A Scoping Review and Meta-Analysis of Anti-CGRP Monoclonal Antibodies: Predicting Response

Hong, Ja Bin; Lange, Kristin Sophie; Overeem, Lucas Hendrik; Triller, Paul; Raffaelli, Bianca; Reuter, Uwe

doi:10.3390/ph16070934

Cited by 26 publications

(14 citation statements)

References 106 publications

(293 reference statements)

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“…However, substantial inter-individual differences may occur. For instance, patients experiencing intense trigemino-vascular activation symptoms (such as unilateral pain, either alone or in association with UAS) appear to be particularly sensitive to anti-CGRP mAbs, exhibiting a notably rapid and high response rate, probably linked to the heightened sensitization of trigeminal nociceptors [ 9 , 13 ].…”

Section: Discussionmentioning

confidence: 99%

Ultra-late response (> 24 weeks) to anti-CGRP monoclonal antibodies in migraine: a multicenter, prospective, observational study

Barbanti,

Aurilia,

Egeo

et al. 2024

J Neurol

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Objective Nearly 60% of migraine patients treated with monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway experience a ≥ 50% reduction in monthly migraine days (MMD) at 12 weeks compared to baseline (responders). However, approximately half of the patients not responding to anti-CGRP mAbs ≤ 12 weeks do respond ≤ 24 weeks (late responders). We assessed frequency and characteristics of patients responding to anti-CGRP mAbs only > 24 weeks (ultra-late responders). Methods In this multicenter (n = 16), prospective, observational, real-life study, we enrolled all consecutive adults affected by high-frequency episodic migraine (HFEM: ≥ 8 days/month) or chronic migraine (CM), with ≥ 3 prior therapeutic failures, treated with any anti-CGRP mAbs for ≥ 48 weeks. We defined responders patients with a ≥ 50% response rate ≤ 12 weeks, late responders those with a ≥ 50% response rate ≤ 24 weeks, and ultra-late responders those achieving a ≥ 50% response only > 24 weeks. Results A total of 572 migraine patients completed ≥ 48 weeks of anti-CGRP mAbs treatment. Responders accounted for 60.5% (346/572), late responders for 15% (86/572), and ultra-late responders for 15.7% (90/572). Among ultra-late responders, 7.3% (42/572) maintained the ≥ 50% response rate across all subsequent time intervals (weeks 28, 32, 36, 40, 44, and 48) and were considered persistent ultra-late responders, while 8.4% (48/572) missed the ≥ 50% response rate at ≥ 1 subsequent time interval and were classified as fluctuating ultra-late responders. Fifty patients (8.7%) did not respond at any time interval ≤ 48 weeks. Ultra-late responders differed from responders for higher BMI (p = 0.033), longer duration of medication overuse (p < 0.001), lower NRS (p = 0.017) and HIT-6 scores (p = 0.002), higher frequency of dopaminergic symptoms (p = 0.002), less common unilateral pain—either alone (p = 0.010) or in combination with UAS (p = 0.023), allodynia (p = 0.043), or UAS and allodynia (p = 0.012)—a higher number of comorbidities (p = 0.012), psychiatric comorbidities (p = 0.010) and a higher proportion of patients with ≥ 1 comorbidity (p = 0.020). Conclusion Two-thirds of patients not responding to anti-CGRP mAbs ≤ 24 weeks do respond later, while non-responders ≤ 48 weeks are quite rare (8.7%). These findings suggest to rethink the duration of migraine prophylaxis and the definition of resistant and refractory migraine, currently based on the response after 2–3 months of treatment.

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Section: Discussionmentioning

confidence: 99%

Ultra-late response (> 24 weeks) to anti-CGRP monoclonal antibodies in migraine: a multicenter, prospective, observational study

Barbanti,

Aurilia,

Egeo

et al. 2024

J Neurol

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“…Attempts have been made to detect predictive factors for a positive therapeutic response to CGRP mAbs in the real-world setting [ 45 ]. We explored whether demographic and clinical parameters could predict the therapeutic response at V3.…”

Section: Discussionmentioning

confidence: 99%

Real-world experience with calcitonin gene-related peptide-targeted antibodies for migraine prevention: a retrospective observational cohort study at two Japanese headache centers

Shibata,

Fujita,

Hoshino

et al. 2024

BMC Neurol

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Background Although randomized controlled trials (RCTs) have shown that calcitonin gene-related peptide (CGRP)-targeted monoclonal antibodies (CGRP mAbs) are an efficacious and safe therapeutic modality for migraine prevention, their clinical benefits have not been well validated in Japanese patients in the real-world setting. The present study aimed to evaluate the real-world efficacy and safety of galcanezumab, fremanezumab, and erenumab in Japanese patients with migraine. Methods This observational retrospective cohort study was conducted at two headache centers in Japan. Patients with migraine who had experienced treatment failure with at least one traditional oral migraine preventive agent were treated with a CGRP mAb de novo. The primary efficacy endpoints were the changes from baseline in monthly migraine days (MMDs) and Headache Impact Test-6 (HIT-6) score after 3 dosing intervals (V3). We explored whether demographic and clinical characteristics predicted therapeutic outcomes at V3. Results Sixty-eight patients who completed three doses of a CGRP mAb (85.3% female [58/68], mean age: 46.2 ± 13.1 years) were included in the analysis. There were 19 patients with chronic migraine. The baseline MMDs were 13.4 ± 6.0. After 3 doses, the MMDs significantly decreased to 7.4 ± 5.5 (p < 0.0001), and the 50% response rate was 50.0%. HIT-6 score was significantly reduced from 66.7 ± 5.4 to 56.2 ± 8.7 after 3 doses (P = 0.0001). There was a positive correlation between the changes in MMDs and HIT-6 score from baseline after 2 doses (p = 0.0189). Those who achieved a ≥ 50% therapeutic response after the first and second doses were significantly more likely to do so at V3 (crude odds ratio: 3.474 [95% CI: 1.037 to 10.4], p = 0.0467). The most frequent adverse event was constipation (7.4%). None of the adverse events were serious, and there was no need for treatment discontinuation. Conclusions This real-world study demonstrated that CGRP mAbs conferred Japanese patients with efficacious and safe migraine prevention, and an initial positive therapeutic response was predictive of subsequent favorable outcomes. Concomitant measurement of MMDs and HIT-6 score was useful in evaluating the efficacy of CGRP mAbs in migraine prevention.

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“…We analysed the baseline characteristics of non-responders’, finding no statistically significant differences when compared to rest of the cohort. Since there are no predictors of response at present [ 30 , 31 ], our study provides the evidence that all patients can and should be treated. Moreover, the economic impact of people discontinuing the treatment is higher initially, but it will be mitigated by the time as only those patients who respond to anti-CGRP MAbs will continue the treatment.…”

Section: Discussionmentioning

confidence: 97%

Early and annual projected savings from anti-CGRP monoclonal antibodies in migraine prevention: a cost-benefit analysis in the working-age population

Lazaro-Hernandez,

Caronna,

Rosell-Mirmi

et al. 2024

J Headache Pain

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Background Migraine is one of the main causes of disability worldwide. Anti-CGRP monoclonal antibodies (MAbs) have proven to be safe and efficacious as preventive migraine treatments. However, their use is restricted in many countries due to their apparently high cost. Cost-benefit studies are needed. Objective To study the cost-benefit of anti-CGRP MAbs in working-age patients with migraine. Methods This is a prospective cohort study of consecutive migraine patients treated with anti-CGRP MAbs (erenumab, fremanezumab and galcanezumab) following National reimbursement policy in a specialized headache clinic. Migraine characteristics and the work impact scale (WPAI) were compared between baseline (M0) and after 3 (M3) and 6 months (M6) of treatment. Using WPAI and the municipal average hourly wage, we calculated indirect costs (absenteeism and presenteeism) at each time point. Direct costs (emergency visits, acute medication use) were also analysed. A cost-benefit study was performed considering the different costs and savings of treating with MAbs. Based on these data an annual projection was conducted. Results From 256 treated working-age patients, 148 were employed (89.2% women; mean age 48.0 ± 8.5 years), of which 41.2% (61/148) were responders (> 50% reduction in monthly headache days (MHD)). Statistically significant reductions between M0 and M3/M6 were found in absenteeism (p < 0.001) and presenteeism (p < 0.001). Average savings in indirect costs per patient at M3 were absenteeism 105.4 euros/month and presenteeism 394.3 euros/month, similar for M6. Considering the monthly cost of anti-CGRP MAbs, the cost-benefit analysis showed savings of 159.8 euros per patient at M3, with an annual projected savings of 639.2 euros/patient. Both responders and partial responders (30–50% reduction in MHD) presented a positive cost-benefit balance. The overall savings of the cohort at M3/M6 compensated the negative cost-benefit balance for non-responders (< 30% reduction in MHD). Conclusion Anti-CGRP MAbs have a positive impact in the workforce significantly reducing absenteeism and presenteeism. In Spain, this benefit overcomes the expenses derived from their use already at 3 months and is potentially sustainable at longer term; also in patients who are only partial responders, prompting reconsideration of current reimbursement criteria and motivating the extension of similar cost-benefit studies in other countries.

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A Scoping Review and Meta-Analysis of Anti-CGRP Monoclonal Antibodies: Predicting Response

Cited by 26 publications

References 106 publications

Ultra-late response (> 24 weeks) to anti-CGRP monoclonal antibodies in migraine: a multicenter, prospective, observational study

Ultra-late response (> 24 weeks) to anti-CGRP monoclonal antibodies in migraine: a multicenter, prospective, observational study

Real-world experience with calcitonin gene-related peptide-targeted antibodies for migraine prevention: a retrospective observational cohort study at two Japanese headache centers

Early and annual projected savings from anti-CGRP monoclonal antibodies in migraine prevention: a cost-benefit analysis in the working-age population

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