Evaluation of the concomitant use of prophylactic treatments in patients with migraine under anti-calcitonin gene-related peptide therapies: The PREVENAC study.

BACKGROUND AND PURPOSE: Anti-calcitonin gene-related peptide (CGRP) therapies are recent preventive therapies approved for both episodic and chronic migraine. One of the measures of effectiveness is the withdrawal of other preventive treatments. The objective of this study is to quantify the impact of anti-CGRP drugs in concomitant preventive treatment in patients with migraine. METHODS: This was an observational, retrospective, multicenter cohort study with patients from nine national headache units. Patients with migraine undergoing treatment for at least 6 months with anti-CGRP antibodies, who were initially associated with some preventive treatment (oral and/or onabotulinumtoxinA) were included. Demographic and clinical variables were collected, as well as variables related to headache. Differences according to withdrawal or nonwithdrawal were evaluated. RESULTS: A total of 408 patients were included, 86.52% women, 48.79 (SD = 1.46) years old. Preventive treatment was withdrawn in 43.87% (179/408), 20.83% partially and 23.04% totally. In 27.45% (112/408), it was maintained exclusively due to comorbidity and in 28.6% (117/408) due to partial efficacy. The most frequent time of withdrawal was between 3 and 5 months after the start of treatment. The baseline characteristics associated with nonwithdrawal were comorbidities: insomnia, hypertension and obesity, chronic migraine, and medication overuse. In the multivariate analysis, the absence of high blood pressure, a greater number of preventive treatments at the start, and a lower number of migraine days/month after anti-CGRP treatment were independently associated with withdrawal of the treatment (p < 0.05). CONCLUSIONS: Anti-CGRP antibodies allow the withdrawal of associated preventive treatment in a significant percentage of patients, which supports its effectiveness in real-life conditions.

Effectiveness, tolerability, and response predictors of preventive anti-CGRP mAbs for migraine in patients over 65 years old: a multicenter real-world case-control study.

OBJECTIVE: To evaluate clinical characteristics, effectiveness, and tolerability of preventive anti- calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) in the elderly. Anti-CGRP mAbs have demonstrated efficacy and safety in patients with migraine although there is limited information regarding the elderly. DESIGN: We performed a multicenter case-control study of cases (patients over 65 years old) and controls (sex-matched patients under 55 years old) with migraine receiving anti-CGRP mAbs. METHODS: We included the demographic characteristics, effectiveness-reduction in the number of monthly headache days (MHD) and monthly migraine days (MMD), 30%, 50%, and 75% responder rates-and treatment emergent adverse events (TEAEs). The primary endpoint was the 50% response rate regarding MHD at weeks 20-24; exploratory 50% response predictors in the elderly were evaluated. RESULTS: In total, 228 patients were included: 114 cases , 114 controls-. Among cases 84.2% (96/114) were women, 79.8% (91/114) CM; mean age of cases 70.1 years old (range: 66-86); mean age of controls was 42.9 years old(range: 38-49). Cases had a higher percentage of vascular risk factors (P < .05),older age of onset (P < .001) and more reported prior preventive treatments (P < .001). Regarding effectiveness in cases, 50% response rate was achieved by 57.5% (42/73) at 20-24 weeks, with lower reduction in the MHD at 8-12 weeks (5 [7.2], 8 [9.1]; P = .001) and a higher reduction in MMD at 20-24 weeks (10.7 [9.1], 9.2 [7.7]; P = .04) compared to the control group. The percentage of TEAEs was similar in the 2 groups. Diagnosis of episodic migraine (EM) (P = .03) and lower number of MHD at baseline (P = .001) were associated with a 50% response in the elderly in univariate analysis. CONCLUSIONS: Our study provides real world evidence of effectiveness and safety of anti-CGRP mAbs for migraine in patients without upper age-limit and possible predictors of anti-CGRP response in the elderly.

Machine-learning-based approach for predicting response to anti-calcitonin gene-related peptide (CGRP) receptor or ligand antibody treatment in patients with migraine: A multicenter Spanish study.

BACKGROUND AND PURPOSE: Several variables have been reported to be associated with anti-calcitonin gene-related peptide (CGRP) receptor or ligand antibody response, but with differing results. Our objective was to determine whether machine-learning (ML)-based models can predict 6-, 9- and 12-month responses to anti-CGRP receptor or ligand therapies among migraine patients. METHODS: We performed a multicenter analysis of prospectively collected data from patients with migraine receiving anti-CGRP therapies. Demographic and clinical variables were collected. Response rates in the 30% to 50% range, or at least 30%, in the 50% to 75% range, or at least 50%, and response rate of at least 75% regarding the reduction in the number of headache days per month at 6, 9 and 12 months were calculated. A sequential forward feature selector was used for variable selection and ML-based predictive models for the response to anti-CGRP therapies at 6, 9 and 12 months, with model accuracy not less than 70%, were generated. RESULTS: A total of 712 patients were included, 93% were women, and the mean (SD) age was 48 (11.6) years. Eighty-four percent of patients had chronic migraine. ML-based models using headache days/month, migraine days/month and the Headache Impact Test (HIT-6) yielded predictions with an F1 score range of 0.70-0.97 and an area under the receiver-operating curve score range of 0.87-0.98. SHAP (SHapley Additive exPlanations) summary plots and dependence plots were generated to evaluate the relevance of the factors associated with the prediction of the above-mentioned response rates. CONCLUSIONS: Our results show that ML models can predict anti-CGRP response at 6, 9 and 12 months. This study provides a predictive tool that can be used in a real-world setting.

MAB-MIG: registry of the spanish neurological society of erenumab for migraine prevention.

BACKGROUND: Erenumab was approved in Europe for migraine prevention in patients with ≥ 4 monthly migraine days (MMDs). In Spain, Novartis started a personalized managed access program, which allowed free access to erenumab before official reimbursement. The Spanish Neurological Society started a prospective registry to evaluate real-world effectiveness and tolerability, and all Spanish headache experts were invited to participate. We present their first results. METHODS: Patients fulfilled the ICHD-3 criteria for migraine and had ≥ 4 MMDs. Sociodemographic and clinical data were registered as well as MMDs, monthly headache days, MHDs, prior and concomitant preventive treatment, medication overuse headache (MOH), migraine evolution, adverse events, and patient-reported outcomes (PROs): headache impact test (HIT-6), migraine disability assessment questionnaire (MIDAS), and patient global improvement change (PGIC). A > 50% reduction of MMDs after 12 weeks was considered as a response. RESULTS: We included 210 patients (female 86.7%, mean age 46.4 years old) from 22 Spanish hospitals from February 2019 to June 2020. Most patients (89.5%) suffered from chronic migraine with a mean evolution of 8.6 years. MOH was present in 70% of patients, and 17.1% had migraine with aura. Patients had failed a mean of 7.8 preventive treatments at baseline (botulinum toxin type A-BoNT/A-had been used by 95.2% of patients). Most patients (67.6%) started with erenumab 70 mg. Sixty-one percent of patients were also simultaneously taking oral preventive drugs and 27.6% were getting simultaneous BoNT/A. Responder rate was 37.1% and the mean reduction of MMDs and MHDs was -6.28 and -8.6, respectively. Changes in PROs were: MIDAS: -35 points, HIT-6: -11.6 points, PIGC: 4.7 points. Predictors of good response were prior HIT-6 score < 80 points (p = 0.01), ≤ 5 prior preventive treatment failures (p = 0.026), absence of MOH (p = 0.039), and simultaneous BoNT/A treatment (p < 0.001). Twenty percent of patients had an adverse event, but only two of them were severe (0.9%), which led to treatment discontinuation. Mild constipation was the most frequent adverse event (8.1%). CONCLUSIONS: In real-life, in a personalized managed access program, erenumab shows a good effectiveness profile and an excellent tolerability in migraine prevention in our cohort of refractory patients.

Detection of potential risks in the prescription of tricyclic antidepressants through an online clinical alert system.

OBJECTIVE: To analyse the use, indications and potential risks of tricyclic antidepressants (TCAs), using a technological system of clinical alerts at the time of prescription. METHODS: Observational, descriptive, retrospective study on a population covered by a Colombian health insurance plan with an average of 2,333,582 members/month. The information was generated in the PBM (Pharmacy Benefit Management) MC21 Colombia technological platform. RESULTS: Of the total members, 368,298 (16%) patients/month on average were prescribed medicines; 3,640 (1%) were prescribed TCAs: 2,573 amitriptyline (70%) and 1.062 imipramine (29%); 817 (22.5%) were over 65 years of age. The median daily dose of amitriptyline and imipramine was 25 mg. A total of 17,153 alerts were reported: 8,685 (51%) for drug-drug interactions, 7,354 (43%) for drug-age interactions and 543 (3%) for duplicate therapy. CONCLUSIONS: Risks were identified in the prescription of tricyclic antidepressants, especially in the over-65 population, where these drugs are used in particular for the management of neuropathic pain. The clinical alert system at the time of medicinal product formulation can make an important contribution to the prevention of potential adverse events associated with the use of medicinal products.

Self-reported periodontitis and migraine: results from a multicenter, cross-sectional survey in Spain.

The aim of this study was to evaluate self-reported periodontitis (PD) prevalence in migraineurs as well as to investigate the association between both diseases. A cross-sectional survey was carried out including patients diagnosed with migraine attending 12 Spanish Headache Units. We determined diagnosis of PD administering a validated self-reported questionnaire. Socio-demographic, clinical and medical information, comorbidities, daily habits, migraine characteristics and medication were collected using a questionnaire. Of the 651 consecutive migraineurs included in the study, 393 suffered from chronic migraine (CM). Self-reported PD was detected in 327 patients with migraine (50.2%). Migraineurs with self-reported PD were significantly older and had a previous history of fibromyalgia, stress, anxiety, depression, and allodynia (all P < 0.001). Additionally, this group of patients consumed more topiramate (P = 0.008) and simple analgesics (P < 0.001) than patients with migraine and without self-reported PD. Also, they were less active physically and belonged to a low education level (both P < 0.001). Prevalence of self-reported PD was significantly higher in chronic migraineurs compared to those diagnosed with episodic migraine (EM) (53.9% vs. 44.6%, P = 0.019). Logistic regression analyses showed that self-reported PD was associated with CM (OR 1.456; 95% CI 1.062-1.997, P = 0.020). However, after adjusting for significant confounders, the association was attenuated (OR 1.100; 95% CI 0.784-1.543, P = 0.581). We concluded that self-reported PD was significantly more frequent in CM compared to EM. Self-reported PD was associated with the presence of CM, although some comorbidities shared by both diseases could have an effect on this association.