Efficacy of Anti-IL-6 Treatments on Migraine in Patients Treated With Anti-IL-6 for a Rheumatological Condition (RHUMIL-6)

Migraine affects approximately 15% of the global population. Its prevalence doubles or even triples in individuals with chronic inflammatory conditions, such as chronic inflammatory rheumatic diseases (34%), multiple sclerosis (MS) (46%), or endometriosis (35%). The prevalence of chronic migraine - defined as at least 15 headache days per month (on average over the past 3 months), of which at least 8 days have migrainous features - is also higher in certain conditions such as MS (4%) compared to the general population (1%). The mechanisms underlying migraine and its chronification remain uncertain, but inflammation appears to play an important role in its pathophysiology: it is present from the onset of a migraine attack, represented by the release of pro-inflammatory cytokines that sensitize the trigeminal system and promote the occurrence of new attacks. The investigators' recent bibliographic work has demonstrated elevated levels of interleukin-6 (IL-6), a pro-inflammatory cytokine, in the blood of episodic migraine patients between attacks (migrainous status) compared to non-migrainous subjects, and in chronic migraine patients compared to episodic migraine patients (chronic migraine status). IL-6 appears to play a role in the pathophysiology of migraine, and elevated levels may represent a marker of poorer response to prophylactic treatments. IL-6 levels are also elevated in inflammatory rheumatic diseases and are associated with disease severity. The efficacy of IL-6 pathway-blocking treatments in inflammatory rheumatic diseases is now well established, and these agents are commonly used for this indication. IL-6 could therefore represent a shared pathophysiological link between migraine and inflammatory rheumatic diseases. However, no study to date has measured the effect of IL-6-blocking treatments on migraine. This study therefore aims to assess the effect of anti-IL-6 treatments on migraine in migrainous patients followed in the rheumatology department of the Clermont-Ferrand University Hospital and treated with anti-IL-6 therapy for their rheumatological condition (rheumatoid arthritis, polymyalgia rheumatica, etc.). It will provide preliminary results regarding the effect of anti-IL-6 agents on migraine and could justify future therapeutic studies.

Study Overview

• Status: Not yet recruiting
• Conditions: Migraine
• Intervention / Treatment: Other: Migraine assessement; Other: Patient Global Impression of Change

Detailed Description

In this study, the investigators aim to measure the proportion of patients experiencing a reduction in migraine among those treated with anti-IL-6 therapy for their rheumatological condition, in terms of migraine frequency or intensity (primary objective). The secondary objectives are to :

• Measure the proportion of patients experiencing a reduction in migraine among those treated with anti-IL-6 therapy for their rheumatological condition, in terms of (a) frequency, (b) intensity, (c) both frequency and intensity of migraines.
• Compare the proportion of patients experiencing a reduction in migraine in terms of frequency or intensity between those treated with anti-IL-6 and a group of patients treated with anti-TNF (tumor necrosis factor) therapy.

From a pre-established list compiled by the investigators of patients on anti-IL-6 therapy (anti-IL-6 group) and patients on anti-TNF therapy (control group), all patients will be contacted by phone to identify those with migraine, using the International Classification of Headache Disorders, version 3 (ICHD-3) criteria from the International Headache Society (IHS). In cases where migraine is present, the effect of anti-IL-6 (anti-IL-6 group) or anti-TNF (control group) treatment in terms of the proportion of patients experiencing a reduction in migraine will be assessed using the Patient Global Impression of Change (PGI-C) score: a validated tool, widely used, translated into French and made available by eProvide - Mapi Research Trust [https://eprovide.mapi-trust.org/instruments/patient-global-impressions-scale-change-improvement-severity#need_this_questionnaire]) (comparison: before vs. during treatment). The episodic or chronic nature of migraine will be determined during the telephone interview according to the following criteria: fewer than 15 monthly headache days for episodic migraine, and at least 15 monthly headache days - of which at least 8 days have migrainous features - for chronic migraine (IHS definition). All patients on this list who meet the inclusion and non-inclusion criteria and agree to participate in the study will be enrolled. The inclusion of a control group - comprising patients treated with a biotherapy other than anti-IL-6, namely anti-TNF agents - will strengthen the level of attribution of the measured effect to anti-IL-6 treatment and help offset recall bias.

• Study Type: Observational
• Enrollment (Estimated): 320

Contacts and Locations

• Study Contact: Name: Lise Laclautre; Phone Number: 0473754963; Email: promo_interne_drci@chu-clermontferrand.fr

Study Locations

• France
  • Clermont-Ferrand, France
    • Chu Clermont-Ferrand
    • Principal Investigator: Sylvain MATHIEU
    • Contact: Lise Laclautre; Phone Number: 0473754963; Email: promo_interne_drci@chu-clermontferrand.fr
    • Sub-Investigator: Emily STUCHFIELD-DENBY

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Migrainous patients, identified using the International Classification of Headache Disorders, version 3 (ICHD-3) criteria from the International Headache Society (IHS) during the telephone call, will complete the Patient Global Impression of Change (PGI-C) score to determine whether the treatment (anti-IL-6 or anti-TNF) is associated with a reduction in migraines or not.

Description

Inclusion Criteria (for screening) :

• at least 18 years old
• ongoing or previous anti-IL-6 (anti-IL-6 group) or anti-TNF (anti-TNF group) therapy, taken for at least 3 months

Inclusion Criteria (patients to be enrolled) : migrainous patients, identified using the International Classification of Headache Disorders, version 3 (ICHD-3) criteria from the International Headache Society (IHS) during the telephone call

Exclusion Criteria:

• Biotherapy treatment in the context of a diagnosis of giant cell arteritis
• Verbal communication not possible
• No affiliation to the French national health insurance system, legal protection measure (guardianship, curatorship, judicial protection)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Anti-IL-6 group; Patient on anti-IL-6 therapy	Other: Migraine assessement; Migraine frequency and intensity will be assessed in patients on anti-IL-6 (anti-IL-6 group) and anti-TNF (anti-TNF group).; Other: Patient Global Impression of Change; Migraine frequency and intensity will be assessed in patients taking anti-IL-6 (anti-IL-6 group) and anti-TNF therapy (anti-TNF group) using the Patient Global Impression of Change (PGI-C) score.
Anti-TNF group; Patients on anti-TNF therapy	Other: Migraine assessement; Migraine frequency and intensity will be assessed in patients on anti-IL-6 (anti-IL-6 group) and anti-TNF (anti-TNF group).; Other: Patient Global Impression of Change; Migraine frequency and intensity will be assessed in patients taking anti-IL-6 (anti-IL-6 group) and anti-TNF therapy (anti-TNF group) using the Patient Global Impression of Change (PGI-C) score.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Global Impression of Change (PGI-C) on migraine (frequency or intensity)	Measure change in migraine under anti-IL-6, in terms of frequency or intensity, according to the PGI-C score.	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Global Impression of Change on migraine (frequency)	Measure change in migraine under anti-IL-6, in terms of migraine frequency, according to the PGI-C score.	Day 1
Patient Global Impression of Change on migraine (intensity)	Measure change in migraine under anti-IL-6, in terms of migraine intensity, according to the PGI-C score.	Day 1
Patient Global Impression of Change on migraine (frequency and intensity)	Measure change in migraine under anti-IL-6, in terms of both frequency and intensity, according to the PGI-C scores.	Day 1

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand

Study record dates

Study Major Dates

• Study Start (Estimated): May 26, 2026
• Primary Completion (Estimated): May 26, 2027
• Study Completion (Estimated): May 26, 2027

Study Registration Dates

• First Submitted: May 13, 2026
• First Submitted That Met QC Criteria: May 13, 2026
• First Posted (Actual): May 20, 2026

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Inflammation; Migraine; Chronic inflammatory rheumatic diseases; Anti-IL-6 therapy
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Headache Disorders, Primary; Headache Disorders; Pathological Conditions, Signs and Symptoms; Migraine Disorders; Inflammation
• Other Study ID Numbers: RNI 2025 MATHIEU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No