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Open Access 01-12-2021 | Migraine | Research article

Galcanezumab for the prevention of high frequency episodic and chronic migraine in real life in Italy: a multicenter prospective cohort study (the GARLIT study)

Authors: Fabrizio Vernieri, Claudia Altamura, Nicoletta Brunelli, Carmelina Maria Costa, Cinzia Aurilia, Gabriella Egeo, Luisa Fofi, Valentina Favoni, Giulia Pierangeli, Carlo Lovati, Marco Aguggia, Florindo d’Onofrio, Alberto Doretti, Paola Di Fiore, Cinzia Finocchi, Renata Rao, Francesco Bono, Angelo Ranieri, Maria Albanese, Sabina Cevoli, Piero Barbanti, for the GARLIT Study Group

Published in: The Journal of Headache and Pain | Issue 1/2021

Abstract

Background

The clinical benefit of galcanezumab, demonstrated in randomized clinical trials (RCTs), remains to be quantified in real life. This study aimed at evaluating the effectiveness, safety and tolerability of galcanezumab in the prevention of high-frequency episodic migraine (HFEM) and chronic migraine (CM) in a real-life setting.

Methods

This multicenter prospective observational cohort study was conducted between November 2019 and January 2021 at 13 Italian headache centers. Consecutive adult HFEM and CM patients clinically eligible were enrolled and treated with galcanezumab subcutaneous injection 120 mg monthly with the first loading dose of 240 mg. The primary endpoint was the change in monthly migraine days (MMDs) in HFEM and monthly headache days (MHDs) in CM patients after 6 months of therapy (V6). Secondary endpoints were the Numerical Rating Scale (NRS), monthly painkiller intake (MPI), HIT-6 and MIDAS scores changes, ≥50% responder rates (RR), the conversion rate from CM to episodic migraine (EM) and Medication Overuse (MO) discontinuation.

Results

One hundred sixty-three patients (80.5% female, 47.1 ± 11.7 years, 79.8% CM) were included. At V6, MMDs reduced by 8 days in HFEM and MHDs by 13 days in CM patients (both p < .001). NRS, MPI, HIT-6 and MIDAS scores significantly decreased (p < .001). Ten patients (6.1%) dropped out for inefficacy and classified as non-responders. Patients with ≥50%RRs, i.e. responders, were 76.5% in the HFEM and 63.5% in the CM group at V6. Among CM patients, the V6 responders presented a lower body mass index (p = .018) and had failed a lower number of preventive treatments (p = .013) than non-responders. At V6, 77.2% of CM patients converted to EM, and 82.0% ceased MO. Adverse events, none serious, were reported in up to 10.3% of patients during evaluation times.

Conclusions

Galcanezumab in real life was safe, well tolerated and seemed more effective than in RCTs. Normal weight and a low number of failed preventives were positively associated with galcanezumab effectiveness in CM patients.

Trial registration

ClinicalTrials.govNCT04803513.

Stovner LJ, Nichols E, Steiner TJ, Abd-Allah F, Abdelalim A, al-Raddadi RM, Ansha MG, Barac A, Bensenor IM, Doan LP, Edessa D, Endres M, Foreman KJ, Gankpe FG, Gopalkrishna G, Goulart AC, Gupta R, Hankey GJ, Hay SI, Hegazy MI, Hilawe EH, Kasaeian A, Kassa DH, Khalil I, Khang YH, Khubchandan J, Kim YJ, Kokubo Y, Mohammed MA, Moradi-Lakeh M, Nguyen HLT, Nirayo YL, Qorbani M, Ranta A, Roba KT, Safiri S, Santos IS, Satpathy M, Sawhney M, Shiferaw MS, Shiue I, Smith M, Szoeke CEI, Truong NT, Venketasubramanian N, Weldegwergs K, Westerman R, Wijeratne T, Tran BX, Yonemoto N, Feigin VL, Vos T, Murray CJL (2018) Global, regional, and national burden of migraine and tension-type headache, 1990–2016: a systematic analysis for the global burden of disease study 2016. Lancet Neurol 17(11):954–976. https://doi.org/10.1016/S1474-4422(18)30322-3

Lipton RB, Bigal ME, Diamond M, Freitag F, Reed ML, Stewart WF, on behalf of the AMPP Advisory Group (2007) Migraine prevalence, disease burden, and the need for preventive therapy. Neurology 68(5):343–349. https://doi.org/10.1212/01.wnl.0000252808.97649.21

Silberstein SD, Holland S, Freitag F, Dodick DW, Argoff C, Ashman E, Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society (2012) Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: table 1. Neurology 78(17):1337–1345. https://doi.org/10.1212/WNL.0b013e3182535d20

Evers S, Áfra J, Frese A et al (2009) EFNS guideline on the drug treatment of migraine - revised report of an EFNS task force. Eur J Neurol 16(9):968–981. https://doi.org/10.1111/j.1468-1331.2009.02748.x

Silberstein SD, Lipton RB, Dodick DW, Freitag FG, Ramadan N, Mathew N, Brandes JL, Bigal M, Saper J, Ascher S, Jordan DM, Greenberg SJ, Hulihan J, on behalf of the Topiramate Chronic Migraine Study Group (2007) Efficacy and safety of topiramate for the treatment of chronic migraine: a randomized, double-blind, placebo-controlled trial. Headache 47(2):170–180. https://doi.org/10.1111/j.1526-4610.2006.00684.x

Dodick DW, Turkel CC, Degryse RE et al (2010) OnabotulinumtoxinA for treatment of chronic migraine: pooled results from the double-blind, randomized, placebo-controlled phases of the PREEMPT clinical program. Headache 50(6):921–936. https://doi.org/10.1111/j.1526-4610.2010.01678.x

Hepp Z, Dodick DW, Varon SF, Chia J, Matthew N, Gillard P, Hansen RN, Devine EB (2017) Persistence and switching patterns of oral migraine prophylactic medications among patients with chronic migraine: a retrospective claims analysis. Cephalalgia 37(5):470–485. https://doi.org/10.1177/0333102416678382

Edvinsson L, Haanes KA, Warfvinge K, Krause DN (2018) CGRP as the target of new migraine therapies - successful translation from bench to clinic. Nat Rev Neurol 14(6):338–350. https://doi.org/10.1038/s41582-018-0003-1

Tepper S, Ashina M, Reuter U, Brandes JL, Doležil D, Silberstein S, Winner P, Leonardi D, Mikol D, Lenz R (2017) Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol 16(6):425–434. https://doi.org/10.1016/S1474-4422(17)30083-2

10.

Goadsby PJ, Uwe R, Hallstrom Y et al (2017) A controlled trial of erenumab for episodic migraine. N Engl J Med 377(22):2123–2132. https://doi.org/10.1056/NEJMoa1705848

11.

Stauffer VL, Dodick DW, Zhang Q, Carter JN, Ailani J, Conley RR (2018) Evaluation of galcanezumab for the prevention of episodic migraine: the EVOLVE-1 randomized clinical trial. JAMA Neurol 75(9):1080–1088. https://doi.org/10.1001/jamaneurol.2018.1212

12.

Skljarevski V, Matharu M, Millen BA, Ossipov MH, Kim BK, Yang JY (2018) Efficacy and safety of galcanezumab for the prevention of episodic migraine: results of the EVOLVE-2 phase 3 randomized controlled clinical trial. Cephalalgia 38(8):1442–1454. https://doi.org/10.1177/0333102418779543

13.

Detke HC, Goadsby PJ, Wang S, Friedman DI, Selzler KJ, Aurora SK (2018) Galcanezumab in chronic migraine: the randomized, double-blind, placebo-controlled REGAIN study. Neurology 91(24):E2211–E2221. https://doi.org/10.1212/WNL.0000000000006640

14.

Silberstein SD, Dodick DW, Bigal ME, Yeung PP, Goadsby PJ, Blankenbiller T, Grozinski-Wolff M, Yang R, Ma Y, Aycardi E (2017) Fremanezumab for the preventive treatment of chronic migraine. N Engl J Med 377(22):2113–2122. https://doi.org/10.1056/nejmoa1709038

15.

Dodick DW, Silberstein SD, Bigal ME, Yeung PP, Goadsby PJ, Blankenbiller T, Grozinski-Wolff M, Yang R, Ma Y, Aycardi E (2018) Effect of Fremanezumab compared with placebo for prevention of episodic migraine a randomized clinical trial. JAMA 319(19):1999–2008. https://doi.org/10.1001/jama.2018.4853

16.

Lipton RB, Goadsby PJ, Smith J, Schaeffler BA, Biondi DM, Hirman J, Pederson S, Allan B, Cady R (2020) Efficacy and safety of eptinezumab in patients with chronic migraine: PROMISE-2. Neurology 94(13):E1365–E1377. https://doi.org/10.1212/WNL.0000000000009169

17.

Barbanti P, Aurilia C, Egeo G, Fofi L, Cevoli S, Colombo B, Filippi M, Frediani F, Bono F, Grazzi L, Salerno A, Mercuri B, Carnevale A, Altamura C, Vernieri F (2020) Erenumab in the prevention of high-frequency episodic and chronic migraine: Erenumab in real life in Italy (EARLY), the first Italian multicenter, prospective real-life study. Headache. 61(2):363–372. https://doi.org/10.1111/head.14032

18.

Ament M, Day K, Stauffer VL, Skljarevski V, Rettiganti M, Pearlman E, Aurora SK (2021) Effect of galcanezumab on severity and symptoms of migraine in phase 3 trials in patients with episodic or chronic migraine. J Headache Pain 22(1):6. https://doi.org/10.1186/s10194-021-01215-9

19.

Vernieri F, Altamura C, Aurilia C, Brunelli N, Egeo G, Fofi L, Costa CM, Fallacara A, Favoni V, Pierangeli G, Aguggia M, Bertuzzo D, Albanese M, di Fiore P, Frediani F, Cevoli S, Barbanti P (2020) Effectiveness, safety, and tolerability of galcanezumab in a real-life setting in patients with migraine in Italy (the GARLIT study). Neurol Sci 41(S2):487–488. https://doi.org/10.1007/s10072-020-04669-y

20.

Headache Classification Committee of the International Headache Society (IHS) (2018) The International Classification of Headache Disorders, 3rd edition. Cephalalgia 38:1–211. https://doi.org/10.1177/0333102417738202

21.

Sacco S, Bendtsen L, Ashina M, Reuter U, Terwindt G, Mitsikostas DD, Martelletti P (2019) European headache federation guideline on the use of monoclonal antibodies acting on the calcitonin gene related peptide or its receptor for migraine prevention. J Headache Pain 20(1):6. https://doi.org/10.1186/s10194-018-0955-y

22.

(2019) The American Headache Society Position Statement On Integrating New Migraine Treatments Into Clinical Practice. Headache 59:1–18. https://doi.org/10.1111/head.13456

23.

Barbanti P, Aurilia C, Dall’Armi V, Egeo G, Fofi L, Bonassi S (2016) The phenotype of migraine with unilateral cranial autonomic symptoms documents increased peripheral and central trigeminal sensitization. A case series of 757 patients. Cephalalgia 36(14):1334–1340. https://doi.org/10.1177/0333102416630579

24.

Houts CR, Wirth RJ, McGinley JS et al (2020) Content validity of HIT-6 as a measure of headache impact in people with migraine: a narrative review. Headache 60(1):28–39. https://doi.org/10.1111/head.13701

25.

D’Amico D, Mosconi P, Genco S et al (2001) The migraine disability assessment (MIDAS) questionnaire: translation and reliability of the Italian version. Cephalalgia 21(10):947–952. https://doi.org/10.1046/j.0333-1024.2001.00277.x

26.

Schwedt TJ, Kuruppu DK, Dong Y, Standley K, Yunes-Medina L, Pearlman E (2021) Early onset of effect following galcanezumab treatment in patients with previous preventive medication failures. J Headache Pain 22(1):15. https://doi.org/10.1186/s10194-021-01230-w

27.

Mulleners WM, Kim BK, Láinez MJA, Lanteri-Minet M, Pozo-Rosich P, Wang S, Tockhorn-Heidenreich A, Aurora SK, Nichols RM, Yunes-Medina L, Detke HC (2020) Safety and efficacy of galcanezumab in patients for whom previous migraine preventive medication from two to four categories had failed (CONQUER): a multicentre, randomised, double-blind, placebo-controlled, phase 3b trial. Lancet Neurol 19(10):814–825. https://doi.org/10.1016/S1474-4422(20)30279-9

28.

Detke U, Reuter U, Lucas C, et al (2020) Galcanezumab in patients with treatment-resistant migraine: results from the open-label phase of the CONQUER phase 3 trial. Poster prensentation 14th Eur Headache Fed (EHF); Virtual 2020; June 29 – July 2, 2020

29.

Förderreuther S, Zhang Q, Stauffer VL et al (2018) Preventive effects of galcanezumab in adult patients with episodic or chronic migraine are persistent: data from the phase 3, randomized, double-blind, placebo-controlled EVOLVE-1, EVOLVE-2, and REGAIN studies. J Headache Pain 19. https://doi.org/10.1186/s10194-018-0951-2

30.

Ornello R, Ripa P, Pistoia F, Degan D, Tiseo C, Carolei A, Sacco S (2015) Migraine and body mass index categories: a systematic review and meta-analysis of observational studies. J Headache Pain 16(1):27. https://doi.org/10.1186/s10194-015-0510-z

31.

Recober A, Goadsby PJ (2010) Calcitonin gene-related peptide: a molecular link between obesity and migraine? Drug News Perspect 23(2):112–117. https://doi.org/10.1358/dnp.2010.23.2.1475909

32.

Schiller Y, Najjar Y (2008) Quantifying the response to antiepileptic drugs: effect of past treatment history. Neurology 70(1):54–65. https://doi.org/10.1212/01.wnl.0000286959.22040.6e

33.

Franco V, Perucca E (2015) The pharmacogenomics of epilepsy. Expert Rev Neurother 15(10):1161–1170. https://doi.org/10.1586/14737175.2015.1083424

34.

D’Antona L, Matharu M (2019) Identifying and managing refractory migraine: barriers and opportunities? J Headache Pain 20(1):89. https://doi.org/10.1186/s10194-019-1040-x

35.

Altamura C, Viticchi G, Fallacara A, Costa CM, Brunelli N, Fiori C, Silvestrini M, Vernieri F (2021) Erenumab does not alter cerebral hemodynamics and endothelial function in migraine without aura. Cephalalgia 41(1):90–98. https://doi.org/10.1177/0333102420956692

36.

Concato J, Shah N, Horwitz RI (2000) Randomized, controlled trials, observational studies, and the hierarchy of research designs. N Engl J Med 342(25):1887–1892. https://doi.org/10.1056/nejm200006223422507

37.

Benson K, Hartz AJ (2000) A comparison of observational studies and randomized, controlled trials. N Engl J Med 342(25):1878–1886. https://doi.org/10.1056/nejm200006223422506

38.

Autret A, Valade D, Debiais S (2012) Placebo and other psychological interactions in headache treatment. J. Headache Pain 13(3):191–198. https://doi.org/10.1007/s10194-012-0422-0

Title: Galcanezumab for the prevention of high frequency episodic and chronic migraine in real life in Italy: a multicenter prospective cohort study (the GARLIT study)
Authors: Fabrizio Vernieri
Claudia Altamura
Nicoletta Brunelli
Carmelina Maria Costa
Cinzia Aurilia
Gabriella Egeo
Luisa Fofi
Valentina Favoni
Giulia Pierangeli
Carlo Lovati
Marco Aguggia
Florindo d’Onofrio
Alberto Doretti
Paola Di Fiore
Cinzia Finocchi
Renata Rao
Francesco Bono
Angelo Ranieri
Maria Albanese
Sabina Cevoli
Piero Barbanti
for the GARLIT Study Group
Publication date: 01-12-2021
Publisher: Springer Milan
Keywords: Migraine
Headache
Galcanezumab
Published in: The Journal of Headache and Pain / Issue 1/2021
Print ISSN: 1129-2369
Electronic ISSN: 1129-2377
DOI: https://doi.org/10.1186/s10194-021-01247-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Galcanezumab for the prevention of high frequency episodic and chronic migraine in real life in Italy: a multicenter prospective cohort study (the GARLIT study)

Abstract

Background

Methods

Results

Conclusions

Trial registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Trial registration

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