CGRP monoclonal antibodies - Pain Clinic Kiel

CGRP monoclonal antibodies: immunotherapy for migraine

Erenumab

Erenumab (Aimovig®) is a monoclonal antibody that inhibits the CGRP receptor. CGRP is considered to play an important role in the pathophysiology of migraine. Increased CGRP levels are found in migraine attacks, and in chronic migraines also between attacks. Intravenous administration of CGRP can cause migraine-like headaches in migraine patients. The triptans, which are effective in acute migraine therapy, inhibit the release of CGRP. Finally, the so-called Gepanten was able to show that by inhibiting the CGRP receptor, migraine attacks can be interrupted acutely and, if taken regularly, they can be prevented.

Aimovig® was approved by the US Food and Drug Administration (FDA) in May 2018 for the preventive treatment of migraines in adults. Treatment is carried out by self-injecting the drug under the skin once a month. Aimovig is the first approved preventative migraine medication in a new class of drugs to prevent migraines. They work by inhibiting the activity of calcitonin gene-related peptide (CGRP). The molecule is involved in the development of migraine attacks.

effectiveness

In the approval studies, erenumab was able to reduce the number of migraine days per month significantly more than placebo in both patients with episodic and chronic migraine and who had previously had no success with a maximum of two (for episodic migraine) or a maximum of three (for chronic migraine) migraine prophylactics. The 50% responder rate was significantly higher than with placebo, the use of acute medication was significantly lower and there was a significant improvement in quality of life.

In the STRIVE study (Phase 3) in episodic migraine, 70 mg erenumab and 140 mg erenumab were tested against placebo. The 50% responder rates (number of subjects with a reduction of migraine days/month by at least 50%) were 43.3% for 70 mg erenumab, 50.0% for 140 mg erenumab and 26.6% for placebo. The difference between erenumab 70 and 140 mg was not significant. In chronic migraine (phase 2), similar 50% responder rates were achieved: 40% for 70 mg erenumab, 41% for 140 mg erenumab and 23% for placebo.

Since no study has been carried out against one of the standard substances for migraine prophylaxis, the proof of additional benefit required for erenumab to be reimbursed in the statutory health insurance system is based on the LIBERTY study.

Here, patients with episodic migraine (four to 14 migraine days/month) and previous treatment failure with two to four standard migraine prophylactics were treated with 140 mg erenumab or placebo. The responder rate to erenumab 140 mg was 30% and that to placebo was 14%; the difference was statistically significant. The number of migraine days per month decreased by 1.76 days with erenumab (output 9.3 days/month) and by 0.15 days with placebo. Here too, the difference between erenumab and placebo was statistically significant.

In an analysis of effectiveness at the Headache Center of the Kiel Pain Clinic between November 2018 and December 2019, a total of 193 patients with erenumab were evaluated who had so far proven to be refractory to beta receptor blockers (metoprolol or propranolol), amitriptyline, topiramate, flunarizine, valproate and onabotulinum toxin for chronic migraines or for whom a contraindication precluded its use. The 50% responder rate was 38% in patients with episodic migraine (n=48). For patients with chronic migraine (n=145), a 50% responder rate was found in 33% of patients. Around three quarters of the patients received a dosage of 140 mg erenumab. Overall, the effectiveness rates were somewhat lower than in the study patients without multiple therapy failure, but for episodic migraine they were higher than in the Liberty study (38% versus 30%). Experience suggests that the results of the controlled studies can be transferred to everyday clinical practice. Approximately one in three affected people, who have so far only been able to receive inadequate prophylactic medication, benefits significantly.

Use after approval and according to AMNOG procedures

Erenumab is approved for migraine prevention in adults with at least four migraine days per month.

The regulation must also take economic efficiency into account. The medication costs around 495 euros per month (as of March 2021) and is many times more expensive than previous preventative medications. The economic viability is checked in the so-called AMNOG process.

AMNOG means “Medicine Market Reorganization Act” and aims to regulate the price of innovative drugs in Germany. The procedure has been regulating the prices of new, patent-protected drugs since January 2011. The basis is the additional benefit assessment. This means that health insurance companies only pay the price that corresponds to the determined additional benefits of the drug. The goal is a balance between innovation and affordability.

The AMNOG procedure for assessing the cost-effectiveness of a new therapeutic procedure has no influence on the approval status of a drug, as listed in the specialist information. However, due to the cost-effectiveness requirement according to §12 SGB V, a regulation according to the G-BA decision should only be made if a more cost-effective alternative is no longer available. This applies as long as there is no proven additional benefit for erenumab compared to standard prophylactics that would justify the significantly higher treatment costs.

Due to the G-BA decision, erenumab can actually only be prescribed at the expense of statutory health insurance under the following conditions, despite broad approval:

Conditions for prescribing CGRP monoclonal antibodies to prevent migraines at the expense of statutory health insurance

Age ≥ 18 years
Migraine frequency ≥ four days per month
Initiation of treatment by physicians experienced in diagnosing and treating migraines.
Ineffectiveness, intolerance of metoprolol or propranolol, amitriptyline, topiramate, flunarizine and valproate as well as additional onabotulinum toxin in chronic migraines or the substances are contraindicated for the patient

The 4th condition means a clear restriction that is economically justified. In return, erenumab was given the status of a nationwide practice specificity in the AMNOG procedure. If the four conditions mentioned are met, the prescriber's drug guarantee volume will be adjusted for the costs of erenumab from December 15, 2019. Depending on the statutory health insurance association, this is done in advance or subsequently.

Erenumab usually takes effect in the first four weeks, but at least within three months. If there is no response to the treatment after three months of treatment, a subsequent prescription is no longer covered by the practice specificity and the treatment should be stopped. It is therefore the prescriber's obligation to carefully and continuously quantitatively document the patient's response.

The AMNOG procedure does not specify when a response to therapy can be assumed. It would be objectively justified to use the 50% responder rate, analogous to the effectiveness parameters in the approval studies. A response would be proven individually if the number of migraine days per month was at least halved.

In addition, the AMNOG procedure stipulated that, contrary to what is prescribed in the product information, not only the initiation but also the monitoring of treatment with erenumab should be carried out by doctors who have experience in the diagnosis and treatment of migraine.

The SmPC lists the side effects recorded in the studies as reactions at the injection site (5.6% for 70 mg erenumab or 4.5% for 140 mg erenumab), constipation (1.3% or 3.2%), muscle spasms (0.7% or 2.0%) and Pruritus (1.0% and 1.8% respectively). Most of these side effects were mild or moderate in severity. Less than 2% of patients in the studies discontinued participation due to adverse events. The tolerability of erenumab in the patient population examined can therefore be described as very good.

According to the specialist information (as of August 2018), the only contraindication is hypersensitivity to the active ingredient erenumab or one of the other ingredients. However, in the section “Special warnings and precautions for use” there is a note that patients with certain serious cardiovascular diseases were excluded from participation in the clinical studies. There are no safety data available for these patients. At this time, the use of erenumab in patients with cardiovascular disease should be undertaken with increased caution.

Due to the biological effect of CGRP, the use of monoclonal antibodies for migraine prophylaxis is not recommended in the following conditions:

pregnancy
lactation
Inadequate/lack of contraception
coronary heart disease
stroke
Cerebral hemorrhage
peripheral arterial disease
inflammatory bowel diseases
COPD
pulmonary hypertension
M. Raynaud
Wound healing disorders
Transplant recipients

In principle, since the available studies have so far only included patients without relevant previous illnesses, appropriate caution should be exercised in patients with chronic concomitant illnesses.

dosage

Erenumab is currently available in Germany as an auto-injector at 70 mg and 140 mg. The price of both dosages is identical. In the studies that directly compared the 70 mg and 140 mg doses, there was no significant difference in effectiveness. Only the frequency of the side effect constipation increased with the higher dose. However, in the LIBERTY study, only the 140 mg dose was tested against placebo in patients with episodic migraine and multiple therapy failure with standard prophylactics. The specialist information also points out that the patients in the chronic migraine study who had already stopped two or three previous therapies would have benefited more often from the 140 mg dose. According to the product information, the recommended dose is 70 mg erenumab every four weeks. However, some patients may benefit from a dose of 140 mg every four weeks. If the effect and tolerability are insufficient, a dose increase to 140 mg can be discussed.

Duration of treatment

According to the product information, discontinuation of treatment with erenumab should be considered after three months if there has not been an adequate response by then.

The majority of patients who responded to therapy experienced clinical benefit within three months. Keeping digital headache documentation has proven to be beneficial for assessing response. The migraine app for iOS or Android has proven useful for clinical care, as it provides a direct quantitative analysis of the course and at the same time provides extensive information and non-drug therapy options.

Goal of treatment

There is no operational definition of the target parameter “response” in the specialist information. It is also unclear when a possible dose increase from 70 to 140 mg should take place. In the studies, a 50% reduction in migraine days per month was chosen as a measure of effectiveness. This specification is also suitable in everyday clinical practice when treating episodic migraines. However, if chronic migraine is present and the disease is otherwise refractory to treatment, a reduction in migraine days by 30% per month should be considered a clinically relevant response. However, for a patient, a decrease in migraine pain intensity also represents a significant improvement. If the frequency of migraines does not decrease significantly, but the intake of painkillers and/or triptans decreases by 50% for episodic migraines or 30% for chronic migraines, then from a clinical perspective a response to treatment can be assumed.

Onset of action

A key difference between erenumab and standard oral prophylactics is its rapid onset of action. The study data shows a significant effect after just one month. Conversely, there is no further significant improvement after the first two months; the effect achieved remains stable. Treatment should not be continued for longer than a total of three months if the stated effectiveness goals have not been achieved. This would then mean a maximum duration of taking erenumab of three months if it is ineffective.

Review of the need for long-term treatment

The specialist information also recommends assessing at regular intervals, even after the first three months of treatment, whether treatment should be continued. This means that sustained effectiveness, which alone justifies continuing treatment, must also be documented. The easiest way is to use the migraine app, which aggregates the effectiveness data over time and makes it objectively available. In the erenumab studies, patients were offered further treatment with erenumab in open study extension phases following the double-blind study phases. The long-term data obtained in this way, which has now spanned five years, demonstrate the consistently good effectiveness and tolerability of erenumab. Unfortunately, data on the spontaneous progression of migraines after discontinuation of erenumab were unfortunately not collected. At this point, it is unclear how long successful treatment with erenumab should be continued.

The technical information does not provide for a time limit for effective therapy with a monoclonal antibody for migraine prophylaxis. The same applies to the regulation of the nationwide practice specificity. Therapy should only be stopped after three months at the latest if adequate response is not documented.

In contrast, the addendum to the guidelines of the German Society for Neurology explicitly suggests: If the therapy is effective, an attempt to stop it should be made after six to nine months to check whether the therapy is still necessary.

This even goes beyond the general recommendation for the use of migraine prophylactics, which states that successful migraine prophylaxis should be checked for its necessity after six to 12 months by reducing the dose or discontinuing it. The reason given is that in the antibody studies in which the effectiveness was further recorded after treatment was stopped, a deterioration occurred again after five to 20 weeks, but the initial values had not yet been reached again.

An interruption of effective treatment with a monoclonal antibody for migraine prophylaxis after a certain point in time is therefore not formally necessary according to the specialist information/special practice regulations, but is merely a suggested guideline. In addition to general economic reasons, there are also medical reasons for an interruption. In addition to the question of why treatment that may no longer be necessary should be continued, it is also reasonable to ask why treatment that may no longer be necessary should be continued, the long-term consequences of which for health cannot yet be foreseen. If the migraine worsens after stopping and taking a break, treatment can be resumed without any problems. However, whether and, if so, when to attempt to eliminate the drug - after six, nine or 12 months - remains at the discretion of the prescriber at this point.

Erenumab: Practical application

According to the specialist information, treatment should be initiated by doctors with experience in migraine diagnosis and treatment. Regular follow-up checks are absolutely necessary (see above) to decide whether to continue treatment. We recommend using the migraine app. The app helps, among other things, to adhere to individual rules for headache treatment, to avoid complications such as medication overuse headaches and provides non-medicinal treatment options such as progressive muscle relaxation.

Around 50% of patients with more than 15 headache days per month for at least three months have, in addition to the original primary form of headache, a further causal reason for the increasing frequency of headache days, medication overuse headache (MÜK). In contrast to the initial situation, most of those affected show a reduction in the number of headache days per month after a medication break and a renewed response to preventive and acute medication. Advice on this, knowledge of the connection and consequences of medication overuse headache (MÜK) are therefore essential. Patients with medication overuse headache (MOH) should take an adequate medication break before initiating treatment with erenumab and be encouraged to adhere to the 10-20 rule: painkillers and specific migraine medications should be used less than 10 days per month, and at least 20 days per month be completely free from taking them.

The injections are carried out using an auto-injector at intervals of four weeks. Many migraine patients are familiar with using this auto-injector, as an almost identical pen is also used for the subcutaneous administration of sumatriptan sc. In contrast, the pen is not used in the attack when necessary. Rather, it is used at fixed intervals of four weeks (ie 28 days) for prevention according to a defined treatment plan. This immunotherapy is a passive immunization. The antibodies are not produced in the human body themselves, but are produced in the laboratory as a fully human monoclonal IgG2 antibody in Chinese hamster ovary (CHO) cells using recombinant DNA technology. For this reason, the dose must be repeated regularly. Immunotherapy or passive “vaccination” does not mean that the disease no longer occurs. The risk of future attacks is reduced. During the dosing period, erenumab is eliminated primarily via a non-specific protein-metabolizing pathway and has an elimination half-life of approximately 28 days.

Erenumab is administered subcutaneously by the patients themselves. The injection can be given on the stomach, thigh, or outside of the upper arm. A different injection site should be used for each subsequent injection. Injections should not be given into sensitive, injured, red or hard areas of skin. The autoinjector is for single use. As a precaution, erenumab should be avoided during pregnancy. It is therefore important to ensure adequate pregnancy prevention.

The medicine should be stored in the refrigerator at 2-8 degrees Celsius and should not be frozen. The autoinjector should be stored in the outer box, protected from light. If the medicine is stored at room temperature up to 25 degrees Celsius, it must be used within 14 days or disposed of. Before use, the solution should be inspected visually. If it contains cloudiness, flakes, particles or a yellow discoloration, it must not be used. To avoid discomfort at the injection site, the autoinjector should be removed from the refrigerator prior to injection and stored at room temperature for at least 30 minutes, avoiding shaking and direct sunlight or other heat sources.

A slow dosage increase due to possible intolerances and side effects is not necessary. If there is a response, the onset of action can be expected quickly, initially within a few days. Side effects of previous migraine preventatives such as weight gain, mood changes, fatigue, reduced drive or drowsiness are not to be expected. However, the data available so far shows that one should not assume that the new active principle will stop migraines and that one can live as one wants. Around 70% of patients with episodic migraine who have previously failed other therapy attempts will probably not respond to the new mechanism of action. It is not yet possible to predict who will be among the 30% responders.

Fremanezumab

The monoclonal antibody against CGRP, fremanezumab (Ajovy®), was also recommended for approval by the EMA's Human Medicines Committee on January 31, 2019 and approved by the European Commission in April 2019.

Ajovy® differs from Aimovig® and Emgality®, among other things, in the application interval: quarterly application is available in addition to monthly.

Fremanezumab was studied in a total of 2,000 patients in pivotal studies. The phase III Halo EM study examined patients with episodic migraine and the phase III Halo CM study examined patients with chronic migraine. The Halo CM study compared the effectiveness of 225 mg fremanezumab in monthly doses and 675 mg fremanezumab in quarterly doses compared to placebo in 1,130 patients. On average, patients suffered from migraines on 13.2 days per month (monthly fremanezumab group), 12.8 days per month (quarterly fremanezumab administration), and 13.3 migraine days per month (placebo group). In the group of patients receiving quarterly fremanezumab, 675 mg of fremanezumab was initially administered subcutaneously. After a period of 4 and 8 weeks, placebo doses were used. Patients receiving monthly fremanezumab were treated with a starting dose of 675 mg fremanezumab. They then received 225 mg of fremanezumab at week four and week eight. The main outcome measure was the reduction in average headache days per month. A headache day was defined by at least four hours of discomfort per day or the use of migraine-specific acute medication per day.

The most significant reduction was observed in the monthly dosing group. In this group, patients had an average of 4.6 fewer days of migraines per month. 41% of patients achieved a halving of headache days per month with this application method.
When fremanezumab was administered three months apart, an improvement in monthly migraine days of 4.3 days was observed. In this group, 38% of patients achieved a 50% reduction in headache days.
In comparison, a reduction in headache days per month of only 2.5 days was found in the placebo group. 18% in the placebo group showed a halving of headache days per month.

The approval text envisages the use of fremanezumab (as well as erenumab and galcanezumab) in adult patients who suffer from migraines on at least four days per month.

Fremanezumab is the only antibody available to date that has demonstrated significant effectiveness even when administered quarterly at 675 mg in three times the monthly dose of 225 mg

The antibodies are approved for the preventive treatment of both episodic and chronic migraines. Fremanezumab is the only antibody available to date that has demonstrated significant effectiveness even when administered quarterly at 675 mg in three times the monthly dose of 225 mg. There is currently no special three-month syringe available that allows patients to receive the corresponding dose of 675 mg in just one application. Therefore, even with three months of use, patients currently have to use three injections, albeit at a single time.

The most common undesirable side effect was pain at the injection site. These did not differ significantly between the group treated with fremanezumab or placebo.

When using it to prevent migraines, some basic features must be taken into account:

Monoclonal antibodies are expensive drugs. There are currently no comparative studies on previous guideline-based preventative migraine medications. If you compare the effectiveness data with the previous active ingredients, the average values do not show any particular superiority in terms of effectiveness. The special additional benefit lies in the fact that patients who did not respond to the previously available drugs, who had contraindications or who could not tolerate them, can still achieve effectiveness with the monoclonal antibodies. For reasons of cost-effectiveness, the new treatment options will therefore have to be used for patients for whom the previous guideline-based migraine prophylactics were not helpful.
The monoclonal antibody must be administered as an injection under the skin using an autoinjector.
The monoclonal antibody has a very long duration of action with a half-life of approximately four weeks. This means that after a month, around 50% of the active ingredient is still circulating in the bloodstream and is active. Since this is a very new class of medication, long-term effects from prolonged use cannot yet be assessed with certainty.
Immunotherapy for the preventive treatment of migraines is not a “final cure” for migraines. Only about 30% of patients who have not responded adequately to previous preventative treatment measures can expect a reduction in migraine attacks by 50% or more. This effect is unlikely to occur in 70% of treated patients. A majority of patients who achieve this effectiveness will still experience migraine attacks that require acute medication treatment.

Galcanezumab

After erenumab (Aimovig®) on November 1, 2018, the monoclonal antibody galcanezumab (Emgality®) for migraine prophylaxis also became available in Germany from April 1, 2019. Galcanezumab has been approved in the EU since November 2018. Approved to prevent migraines in adults who suffer from migraine attacks on at least four days a month. Galcanezumab is approved for the prevention of migraines in adults who experience migraine attacks on at least four days per month.

Galcanezumab is a humanized monoclonal antibody. In contrast to erenumab, galcanezumab and fremanezumab do not work indirectly by inhibiting the CGRP receptor. They neutralize the messenger CGRP directly.

At the beginning of the treatment, a so-called loading dose of 240 mg is administered. A further injection of 120 mg is then given every month.

Similar to erenumab, galcanezumab is administered by patients themselves through a subcutaneous injection using an autoinjector. Initially, a so-called loading dose of 240 mg is administered. A further injection of 120 mg is then given every month.

Galcanezumab was studied in three large Phase 3 trials, Evolve 1, Evolve 2 and Regain.

The main finding in the Evolve 1 study with 858 patients was that 62.3% of patients were able to halve their monthly headache days by at least 50%. When given a placebo (dummy preparation), this effect was achieved in 38.6% of patients.

In Evolve 2, when 915 patients were included, 59.3% of patients treated with galcanezumab halved their monthly headache days with galcanezumab. The administration of placebo resulted in halving the number of headache days per month in 36%. On average, the patients who received 120 mg of galcanezumab experienced 4.3 fewer migraine days per month; those who received placebo experienced a reduction of 2.3 fewer days per month. The baseline in the group treated with galcanezumab was 9.1 migraine days per month and in the placebo group 9.2 migraine days per month.

The Regain study examined patients with chronic migraines. There was a reduction in monthly headache days under galcanezumab by 4.8 days from 19.4 days. When treated with placebo, there was a reduction in headache days per month by 2.7 days, starting from 19.6 days before the start of treatment.

The tolerability of galcanezumab was similar to the tolerability of placebo.

The medication Emgality® is provided as a ready-made pen. The pack sizes each contain two or three auto-injectors. Patients can use this auto-injector to inject the medication under the skin themselves. The medication can be administered under the skin on the stomach, thigh, upper arm, or buttock area.

The AMNOG procedure, which is important for clinical use for the monoclonal antibodies galcanezumab (Emgality®) and fremanezumab (Ajovy®), which were approved in 2019, had not yet been completed at the end of the manuscript.

Based on the positive benefit assessment, a nationwide practice special was also agreed for Emgality®. This nationwide practice special applies from April 1, 2020, but only for the patient group for which the significant additional benefit was decided.

On September 19, 2019, the G-BA found a considerable additional benefit for Emgality®. This applies to patients who do not respond to any of the following therapies or drug classes, who are not suitable for them or who cannot tolerate them: metoprolol/propranolol, flunarizine, topiramate, amitriptyline, valproic acid, Clostridium botulinum toxin type A (for chronic migraines) .

CGRP monoclonal antibodies: possibilities and limitations

What is the additional benefit compared to previous therapies?

Whether a new drug is better than the previous ones can be seen by comparing its effectiveness, tolerability and safety. To compare the effectiveness of medications for migraine prophylaxis, studies usually use the reduction in migraine days per month. However, if you compare the average values of different active ingredients with the administration of a placebo, there is only a reduction of one to four days per month. This sounds sobering at first - especially for patients who experience 15 or more migraine days per month. However, these are average values that are used solely to examine the statistical superiority of a substance over a placebo. The calculation includes both patients who respond very well to the treatment and others for whom it does not work at all. Studies on the effectiveness of CGRP antibodies now show a similar effectiveness to the active ingredients previously approved for migraine prevention. The reduction in migraine days per month is approximately one to three migraine days. On average, the CGRP antibodies do not show any better effectiveness than the previously approved drugs. Therefore, in terms of effectiveness, there is no proven additional benefit for patients who are already responding to previous prophylactics. The Federal Joint Committee (G-BA) also found this. However, things are different if patients do not respond to the current medication, cannot tolerate it or have contraindications. This means that medications may not be taken due to other illnesses, for example.

How do the CGRP antibodies work in these patients?

In this situation, CGRP antibodies may have an effect in about a third of patients. Accordingly, the G-BA found a considerable additional benefit for CGRP antibodies in adult patients with at least four migraine days per month in whom standard prophylactics were ineffective, intolerable or contraindicated. The CGRP antibodies have further special features: slow dosage is not necessary. A quick effect can be expected - this is important for many patients and promotes adherence to therapy.

Which patients in this group, for whom previous medications have not helped, will respond to the new antibodies?

It is impossible to predict on an individual basis which patients will respond to treatment in whom standard prophylactics were previously ineffective, intolerable or contraindicated. Each of these patients has the same approximately 30% chance of reducing migraine days. At the same time, this also means that the antibodies do not respond in around 70% of patients. It is therefore necessary to closely monitor the success of therapy. If no significant effect is achieved after three months, therapy should not be continued. Digital care applications such as the migraine app can also be used to monitor therapy and progress.

Does it make sense to switch between CGRP antibodies if the first one has not shown any effectiveness?

To date, there are no controlled studies that prove that switching can be successful if another antibody has not worked. There is practically no significant difference between the three antibodies in terms of their effectiveness compared to placebos; direct comparisons are still missing.

How is it tolerated in everyday clinical practice?

Common side effects include hypersensitivity reactions such as rash, swelling and edema in the area of the injection site, itching or muscle cramps. On the other hand, side effects such as weight gain, mood changes, fatigue, cognitive deficits or dizziness usually do not occur when using CGRP antibodies. According to current knowledge, they are well tolerated.

Can patients completely get rid of migraines with the new medications?

Many patients hope that with a specific treatment they can stop migraines once and for all and then live as they want. However, this is an illusion - this is what the numbers I have described show. The treatments help to reduce some of the attacks. The antibodies can only have an effect on the mechanisms that trigger migraines. It is essential for those affected to adapt their lives to their particular risk tolerance for migraine attacks. Even when using antibodies, extensive knowledge of the clinical picture and specific prevention through an adapted lifestyle are essential.

Do the CGRP antibodies also work on other types of headaches?

In the EU, CGRP antibodies have so far only been approved for the preventative treatment of migraines. The antibody galcanezumab has also been proven to be effective in preventing episodic cluster headaches - it is already approved for this purpose in the USA. The European regulatory authority has not promised approval for this application. There is no approval for use in headaches caused by medication overuse. Before antibodies are used, this form of headache should therefore be treated by taking a break from medication.

Can the CGRP antibodies also be used in children?

To date, there are no controlled study data for children and adolescents. Corresponding studies are currently being carried out. It remains to be seen whether antibodies are also effective for these young patients.

How long do patients have to use the CGRP antibodies? For life, or can you stop using them at some point?

There are various target parameters for successful therapy; a specification is made in the DGN guidelines (German Society for Neurology). Therapy is therefore successful if there is a reduction in the average number of monthly headache days by at least 50 percent compared to the previous treatment over a period of at least three months or if there is a significant improvement in the headache symptoms. If a patient achieves these effectiveness parameters, he or she can attempt a withdrawal trial after about nine to twelve months to check whether the therapy is still necessary. This approach is suggested in the DGN guidelines. However, it is not stipulated by the specialist information, the G-BA resolution or the rules on nationwide practice specificity.