Does MIDAS reduction at 3 months predict the outcome of erenumab treatment? A real-world, open-label trial

Abstract

Background In Italy, monoclonal antibodies targeting the CGRP pathway are subsidized for the preventive treatment of high frequency and chronic migraine (CM) in patients with a MIgraine Disability ASsessment (MIDAS) score ≥ 11. Eligibility to treatment continuation requires a ≥ 50% MIDAS score reduction at three months (T3). In this study, we evaluate whether a ≥ 50% MIDAS score reduction at T3 is a reliable predictor of response to one-year erenumab treatment. Methods In this prospective, open-label, real-world study, 77 CM patients were treated with erenumab 70–140 mg s.c. every 28 days for one year (T13). We collected the following variables: monthly migraine days (MMDs), monthly headache days (MHDs), days of acute medication intake, MIDAS, HIT-6, anxiety, depression, quality of life and allodynia. Response to erenumab was evaluated as: i) average reduction in MMDs during the 1-year treatment period; and ii) percentage of patients with ≥ 50% reduction in MMDs during the last 4 weeks after the 13 th injection (Responders T13 ). Results Erenumab induced a sustained reduction in MMDs, MHDs and intake of acute medications across the 12-month treatment period, with 64.9% of patients qualifying as Responders T13 . At T3, 55.8% of patients reported a ≥ 50% reduction in MIDAS score (MIDAS Res ) and 55.4% of patients reported a ≥ 50% reduction in MMDs (MMD Res ). MIDAS Res and MMD Res patients showed a more pronounced reduction in MMDs during the 1-year treatment as compared to NON-MIDAS Res (MIDAS Res : T0: 23.5 ± 4.9 vs. T13: 7.7 ± 6.2; NON- MIDAS Res : T0: 21.6 ± 5.4 vs. T13: 11.3 ± 8.8, p = 0.045) and NON-MMD Res (MMD Res : T0: 23.0 ± 4.5 vs. T13: 6.6 ± 4.8; NON-MMD Res : T0: 22.3 ± 6.0 vs. T13: 12.7 ± 9.2, p < 0.001) groups. The percentage of Responders T13 did not differ between MIDAS Res (74.4%) and NON-MIDAS Res (52.9%) patients ( p = 0.058), while the percentage of Responders T13 was higher in the MMD Res group (83.3%) when compared to NON-MMD Res (42.9%) ( p = 0.001). MMD Res predicted the long-term outcome according to a multivariate analysis (Exp(B) = 7.128; p = 0.001), while MIDAS Res did not. Treatment discontinuation based on MIDAS Res would have early excluded 36.0% of Responders T13 . ...

Real-world experience with monthly and quarterly dosing of fremanezumab for the treatment of patients with migraine in Japan

“…This finding that at least one ≥50% response rate in any of months 1–3 could be a better predictor of favorable outcome at 6 months is very important to motivate patients to continue CGRP monoclonal antibodies in a clinical setting where the MMD value is susceptible to climate change, stress, and other factors depending on each patient. In line with our results, a long-term open-label study showed that a ≥ 50% reduction in MMDs at month 3 after initiation of erenumab treatment could predict 1-year outcome, but combinations of ≥50% response rates at 1–3 months were not evaluated ( 24 ).…”

Ten open questions in migraine prophylaxis with monoclonal antibodies blocking the calcitonin-gene related peptide pathway: a narrative review

“…Although with some discrepancies, positive post-hoc predictors of treatment success and treatment-induced changes associated with good outcome were also identified in real-world studies, most of them with erenumab (Table 1 ): headache unilaterality [ 52 , 53 ], cranial autonomic attack symptoms [ 54 ], higher baseline migraine frequency [ 51 , 55 ], less severe disability at baseline [ 34 , 55 ], absence of other primary headaches [ 28 , 56 ], good response to triptans [ 23 , 53 , 55 ], typical migraine features and vomiting [ 23 ], young age [ 36 ], and a 50% response after 3 months of treatment [ 57 ]. In experimental studies, responders to erenumab had higher susceptibility to attack induction by the intravenous administration of CGRP [ 58 ], higher pre-treatment salivary CGRP levels [ 59 ], increased thresholds of the biceps femoris withdrawal reflex at 3 months [ 60 ], lower serum CGRP levels at 4 weeks [ 61 ], and less iron accumulation in the periaqueductal gray and anterior cingulate cortex at 8 weeks post-injection [ 62 ].…”

“…In clinical practice very few patients may benefit from a switch to a 3rd anti-CGRP/rec mAb. If switching is considered after 12 weeks of treatment, a timepoint at which most patients will have responded or not [ 57 ], one has to take into account the recent results from an Italian registry showing that 146 out of 265 non-responders (55.1%) to an anti-CGRP/rec mAb at 12 weeks have nevertheless a 50% response after 24 weeks [ 71 ].…”

The first interim analysis of Italian patients enrolled in the real-world, Pan-European, prospective, observational, phase 4 PEARL study of fremanezumab effectiveness

“…Similarly, a long-term effectiveness study of three CGRP pathway mAbs found that ≥ 50% reduction in MIDAS score was achieved by 89.5% of patients compared with 36.4%–56.8% for MMD at Month 6, with authors concluding that the MIDAS score was the most advantageous efficacy scale in this setting [ 42 ]. In this context, however, a RWE study of 77 patients with CM treated with erenumab showed that a ≥ 50% reduction in MIDAS score at 3 months excluded more than one third of responders at Month 12, thus suggesting that the combined use of a reduction in MIDAS score and MMD could better reflect the proportion of patients who can benefit from treatment with CGRP pathway mAbs [ 43 ]. This discrepancy may be explained by the fact that MIDAS score indirectly reflects the intensity of migraine, while MMD reflect purely the number of days with migraine, regardless of their intensity [ 13 ].…”