In our real-life cohort of chronic migraine patients with MO, demographic data and baseline headache characteristics were similar to clinical trials [8,9,10], with the exception of longer disease duration and more refractoriness to preventive medication, in line with other real-world studies [4,5,6,7].
In this prospective study, after 6 months of treatment with anti-CGRP MAbs, we observed that:
First, ≥50% reduction in headache frequency for both MDM and HDM is similar regardless of the presence of MO at baseline. Our results are in line with other real-world multicenter CM cohorts for both erenumab (at 3 and 6 months) [4, 7] and galcanezumab (at 6 months) , all of which are higher than the reponse seen in clinical trials [13,14,15]. Moreover, patients with ongoing MO after 6 months do experience reduction in headache frequency similar to trials  and improve acute medication intake although not reaching a non-overuse behavior. This points out to the fact that anti-CGRP MAbs may be an effective preventive treatment for refractory migraine patients with MO. According to our results, they are also safe and well-tolerated.
Second, 60.6% of patients achieve remission of MO. This rate is comparable to the one observed by Ornello et al.  for erenumab (71.9%) but slightly lower than the one showed for galcanezumab in the GARLIT study (82.0%) . The reason may be due to how MO remission was defined in our study as an absence of MO during 6-months of treatment and not only at one specific timepoint (6 months). However, our results are still better than the ones seen in clinical trials ; justifying the use in daily practice of anti-CGRP MAbs to facilitate acute medication discontinuation through their preventive effect.
Third, anti-CGRP MAbs help categorize MO into two profiles: 1) the MO-resolution group which represents patients whose overuse is directly related to migraine frequency, reducing days of acute medication intake by improving frequency with treatment; 2) the MO-ongoing group that includes patients where, despite a reduction in MDM, other factors such as higher pain intensity possibly prevent from achieving a non-overuse behavior. This may explain our finding of pain intensity as an independent factor of MO resolution. In this regard, pain severity may be seen as an expression of a worse basal disease phenotype leading to medication overuse rather than representing the consequence of it. More severe pain may lead to a greater analgesic intake even within a single headache day or use of benzodiazepine for pain relief. It is not surprising that these two factors were associated with ongoing MO, having these patients a significantly more severe headpain at baseline compared to the one the MO-resolution group had. However, these MO profiles and possible predictors of MO resolution should be further evaluated by long-term real-life studies and larger cohorts of treated patients with anti-CGRP MAbs.
Finally, neither the specific type of anti-CGRP MAbs (erenumab vs. galcanezumab) used, nor the presence of concomitant treatment with BTX-A could be considered as predictors of MO resolution. These findings have important implications in daily practice as they do not support (1) one anti-CGRP MAb being better than the other for MO patients and (2) using dual therapy with concomitant BTX-A instead of monotherapy.
The major limitation of this study is the presence of concomitant preventive treatments that make it difficult to exclusively evaluate the effect of anti-CGRP MAbs. However, this is a common bias in all real-life studies which we tried to reduce by keeping patients on stable doses of concomitant preventives.
Our real-life study therefore supports the use of anti-CGRP drugs in patients with chronic migraine and MO with similar results as compared to those who do not overuse. Moreover, the preventive effect of anti-CGRP monoclonal antibodies facilitates acute medication discontinuation and achieves reduction in headache frequency and acute medication use days regardless of patients stopping overuse.