Discussion
The results of the present study show that patients with
difficult-to-treat episodic or chronic migraine, who previously did not
respond to up to three pharmacological classes of migraine preventive
medication (being onabotulinumtoxinA one of these options for CM
patients), can still achieve a clinically significant improvement with
erenumab or galcanezumab.
This observation is supported by the following findings: (i) MHD were
significantly reduced after administering 3 or 6 doses of erenumab or
galcanezumab, independently if the patients were diagnosed with EM or
CM; (ii) AMSMD were also diminished with both CGRP MoAbs after 3 or 6
doses, despite the diagnose; (iii) erenumab and galcanezumab reduced the
scores obtained in three different PROMs for migraine and pain
assessment: HIT-6, MIDAS and VAS, in all the groups included in the
study.
MHD and AMSMD are common objective parameters employed to evaluate CGRP
MoAbs efficacy in CTs and effectiveness in real-world studies11-13,22,27. In this regard, a marked significant
reduction in MHD was observed, which already implies a marked
improvement in patients’ life quality. On top of that, a remarkable
effect was also observed on AMSMD, which were reduced by a half in, at
least, a 50% of the patients enrolled in each of the groups of the
study. This outcome is of great interest since a response rate of ≥ 50%
reduction in medication use from baseline is often used as a clinically
significant threshold for patients suffering from migraine28 and agrees with previous results obtained from
real-world observational studies.
Albeit the authors are aware that PROMs for assessing the impact of
headaches and the outcomes of treatment have several limitations, an
individual’s self-report of the presence, severity, frequency, and
impact of headache is crucial to understanding the effectiveness of
therapeutic interventions 29, especially considering
that about 45% of the patients with migraine oral preventive therapies
discontinue treatment because no improvement is perceived30. Therefore, HIT-6, one of the most reliable and
valid tests available for migraine assessment 29, and
MIDAS, the most commonly used PROM in phase 3 CTs for both drugs, were
employed in the present study 11,16,31.
Both CGRP MoAbs significantly reduced the scores obtained in the HIT-6
tool, meaning that erenumab and galcanezumab successfully diminish the
impact of migraine in patients’ quality of life. Interestingly, MIDAS
reduction after the administration of 3 doses of either erenumab or
galcanezumab observed in this study was substantially greater than the
reported in CTs for CM and EM 11,12,16,31,32, fact
that supports the need of conducting observational studies in which
patients with more complexity (polypharmacy, concomitant preventive
treatments, previous treatment failures) are included. Additionally, a
significant reduction in VAS was reported for both drugs regardless the
diagnose. This result concurs with recent published data for erenumab33, yet, to our knowledge, it is the first time
evaluated for galcanezumab (CM and EM). Altogether, these data, though
limitedly, may suggest that both CGRP MoAbs are able to not only
diminish frequency, but also migraine intensity, yet further studies are
required to verify this assumption.
Furthermore, safety profile was also addressed for this work since CTs
are typically designed to focus on efficacy endpoints rather than
adverse event endpoints. Consequently, these studies are often
underpowered to detect adverse events compared to follow-up in clinical
practice 34. Here, the most frequent adverse event
reported for both CGRP MoAbs was mild-to-moderate constipation (14-18%
of the patients), as reported in other real-life studies20,33,35 and higher than registered in CTs11-13, yet no patient had to stop treatment due to
this cause. These data are compelling, notably when around 40-70% of
patients taking any oral preventive medication for migraine discontinue
treatment because of drug-related adverse events30,36,37. However, these safety results should be
interpreted with caution because though only 1 (1,2%) patient treated
with erenumab and 1 (1,79%) with galcanezumab had to discontinue
treatment due to drug related adverse events, these were severe.
Another aspect that needs to be mentioned is that other authors report
even higher adverse event frequencies of mild to moderate adverse events
(≈70%) in real-world observational studies 20. These
findings indicate nothing but the urging need of designing more
real-world observational studies in which safety is properly addressed,
especially in long-term exposure (more than 12 months), young and
elderly populations.
Besides, other questions regarding effectiveness and safety of CGRP
MoAbs still require answers, namely, may switching from one to another
be useful in non-responders? May this compromise effectiveness by
propitiating wearing-off effects? Could this trigger a higher incidence
of adverse event? Questions that will require multidisciplinary teams to
properly cover healthcare provided for patients with rigor and seek for
structured data that could improve the health outcomes pursued.