What to do if a patient on a CGRP (Calcitonin Gene-Related Peptide) biologic agent experiences a worsening headache?

Management of Worsening Headache on CGRP Biologic Agent

If a patient on a CGRP biologic agent (monoclonal antibody for prevention) experiences a worsening headache, treat the acute breakthrough migraine with combination therapy of a triptan plus an NSAID or acetaminophen as first-line acute treatment. 1

Acute Treatment Strategy for Breakthrough Migraines

First-Line Acute Treatment

• Use combination therapy with a triptan and an NSAID or acetaminophen to treat the acute breakthrough headache, as this provides superior efficacy compared to monotherapy 1
• Counsel the patient to begin acute treatment as soon as possible after headache onset to improve efficacy 1

Alternative Acute Treatment Options (If First-Line Fails)

• Consider CGRP antagonists-gepants (rimegepant, ubrogepant, or zavegepant) if the patient does not tolerate or has inadequate response to triptan plus NSAID/acetaminophen combination 1
• Consider lasmiditan (ditan) if all other pharmacologic treatments fail 1
• Use nonoral triptan with antiemetic if severe nausea or vomiting is present 1

Critical Medication Overuse Headache Warning

• Monitor for medication overuse headache, defined as headache occurring ≥15 days per month for at least 3 months due to overuse of acute medication 1
• The threshold varies by medication: ≥15 days/month for NSAIDs, ≥10 days/month for triptans and CGRP antagonists 1, 2
• Avoid opioids and butalbital completely for acute migraine treatment 1

Reassessing the Preventive CGRP Biologic

Timing of Efficacy Assessment

• Assess efficacy of CGRP monoclonal antibodies only after 3-6 months of treatment, as immediate efficacy is rarely observed 1, 2
• Do not abandon preventive treatment prematurely during these early stages 1

When to Consider Treatment Adjustment

• If episodic migraine occurs frequently or acute treatment does not provide adequate response, reassess the preventive regimen 1
• Consider whether the patient is experiencing true treatment failure versus inadequate acute medication management 1
• Consider pausing preventive therapy after 6-12 months of successful treatment to determine if it can be stopped 1, 2

Combination Preventive Therapy Consideration

• Consider combining the CGRP monoclonal antibody with onabotulinumtoxinA for resistant chronic migraine cases, though evidence is limited 3
• This combination may bring benefits for patients not responding adequately to monotherapy 3

Lifestyle and Trigger Management

Before adjusting medications, ensure the following are optimized 1:

• Adequate hydration and regular meals 1
• Sufficient and consistent sleep (7-9 hours) 1
• Regular moderate to intense aerobic exercise 1
• Stress management with relaxation techniques or mindfulness practices 1
• Weight loss if overweight or obese (obesity is a negative predictor of CGRP response) 3
• Identify and modify specific migraine triggers through detailed history 1

Common Pitfalls to Avoid

• Do not prematurely discontinue the CGRP biologic before the 3-6 month assessment period 1, 2
• Do not use the preventive CGRP biologic (monoclonal antibody) to treat acute breakthrough headaches - these are for prevention only 1
• Do not allow patients to overuse acute medications, which can lead to medication overuse headache and worsen the overall migraine pattern 1
• Do not assume treatment failure if lifestyle factors and acute medication optimization have not been addressed 1