TY - JOUR
T1 - Benefits Beyond Headache Days With OnabotulinumtoxinA Treatment
T2 - A Pooled PREEMPT Analysis
AU - Diener, Hans Christoph
AU - Dodick, David W.
AU - Lipton, Richard B.
AU - Manack Adams, Aubrey
AU - DeGryse, Ronald E.
AU - Silberstein, Stephen D.
N1 - Funding Information:
Sponsorship for this study and Rapid Service Fee were funded by Allergan (prior to its acquisition by AbbVie). All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. Writing and editorial assistance was provided to the authors by Sean Sheffler-Collins, PhD, at Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, USA, and was funded by AbbVie. The opinions expressed in this article are those of the authors. The authors received no honorarium/fee or other form of financial support related to the development of this article. Some of the data included in this manuscript were previously presented in poster form at the 19th Congress of the International Headache Society (IHC 2019) September 5–8, 2019, Dublin, Ireland; and the 13th Annual Headache Cooperative of the Pacific (HCOP) Winter Conference January 24–25, 2020, Ojai, CA, USA. Hans-Christoph Diener, MD, PhD: Received honoraria for participation in clinical trials, contribution to advisory boards or oral presentations in the last 3 years from: Alder, AbbVie, Amgen, Bristol-Myers Squibb, Electrocore, Ipsen Pharma, Eli Lilly, Medtronic, MSD, Novartis, Pfizer, Teva, and Weber & Weber. Financial support for research projects was provided by AbbVie. HCD serves on the editorial boards of Cephalalgia and Lancet Neurology. HCD co-chairs the Clinical Guidelines Committee of the German Society of Neurology and is member of the Clinical Trials Committee of the International Headache Society. David W. Dodick, MD: Reports the following conflicts within the past 12 months: Consulting: AEON, Amgen, Clexio, Cerecin, AbbVie, Alder, Biohaven, Linpharma, Lundbeck, Promius, Eli Lilly, eNeura, Novartis, Impel, Theranica, WL Gore, Nocira, XoC, Zosano, Upjohn (Division of Pfizer), Pieris, Revance, Equinox. Honoraria: CME Outfitters, Curry Rockefeller Group, DeepBench, Global Access Meetings, KLJ Associates, Majallin LLC, Medlogix Communications, Miller Medical Communications, Southern Headache Society (MAHEC), WebMD Health/Medscape, Wolters Kluwer, Oxford University Press, Cambridge University Press. Research Support: Department of Defense, National Institutes of Health, Henry Jackson Foundation, Sperling Foundation, American Migraine Foundation, Patient Centered Outcomes Research Institute (PCORI). Stock Options/Shareholder/Patents/Board of Directors: Aural Analytics (options), ExSano (options), Palion (options), Healint (options), Theranica (options), Second Opinion/Mobile Health (options), Epien (options/board), Nocira (options), Ontologics (options/board), King-Devick Technologies (options/board), Precon Health (options/board). Patent 17189376.1-1466:vTitle: Botulinum Toxin Dosage Regimen for Chronic Migraine Prophylaxis. Richard B. Lipton, MD: Serves as consultant or advisory board member or has received honoraria from American Academy of Neurology, Alder, AbbVie, American Headache Society, Amgen, Biohaven, Biovision, Boston Scientific, Dr. Reddy’s, Electrocore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Merck, Pernix, Pfizer, Teva, Trigemina, Vector, and Vedanta. Holds stock options in eNeura and Biohaven. Aubrey Manack Adams, PhD and Ronald E. DeGryse, MS, MA: Full-time employees of AbbVie and may hold stock in AbbVie. Stephen D. Silberstein, MD: Consultant and/or advisory panel member for and has received honoraria from Alder Biopharmaceuticals, AbbVie, Amgen, Avanir, eNeura, ElectroCore Medical, Labrys Biologics, Medscape, Medtronic, Neuralieve, NINDS, Pfizer, and Teva. His employer receives research support from AbbVie, Amgen, Cumberland Pharmaceuticals, ElectroCore Medical, Labrys Biologics, Eli Lilly, Mars, and Troy Healthcare. Both trials discussed in this article were conducted in accordance with the Declaration of Helsinki Code of Federal Regulations and Good Clinical Practices and US requirements of public registration (NCT00156910 [PREEMPT 1] and NCT00168428 [PREEMPT 2]). Investigators obtained approval from the independent ethics committee or local institutional review board at each investigational site prior to study initiation. Written informed consent was obtained from each randomized patient. Data reported in this manuscript are available within the article and/or its supplementary materials. AbbVie will share de-identified patient-level data and/or study-level data, including protocols and clinical study reports, for phase 2–4 trials completed after 2008 that are registered on ClinicalTrials.gov or EudraCT. The indication studied in the trial must have regulatory approval in the United States and/or the European Union and the primary manuscript from the trial must be published prior to data sharing. To request access to the data, the researcher must sign a data use agreement. All shared data are to be used for non-commercial purposes only. More information can be found on https://www.allerganclinicaltrials.com/PatientDataRequest.htm.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Introduction: The double-blind, phase 3 PREEMPT trials demonstrated the efficacy and tolerability of onabotulinumtoxinA for headache prevention in adults with chronic migraine. This post hoc analysis evaluated the effect of onabotulinumtoxinA on clinically meaningful changes in headache severity, headache-related impact, and quality of life. Methods: Pooled, 24-week data were used to determine percentages of patients meeting responder criteria for the change in headache days (≥ 50% reduction in headache-day frequency), Headache Impact Test (HIT-6; ≥ 5-point improvement), MSQ Role Function-Restrictive (MSQ-RFR; ≥ 10.9-point improvement), and Average Daily Headache Severity (ADHS; ≥ 1-point improvement on a 4-point ordinal scale [0 = no pain, 3 = severe pain]). Results: In the pooled analysis population (N = 1384; onabotulinumtoxinA, n = 688; placebo, n = 696), significantly more patients treated with onabotulinumtoxinA compared with placebo were responders on HIT-6 (40.8 vs. 25.3%), MSQ-RFR (59.0 vs. 40.2%), and ADHS (35.5 vs. 22.4%) measures, and achieved traditional ≥ 50% reduction in headache days (44.8 vs. 34.2%; all P < 0.001). At least one responder criterion was met by 72.1% and 56.6% of onabotulinumtoxinA- and placebo-treated patients, respectively; all four were met by 20.4% and 8.6%, respectively (P < 0.001). Linear regression analysis showed that approximately 20% of the variance in HIT-6 and MSQ-RFR improvement was explained by improvement in headache days. Conclusions: Treatment with onabotulinumtoxinA for 24 weeks was associated with clinically meaningful benefits beyond reduction in headache days; including reductions in headache severity and headache-related impact, and improved quality of life. While 45% of patients met responder criteria for monthly headache days, over 70% had clinically meaningful improvements on at least one outcome measure. Trial Registration: ClinicalTrials.gov identifier, NCT00156910 (PREEMPT 1) and NCT00168428 (PREEMPT 2).
AB - Introduction: The double-blind, phase 3 PREEMPT trials demonstrated the efficacy and tolerability of onabotulinumtoxinA for headache prevention in adults with chronic migraine. This post hoc analysis evaluated the effect of onabotulinumtoxinA on clinically meaningful changes in headache severity, headache-related impact, and quality of life. Methods: Pooled, 24-week data were used to determine percentages of patients meeting responder criteria for the change in headache days (≥ 50% reduction in headache-day frequency), Headache Impact Test (HIT-6; ≥ 5-point improvement), MSQ Role Function-Restrictive (MSQ-RFR; ≥ 10.9-point improvement), and Average Daily Headache Severity (ADHS; ≥ 1-point improvement on a 4-point ordinal scale [0 = no pain, 3 = severe pain]). Results: In the pooled analysis population (N = 1384; onabotulinumtoxinA, n = 688; placebo, n = 696), significantly more patients treated with onabotulinumtoxinA compared with placebo were responders on HIT-6 (40.8 vs. 25.3%), MSQ-RFR (59.0 vs. 40.2%), and ADHS (35.5 vs. 22.4%) measures, and achieved traditional ≥ 50% reduction in headache days (44.8 vs. 34.2%; all P < 0.001). At least one responder criterion was met by 72.1% and 56.6% of onabotulinumtoxinA- and placebo-treated patients, respectively; all four were met by 20.4% and 8.6%, respectively (P < 0.001). Linear regression analysis showed that approximately 20% of the variance in HIT-6 and MSQ-RFR improvement was explained by improvement in headache days. Conclusions: Treatment with onabotulinumtoxinA for 24 weeks was associated with clinically meaningful benefits beyond reduction in headache days; including reductions in headache severity and headache-related impact, and improved quality of life. While 45% of patients met responder criteria for monthly headache days, over 70% had clinically meaningful improvements on at least one outcome measure. Trial Registration: ClinicalTrials.gov identifier, NCT00156910 (PREEMPT 1) and NCT00168428 (PREEMPT 2).
KW - Botulinum toxin type A
KW - Chronic migraine
KW - Quality of life
KW - Responder rate
UR - http://www.scopus.com/inward/record.url?scp=85097730869&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85097730869&partnerID=8YFLogxK
U2 - 10.1007/s40122-020-00198-w
DO - 10.1007/s40122-020-00198-w
M3 - Article
AN - SCOPUS:85097730869
SN - 2193-8237
VL - 9
SP - 683
EP - 694
JO - Pain and Therapy
JF - Pain and Therapy
IS - 2
ER -