Discontinuing monoclonal antibodies targeting CGRP pathway after one-year treatment: an observational longitudinal cohort study

Abstract Background Monoclonal antibodies anti-calcitonin gene-related peptide (mAbs anti-CGRP) pathway are effective and safe on migraine prevention. However, some drug agencies limited these treatments to one year due to their high costs. This study aimed at evaluating the effect of discontinuing mAbs anti-CGRP on monthly migraine days (MMDs) and disability in high-frequency episodic (HFEM) and chronic migraine (CM) patients. Methods This observational longitudinal cohort study was conducted at 10 Italian headache centres. Consecutive adult patients were followed-up for three months (F-UP1–3) after discontinuation of a one-year erenumab/galcanezumab treatment. The primary endpoint was the change in F-UP MMDs. Secondary endpoints included variation in pain intensity (Numerical Rating Scale, NRS), monthly acute medication intake (MAMI), and HIT-6 scores. We also assessed from F-UP1 to 3 the ≥50% response rate, relapse rate to CM, and recurrence of Medication Overuse (MO). Results We enrolled 154 patients (72.1% female, 48.2 ± 11.1 years, 107 CM, 47 HFEM); 91 were treated with erenumab, 63 with galcanezumab. From F-UP1 to F-UP3, MMDs, MAMI, NRS, and HIT-6 progressively increased but were still lower at F-UP3 than baseline (Friedman’s analysis of rank, p < .001). In the F-UP1–3 visits, ≥50% response rate frequency did not differ significantly between CM and HFEM patients. However, the median reduction in response rate at F-UP3 was higher in HFEM (− 47.7% [25th, − 79.5; 75th,-17.0]) than in CM patients (− 25.5% [25th, − 47.1; 75th, − 3.3]; Mann-Whitney U test; p = .032). Of the 84 baseline CM patients who had reverted to episodic migraine, 28 (33.3%) relapsed to CM at F-UP1, 35 (41.7%) at F-UP2, 39 (46.4%) at F-UP3. Of the 64 baseline patients suffering of medication overuse headache ceasing MO, 15 (18.3%) relapsed to MO at F-UP1, 26 (31.6%) at F-UP2, and 30 (42.3%, 11 missing data) at F-UP3. Lower MMDs, MAMI, NRS, and HIT-6 and higher response rate in the last month of therapy characterized patients with ≥50% response rate at F-UP1 and F-UP3 (Mann-Whitney U test; consistently p < .01). Conclusion Migraine frequency and disability gradually increased after mAbs anti-CGRP interruption. Most patients did not relapse to MO or CM despite the increase in MMDs. Our data suggest to reconsider mAbs anti-CGRP discontinuation.

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Discontinuing Monoclonal Antibodies Targeting CGRP Pathway After One-Year Treatment: An Observational Longitudinal Cohort Study

10.21203/rs.3.rs-1047534/v1 ◽

2021 ◽

Author(s):

Fabrizio Vernieri ◽

Nicoletta Brunelli ◽

Roberta Messina ◽

Carmelina Maria Costa ◽

Bruno Colombo ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Cohort Study ◽

Rating Scale ◽

Numerical Rating Scale ◽

Longitudinal Cohort Study ◽

Longitudinal Cohort ◽

Calcitonin Gene ◽

Numerical Rating ◽

Secondary Endpoints ◽

One Year

Abstract Background: The monoclonal antibodies anti-calcitonin gene-related peptide (mAbs anti-CGRP) pathway revolutionized migraine prevention. However, some drug agencies limited the treatment to one year due to their high costs. This study aimed at evaluating the effect of discontinuing mAbs anti-CGRP on monthly migraine days (MMDs) and disability in high-frequency episodic (HFEM) and chronic migraine (CM) patients. Methods: This observational longitudinal cohort study was conducted at 10 Italian headache centres (November 2019-July 2021). Consecutive adult patients followed up for three months (F-UP1-3) after discontinuation of a one-year erenumab/galcanezumab treatment were enrolled. The primary endpoint was the change in F-UP MMDs. Secondary endpoints included variation in pain intensity (Numerical Rating Scale, NRS), monthly painkiller intake (MPI), and HIT-6 scores. We also assessed from F-UP1 to 3 the ≥50% response rates (RR), relapse rate to CM, and recurrence of Medication Overuse (MO).Results: We enrolled 154 patients (72.1% female, 48.2±11.1 years, 107 CM, 47 HFEM); 91 were treated with erenumab, 63 with galcanezumab. From F-UP1 to F-UP3, MMDs, MPI, NRS, and HIT-6 progressively increased but were still lower at F-UP 3 than baseline (Friedman's analysis of rank, p<.001). In the F-UP 1-3 visits, ≥50%RR frequency did not differ significantly between CM and HFEM patients. However, the median reduction in RR at F-UP3 was higher in HFEM (-47.7% [25th, -79.5; 75th ,-17.0]) than in CM patients (-25.5% [25th, -47.1; 75th ,-3.3]; Mann-Whitney U test; p=.032). Of the 84 baseline CM patients who had reverted to EM, 28 (33.3%) relapsed to CM at F-UP1, 35 (41.7)% at F-UP2, 39 (46.4%) at F-UP3. Of the 64 baseline MO patients ceasing MO, 15 (18.3%) relapsed to MO at F-UP1, 26 (31.6%) at F-UP2, and 30 (42.3%, 11 missing data) at F-UP3. Lower MMDs, MPI, NRS, and HIT-6 and higher RR in the last month of therapy characterized patients with 50% RR at F-UP1 and F-UP3 (Mann-Whitney U test; consistently p<.01).Conclusion: Migraine frequency and disability gradually increased after anti-CGRP mAbs interruption. Most patients did not relapse to MO or CM despite the increase in MMDs. Our data suggest to reconsider mAbs anti-CGRP discontinuation.

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Long-term predictors of remission in patients treated for medication-overuse headache at a specialized headache center: A prospective cohort study

Cephalalgia ◽

10.1177/0333102416683918 ◽

2016 ◽

Vol 38 (2) ◽

pp. 265-273 ◽

Cited By ~ 9

Author(s):

Jasna J Zidverc-Trajkovic ◽

Tatjana Pekmezovic ◽

Zagorka Jovanovic ◽

Aleksandra Pavlovic ◽

Milija Mijajlovic ◽

...

Keyword(s):

Cohort Study ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Medication Overuse ◽

Medication Overuse Headache ◽

Predictive Values ◽

One Year ◽

The One

Objective To evaluate long-term predictors of remission in patients with medication-overuse headache (MOH) by prospective cohort study. Background Knowledge regarding long-term predictors of MOH outcome is limited. Methods Two hundred and forty MOH patients recruited from 2000 to 2005 were included in a one-year follow-up study and then subsequently followed until 31 December 2013. The median follow-up was three years (interquartile range, three years). Predictive values of selected variables were assessed by the Cox proportional hazard regression model. Results At the end of follow-up, 102 (42.5%) patients were in remission. The most important predictors of remission were lower number of headache days per month before the one-year follow-up (HR-hazard ratio = 0.936, 95% confidence interval (CI) 0.884–0.990, p = 0.021) and efficient initial drug withdrawal (HR = 0.136, 95% CI 0.042–0.444, p = 0.001). Refractory MOH was observed in seven (2.9%) and MOH relapse in 131 patients (54.6%). Conclusions Outcome at the one-year follow-up is a reliable predictor of MOH long-term remission.

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Are asymptomatic ultrasound abnormalities in the achilles tendon of elite soccer players risk factors for symptoms one year later? a longitudinal cohort study

British Journal of Sports Medicine ◽

10.1136/bjsm.2010.081554.21 ◽

2011 ◽

Vol 45 (2) ◽

pp. e1-e1

Author(s):

S. Jhingan ◽

M. Perry ◽

G. O'Driscoll ◽

M. Ahmad ◽

N. Maffulli ◽

...

Keyword(s):

Risk Factors ◽

Cohort Study ◽

Achilles Tendon ◽

Soccer Players ◽

Longitudinal Cohort Study ◽

Longitudinal Cohort ◽

One Year

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Remission of chronic headache: An 11-year follow-up study. Data from the Nord-Trøndelag Health Surveys 1995–1997 and 2006–2008

Cephalalgia ◽

10.1177/0333102418769940 ◽

2018 ◽

Vol 38 (14) ◽

pp. 2026-2034 ◽

Cited By ~ 2

Author(s):

Knut Hagen ◽

Espen Saxhaug Kristoffersen ◽

Bendik Slagvold Winsvold ◽

Lars Jacob Stovner ◽

John-Anker Zwart

Keyword(s):

Cohort Study ◽

Chronic Headache ◽

Response Rate ◽

Medication Overuse ◽

Medication Overuse Headache ◽

Population Based ◽

Study Data ◽

Health Study ◽

Musculoskeletal Complaints

Objectives To estimate remission rates of chronic headache and predictors of remission. Methods In this longitudinal population-based cohort study, we used validated headache questionnaire data from the second (1995–1997, baseline; n = 51,856 aged ≥ 20 years, response rate: 55%) and third wave (2006–2008, follow-up, response rate: 42%) of the Nord-Trøndelag Health Study. Chronic headache was defined as ≥15 headache days/month during the last year. Chronic headache remission was defined as headache less than 15 days/month at follow-up. Potential predictors of remission were evaluated using logistic regression. Results At baseline, 1266 (2.4%) participants reported chronic headache. Of these, 605 (48%) answered headache questions at follow-up. Remission was observed in 452 (74.7%), the proportion being almost identical in men and women (74.4% vs. 74.9, p = 0.92). In analyses adjusting for age, gender and education level, remission at follow-up was more than two times more likely among individuals without medication overuse headache (OR = 2.4, 95% CI 1.7–3.6) and without chronic musculoskeletal complaints (OR = 2.9, 95% CI 1.5–5.0) at baseline. Conclusions In this longitudinal population-based cohort study, three-quarters of chronic headache participants remitted from chronic headache. Remission was associated with no medication overuse headache and no chronic musculoskeletal complaints at baseline.

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Cochrane systematic review and meta-analysis of botulinum toxin for the prevention of migraine

BMJ Open ◽

10.1136/bmjopen-2018-027953 ◽

2019 ◽

Vol 9 (7) ◽

pp. e027953 ◽

Cited By ~ 12

Author(s):

Clare P Herd ◽

Claire L Tomlinson ◽

Caroline Rick ◽

William J Scotton ◽

Julie Edwards ◽

...

Keyword(s):

Systematic Review ◽

Botulinum Toxin ◽

Relative Risk ◽

Rating Scale ◽

Treatment Time ◽

Medication Overuse ◽

Numerical Rating Scale ◽

Meta Analysis ◽

Medication Overuse Headache ◽

Episodic Migraine

ObjectivesTo assess the effects of botulinum toxin for prevention of migraine in adults.DesignSystematic review and meta-analysis.Data sourcesCENTRAL, MEDLINE, Embase and trial registries.Eligibility criteriaWe included randomised controlled trials (RCTs) of botulinum toxin compared with placebo, active treatment or clinically relevant different dose for adults with chronic or episodic migraine, with or without the additional diagnosis of medication overuse headache.Data extraction and synthesisCochrane methods were used to review double-blind RCTs. Twelve week post-treatment time-point data was analysed.ResultsTwenty-eight trials (n=4190) were included. Trial quality was mixed. Botulinum toxin treatment resulted in reduced frequency of −2.0 migraine days/month (95% CI −2.8 to −1.1, n=1384) in chronic migraineurs compared with placebo. An improvement was seen in migraine severity, measured on a numerical rating scale 0 to 10 with 10 being maximal pain, of −2.70 cm (95% CI −3.31 to −2.09, n=75) and −4.9 cm (95% CI −6.56 to −3.24, n=32) for chronic and episodic migraine respectively. Botulinum toxin had a relative risk of treatment related adverse events twice that of placebo, but a reduced risk compared with active comparators (relative risk 0.76, 95% CI 0.59 to 0.98) and a low withdrawal rate (3%). Although individual trials reported non-inferiority to oral treatments, insufficient data were available for meta-analysis of effectiveness outcomes.ConclusionsIn chronic migraine, botulinum toxin reduces migraine frequency by 2 days/month and has a favourable safety profile. Inclusion of medication overuse headache does not preclude its effectiveness. Evidence to support or refute efficacy in episodic migraine was not identified.

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