In search of a gold standard patient-reported outcome measure to use in the evaluation and treatment-decision making in migraine prevention. A real-world evidence study

Abstract

Background: Patient-Reported Outcomes (PROs) have been developed to numerically quantify disability, impact and quality of life. They have been widely used in migraine clinical trials. However, we still do not know which PRO more accurately reflects preventive treatment response from a patient's perspective or which one may help us with treatment decisions in clinical practice. They have been used to enforce the efficacy results in clinical trials and real-world evidence so far. The aim of this study was to analyze which PROM is (1) better correlated with all primary efficacy endpoints and (2) which one is better associated with treatment continuation with CGRP-mAbs at week-12, which is usually the moment when this decision is made.

Methods: Patients with migraine who had received 3 administrations of CGRP-mAbs were evaluated in this prospective cohort study. Primary efficacy outcomes considered: a change in migraine days (MMD), headache days (MHD), pain intensity (INT), acute medication days (AMD) and 50% responder rate. The Spearman coefficient (rs) was the measure used for quantify the strength of the correlation between PROMs and treatment efficacy outcomes changes. A stepwise logistic regression identified which PROM was independently associated with treatment continuation at week-12.

Results: 263 patients completed 12 weeks of treatment. The efficacy outcomes and PROMs scores were statistically significantly reduced at week-12 for all patients. The role function-restrictive (RFR) domain of the Migraine-Specific Quality of Life (MSQ) questionnaire was statistically significantly correlated with all primary efficacy outcomes. Relative changes in MSQ total score (OR[95%]: 0.840[0.619-0.973]; p=0.037) and Patient Global Impression of Change (PGIC) scale (OR[95%]: 15.569[6.254-31.533]; p<0.001) were the PROMs associated with treatment continuation as independent factors at week-12.

Conclusions: Changes in MSQ questionnaire and PGIC scale at week-12 were the PROMs with higher association with CGRP-mAbs response from a patient's perspective and medical decision-taking.

Keywords: Efficacy; Headache; Health-related quality of life; Migraine; Outcomes; Patient-reported outcome; anti-CGRP monoclonal antibodies.

Conflict of interest statement

In relation with this paper the authors have nothing to disclose. AA has received honoraria as speaker from Allergan-AbbVie and education from Novartis and Eli Lilly. VJG has nothing to disclose. EC has received honoraria as speaker from Novartis. MT-F has received honoraria as a speaker from Allergan-AbbVie, Chiesi, Eli Lilly and Novartis. In the last 18 months, PP-R has received honoraria as a consultant and speaker from Allergan-AbbVie, Biohaven, Chiesi, Eli Lilly, Medscape, Neurodiem, Novartis and Teva Pharmaceuticals. Her research group has received research grants from Allergan-AbbVie, AGAUR, la Caixa foundation, Migraine Research Foundation, FEDER RISC3CAT, Instituto Investigación Carlos III, MICINN, PERIS; and has received funding for clinical trials from Alder, Allergan-AbbVie, Electrocore, Eli Lilly, Novartis and Teva. She is a trustee member of the board of the International Headache Society and a member of the Council of the European Headache Federation. She is in the editorial board of Revista de Neurologia. She is an associate editor for Cephalalgia, Headache, Frontiers of Neurology and an advisory Scientific member of the Editorial Board of The Journal of Headache and Pain. She is a member of the Clinical Trials Guidelines Committee and Scientific Committee of the International Headache Society. She has edited the Guidelines for the Diagnosis and Treatment of Headache of the Spanish Neurological Society. She is the founder of www.midolordecabeza.org. PP-R does not own stocks from any pharmaceutical company.

© 2021. The Author(s).

Figures

Fig. 1

Relative changes (∆%) correlations between treatment efficacy outcomes improvement and PROMs changes (A: MIDAS, HIT-6, MSQT, BAI, BDI-II, MIG-SCOG; B: MSQT, MSQRFR, MSQRFP, MSQEF). Pie charts represent the strength of the correlation (rs) between pairwise ∆ and color the direction of this relationship (blue: positive, red: negative). Blank cells refer to non-statistically significantly correlation between pairwise ∆. Abbreviations MHD: monthly headache days; MMD: monthly migraine days; INT: headache pain intensity; AMD: days of acute medication intake; AMP: acute medication burden (pills/month); MIDAS: migraine disability assessment; HIT-6: headache impact test; MSQT: migraine-specific quality of life questionnaire (total score); MSQ-RFR: MSQ role-function restrictive; MSQ-RFP: MSQ role-function preventive; MSQ-EF: MSQ emotional function; BAI: Beck anxiety inventory; BDI-II: Beck depression inventory-second edition; MIG-SCOG: migraine attacks-subjective cognitive impairment scale.

Fig. 2

Odds Ratio (95% CI) estimated from the logistic regression analysis of the significant clinical predictors associated to CGRP-mAb treatment continuation (A) and statistical significance of the MSQT cut-off and treatment response (B). (A) Odds ratio (95% CI) estimated from the 10-fold CV of the stepwise logistic regression with selection criteria of minimizing the AIC for a variable to be eliminated from the selected model. (B) ***P-value < 0.0001; significance assessed with Fisher’s exact test. MSQ cut-off selection from ROC using Youden’s index. Abbreviations: PGI-C: patient global impression scale; MSQT: migraine-specific quality of life questionnaire (total score); MHD: monthly headache days; MMD: monthly migraine days; RR.