Triptan efficacy does not predict onabotulinumtoxinA efficacy but improves with onabotulinumtoxinA response in chronic migraine patients

DOI: https://doi.org/10.1038/s41598-020-68149-1

Abstract-Summary Botulinum toxin (onabotulinumtoxinA) is effective for treatment of CM, with ~ 50% of patients responding after 24 weeks.

We hypothesized that the response to triptans might predict response to onabotu- linumtoxinA.  Contrariwise, onabotulinumtoxinA treatment might affect triptan efficacy.

49 CM patients scheduled for their first onabotulinumtoxinA treatment were

included.

Before (T0) and three months after (T1) onabotulinumtoxinA treatment, patients

rated triptan efficacy and indicated number of headache days/month.

Triptan efficacy ratings at T0 did not predict onabotulinumtoxinA efficacy rat-

ings at T1 (p = 0.19) or reduction of headache days (p = 0.37).

Triptan efficacy significantly improved from T0 to T1 in onabotulinumtoxinA

responders (p < 0.001) but not in non-responders (p = 1.00).

Triptan efficacy did not predict response to onabotulinumtoxinA in CM. Triptan efficacy increased after successful onabotulinumtoxinA treatment.

Introduction One of the substances used for preventative treatment of chronic migraine is ona- botulinumtoxinA, which demonstrated a significant reduction of 8.4 headache days per month in the verum compared to the placebo group (6.6 days) after 24 weeks and two treatments.

Patients having more release of CGRP during their migraine attacks might react

better to onabotulinumtoxinA treatment.

It has been reported that chronic migraine patients have increased CGRP levels in peripheral blood, and more elevated CGRP levels are related to a better onabotu- linumtoxinA response [309, 310].

4.3 Results

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Triptans as well as onabotulinumtoxinA act by influencing the release of CGRP from trigeminal nerve fibres, we hypothesized that a good individual response to triptans in the acute migraine attack might predict a good response to onabotu- linumtoxinA in the preventative treatment of chronic migraine.

In order to test this hypothesis, we conducted a prospective study in chronic

migraine patients scheduled for their first onabotulinumtoxinA treatment.

Material and Methods Chronic migraine patients retrospectively indicated their headache frequency and triptan efficacy (see below) on the day of their first treatment with onabotulinum- toxinA (baseline, “T0”).

At follow-up (T1), patients answered the same questions, and additionally rated

the efficacy of onabotulinumtoxinA treatment.

At follow-up (T1) patients also rated the efficacy of onabotulinumtoxinA to

reduce their headaches (1 = very good, 2 = good, 3 = moderate, 4 = none).

Our primary hypothesis was that chronic migraine patients who report higher efficacy of triptans for acute migraine treatment would have a better response to onabotulinumtoxinA. Power analysis performed with G*Power [311] indicated that using a one-way analysis of variance (ANOVA) with onabotulinumtoxinA efficacy as dependent variable and triptan efficacy at T0 as factor with four levels, a sample size of n = 48 is sufficient to detect a large effect (f = 0.50) at p < 0.05 with a power of 0.80.

Results There was no significant relation between triptan efficacy ratings at T0 and onabotu- linumtoxinA efficacy ratings at T1 (Kruskal Wallis H = 4.83, p = 0.19, Spearman’s rho = 0.20, p = 0.16) or percent reduction of headache days from T0 to T1 (H = 3.18, p = 0.37, rho = −0.16, p = 0.29).

The triptan efficacy ratings significantly improved in headache day responders (1.9 ± 0.6 vs. 1.4 ± 0.5, Z = −2.31, p = 0.021) but not in headache day non-respond- ers (2.3 ± 0.9 vs. 2.0 ± 0.9, Z = −1.94, p = 0.052).

The percent reduction in headache days from T0 to T1 was again less strongly related to triptan efficacy ratings at T1 (H = 7.13, p = 0.068, rho = −0.38, p = 0.009). Discussion There are two main results to discuss.(1)The efficacy of triptans for treatment of acute migraine attacks before the first onabotulinumtoxinA treatment does not pre- dict the efficacy of onabotulinumtoxinA for the preventive treatment of chronic migraine.(2)There was an improvement in triptan efficacy in patients with a good response to the prophylaxis with onabotulinumtoxinA. Preventative treatment with onabotulinumtoxinA is often one of the later steps in the treatment algorithm for chronic migraine patients, and only part of the patients respond.

We could find no relation between triptan efficacy before onabotulinumtoxinA treatment and response to onabotulinumtoxinA treatment, despite using two differ- ent measures to quantify the response to onabotulinumtoxinA (efficacy rating and reduction of headache days per month).

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4 Treatment

Effect sizes of the (non-significant) relation between triptan efficacy at T0 and ona- botulinumtoxinA efficacy at T1 were very small (rho = 0.20), and effects of this size would not be deemed clinically significant or useful for prediction of treatment response.

Conclusions Response to triptans does not predict response to onabotulinumtoxinA in the treat- ment of chronic migraine.

Acknowledgement A machine generated summary based on the work of Eren, Ozan E.; Gaul, Charly; Peikert, Andreas; Gendolla, Astrid; Ruscheweyh, Ruth; Straube, Andreas. 2020 in Scientific Reports.

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