People with migraine have more options for prevention than ever before. New migraine treatments for long-term prevention are expanding treatment choices, with CGRP-targeted therapies among the biggest advances. These medications act on CGRP, which is the abbreviation of calcitonin gene-related peptide and plays a role in transmitting signals of pain in migraines.
There have been studies conducted recently about treatments after the initial few months of medication. In a study done in the year 2026, it was found that in some cases, research suggests that the preventive benefits of anti-CGRP therapies may be sustained in some patients for two years or longer.
These findings are promising. However, it is important to know that most of the information related to the efficacy of long-term treatment comes from observational studies.
Key Takeaways
- CGRP plays an important role in migraine pain signaling and sensitization.
- CGRP-targeted therapies either inhibit CGRP or its receptor.
- Gepants are small molecule drugs which are targeted towards the CGRP pathway.
- There are four CGRP monoclonal antibodies which have been FDA approved in America for migraine prophylaxis.
- Real-world evidence suggests that some patients benefit from this therapy for up to two years.
- There are cases when certain patients will only show positive results after a while, and therefore personalized assessments are necessary.
- CGRP-targeted therapies may benefit some individuals who suffer from chronic migraines and medication-overuse headaches.
- Botox continues to be used successfully in chronic migraines.
- So far, the safety profile is positive, but ongoing surveillance is needed.
- The future of migraine treatment may well be personalized.
How Does Migraine Develop?
Migraine is a neurological condition that occurs in connection with the trigeminovascular system, which is vital in pain transmission. During an attack, trigeminal nerves are capable of releasing CGRP. This substance may cause pain transmission to be intensified and cause sensitization in migraine.
CGRP subsequently binds to the receptor, facilitating the amplification of pain transmission.
Simply explained:
Trigeminal activation → CGRP secretion → receptor activation → intensified pain transmission → migraine manifestations
The pathway has led to the identification of CGRP as an effective therapeutic target.
How Do CGRP Treatments Work?
CGRP-targeted medicines work by blocking different parts of this pain pathway.
Monoclonal Antibodies
Some monoclonal antibodies bind directly to CGRP, while erenumab blocks the CGRP receptor. CGRP-targeting antibodies include:
- Fremanezumab
- Galcanezumab
- Eptinezumab
- Gepants
Gepants are small-molecule medicines that block the CGRP receptor.
Examples include:
- Atogepant
- Rimegepant
- Ubrogepant
- Zavegepant
Based on the drug, pageants can be prescribed for either preventive purposes, acute treatment, or both.
CGRP Monoclonal Antibodies Approved by the FDA
There are four monoclonal antibodies targeting the CGRP pathway that have received approval in the U.S. for the prevention of migraines:
- Erenumab — Acts on the CGRP receptor and is administered through subcutaneous injection.
- Fremanezumab — Acts on CGRP and administered via subcutaneous injection.
- Galcanezumab — Acts on CGRP and administered via subcutaneous injection.
- Eptinezumab — Acts on CGRP and administered via intravenous infusion.
What Does Recent Research Show?
Long-term research is becoming more and more important, because treatment of migraines requires several years.
Recent findings include:
- 24-month study: A 2026 real-world study conducted on 307 subjects demonstrated a significant decrease in the number of migraine days per month. The response rate was >50%, increasing from 45.9% at 3 months to 71.0% at 24 months. Adverse events were noted in 12.6% of subjects and were generally mild.
- EUREkA 2-Year Cohort Study: In a 2026 prospective observational study, 1,340 patients who reached 24 months were analyzed. At 24 months, 60.4% achieved at least a 50% reduction in monthly headache days. Among patients with sufficient longitudinal data, 53.8% met the study’s definition of sustained response.
- 36 month study: A distinct study in Japan in 2026 involving 50 patients had follow-ups over a period of up to three years. The 28 who were still on treatment at the end of the third year experienced a reduction in the number of monthly migraines from 12.0 to 5.6.
These results collectively indicate that there is potential for some patients to gain from CGRP therapy beyond one year. However, since the investigations have been observational, factors such as choice of therapy, condition and follow-up could have impacted the outcome.
Some Patients May Respond Later
The response to treatment for migraine is not uniform across all people. According to a 2026 study involving 307 participants, there were individuals who only got their response after the early testing time frame. Such people had a greater burden of migraine and a history of failure in preventive therapy.
Doctors may consider:
- Response over time
- Previous treatment failures
- Side effects
- Individual treatment goals
Failure to show immediate results does not indicate that an ineffective therapy must continue forever. Treatments should be individualized.
Chronic Migraine and Medication—Overuse Headache
CGRP-related interventions could also prove useful for chronic migraines and MOH.
According to a 2026 meta-analysis of 7 randomized studies with 3,094 participants, anti-CGRP monoclonal antibodies decreased the number of migraine days and acute medication intake. In addition, they increased the possibility of a 50% reduction of migraine days and increased the likelihood of medication-overuse resolution.
The incidence of adverse events was not significantly increased.
Key findings:
- Fewer monthly migraine days
- Less use of acute headache medicines
- More patients achieving ≥50% improvement
- Higher rates of medication-overuse resolution
- No significant increase in adverse events
- More long-term research is still needed.
Botox Still Has a Role
- Although medications utilizing CGRP have expanded the range of preventive treatments for migraines, they have not replaced the current treatment methods.
- One such example is onabotulinumtoxinA (Botox), which is approved to treat chronic migraines. However, its mode of action differs from that of CGRP-based treatments.
- Furthermore, scientists are exploring how a combination treatment based on varied modes of actions can work for some individuals. Initial results seem promising.
How Safe Are CGRP Treatments?
CGRP therapies have had good safety and tolerability profiles, with severe adverse effects not being reported frequently. However, long-term monitoring is still essential since CGRP is involved in processes such as blood vessel regulation.
Recent findings:
- 24-month study: Adverse events were generally mild.
- Three-year real-world cohort: Among 50 patients followed in Japan, 28 continued anti-CGRP therapy for three years. No treatment discontinuations were linked to adverse effects.
- Long-term data: The findings are positive, but the consequences of long-term CGRP inhibition still require investigation.
The selection of therapy will depend on the drug, patient’s past history, concomitant therapies, possible adverse reactions, and individual preference.
Why Doesn’t the Same Treatment Work for Everyone?
Among the major difficulties of migraine management is the problem of choosing the optimal treatment option for individual patients. Researchers are studying whether factors such as:
- Migraine characteristics
- Previous treatment response
- Genetics
- Other biological differences
- Coexisting conditions
- Can help predict treatment success.
Better prediction will ultimately be able to decrease the amount of trial and error involved when initiating preventative treatment.
The Future of New Migraine Treatments for Long-Term Prevention
The future of migraine treatment may well be more personalized migraine management, aiding physicians in determining which treatment is right for their patient. Key research areas include:
- Treatment-response biomarkers
- Genetic and biological factors
- Optimal treatment duration
- When treatment can be reduced or stopped
- Combination therapies
- Direct comparisons between preventive treatments
The goal: better results with less trial and error and treatment burden.
What Do These Findings Mean for People With Migraine?
There are more preventative options to work with, but that doesn’t mean the most recent option is necessarily the best one. Doctors may consider:
- Migraine frequency and severity
- Episodic or chronic migraine
- Previous treatment response
- Other health conditions
- Side effects and drug interactions
- Cost and availability
- Patient preference
The objective of preventive therapy is to reduce the frequency at which migraines strike. Your health professional may be in a position to suggest the right form of therapy for you.
Bottom Line
New migraine treatments for long-term prevention are offering patients more choices, while the 2026 studies indicate that some patients can still gain from their use for two years or more. Nonetheless, the long-term effects are under development at the moment.
Medical Disclaimer
This article is intended for informational use only and is not meant to be a substitute for personal medical advice. Migraine medications can cause side effects, contraindications, and drug interactions, as well as have changed uses in approval. Any person suffering from recurring, severe, sudden, or new-onset headaches should consult a medical professional.
References
- Caronna E, Mas-de-Les-Valls R, Egeo G, et al. Neurology. 2026;106(4):e214659. doi:10.1212/WNL.0000000000214659.
- Suzuki K, Suzuki S, Kobayashi S, et al. Cephalalgia. 2026;46(6). doi:10.1177/03331024261453284.
- Kasai K, Yasumoto S, Kosuge M, et al. Frontiers in Neurology. 2026.
- Anti-CGRP Monoclonal Antibodies in Chronic Migraine With Medication-Overuse Headache: Systematic Review and Meta-Analysis. Arquivos de Neuro-Psiquiatria. 2026;84(3).
- Charles AC, et al. Headache. 2024. American Headache Society position statement on CGRP-targeting therapies.
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Md. Rakibul Hasan, BSc (Hons), MS (Thesis)
Biochemistry & Molecular Biology, University of Chittagong, Bangladesh
Senior Biochemist | Health Content Writer | Evidence-Informed Health Information Creator
Popular Diagnostic Centre Limited, Bangladesh.
He specializes in clinical biochemistry, laboratory diagnostics, and medical testing. Alongside his professional work, he is actively involved in health education and scientific communication.
As a Health Content Writer and Research-Based Health Information Creator, he simplifies complex medical and biochemical topics into clear, evidence-informed, and reader-friendly health information.
