy was reflected in 34.7% of patients agreeing that the medication did not relieve headache sufficiently, 21.3% agreeing that the medication relieved headache pain but pain returned later, and 18.2% noted that the medication stopped working for them. Safety reasons were reflected in 17.8% of patients who noted that they had side effects.

FIGURE 5

Humanistic burden: Patients who discontinued versus continued triptans. ^aMIDAS Disability Score, ^bHIT Impact of Disease, and ^cBeck Depression Inventory. Wells, 2014 included patients with episodic migraine (with or without aura), chronic migraine, or medication‐overuse headache. Fischer, 2016 included patients who had migraine with aura, migraine without aura, or chronic migraine, and a median of 6 monthly headache days. HIT‐6, Headache Impact Test; MIDAS, Migraine Disability Assessment; QoL, quality of life; US, United States.

FIGURE 6

Humanistic burden: Patients with insufficient versus sufficient response to triptans. ^aMSQ Total Score, ^bEQ‐5D Utility Score. Hirata, 2021 included patients who had migraine with aura, migraine without aura, menstrual migraine, chronic migraine, medication‐overuse headache, and/or tension‐type headache. Patients had a mean of 4.2 monthly migraine days over the past 3 months, and a mean migraine severity of 5.7 on a scale of 1 (very mild) to 10 (very severe). Lombard, 2020 included patients who had migraine with aura, migraine without aura, menstrual migraine and/or chronic migraine, and a mean migraine severity of 5.6 to 5.9 on a scale of 1 (very mild) to 10 (very severe). LS, least squares; MSQ, Migraine‐Specific Quality of Life Questionnaire; QoL, quality of life; TIR, triptan‐insufficient responders; TR, triptans responders.

FIGURE 7

Economic burden in triptan insufficient versus sufficient responders. ^aPercent impairment while working, ^bWork missed due to migraine, and ^cTotal migraine‐related costs. Hirata, 2021 included patients who had migraine with aura, migraine without aura, menstrual migraine, chronic migraine, medication‐overuse headache, and/or tension‐type headache. Patients had a mean of 4.2 monthly migraine days over the past 3 months, and a mean migraine severity of 5.7 on a scale of 1 (very mild) to 10 (very severe). Lombard, 2020 included patients who had migraine with aura, migraine without aura, menstrual migraine and/or chronic migraine, and a mean migraine severity of 5.6 to 5.9 on a scale of 1 (very mild) to 10 (very severe). Marcus, 2020 included patients who had at least one migraine diagnosis. A diagnosis of chronic migraine was present in 5.2% of TRs and 9.2% of TIRs. CI, confidence interval; LS, least squares; NR, not reported; TIR, triptan‐insufficient responders; TR, triptans responders; USD, United States dollars; WPAI, Work Productivity and Impairment.