Interferons are the “original substances” for the treatment of Multiple Sclerosis. In 1993, Interferon-beta 1b (Betaferon®) from Schering (now part of the Bayer Group) was the first modern immunotherapy to be approved for MS. This was a milestone for MS therapy. Despite their clear effect on the course of Multiple Sclerosis, interferons were not without controversy among MS patients. This is primarily due to the frequent injections (every 2nd day with Betaferon) and the specific tolerability problems of the interferons. In addition, it has damaged the reputation of interferons that they were used in the 90s mainly late in the course of the disease. At this stage, they can no longer show particularly good effects. It was only later that early therapy studies with the different interferon preparations demonstrated the good prophylactic potential of interferons. This has significantly changed the prescribing behavior. The interferons became a classic first-line therapy for mild/moderate MS and were often used after the first clinical relapse.
Interferons beta 1a and 1b
After Betaferon® was approved in 1997, Interferon beta 1a (Avonex®) became another approved interferon preparation. Due to its once-weekly intramuscular administration, it was more patient-friendly. Finally, in 1998, another Interferon-beta 1a preparation for subcutaneous use (Rebif®) was approved. Rebif® is available in two different dosages (22 and 44 µg) that need to be injected three times a week. The 22 µg dosage plays a minor role in long-term therapy due to its weaker effect compared to the 44 µg dose. If possible, 3 x 44 µg per week should be given. The range of interferons is completed by Extavia®. It is an Interferon-beta 1b preparation identical to Betaferon®. In 2014, Plegridy®, the first pegylated interferon (PEG-interferon), came onto the market. Due to the pegylation, which results in a delayed release of the active ingredient, it only needs to be injected every 2 weeks. Plegridy was approved as a subcutaneous drug in 2014, but now also has approval for intramuscular administration. Since Plegridy® is a further development that has some special features compared to the non-pegylated interferons, I will write a separate text for this medication.
The following explanations therefore refer to the non-pegylated interferons. They all have in common that they are given as injection therapy. Therefore, they are difficult to use for people who have a fear of injections. Understandably, alternatives should be sought here.
Side effects of interferons
All interferons have reactions at the injection site as a significant side effect. These are more pronounced with the subcutaneously administered preparations than with the intramuscular administration of Avonex® – but can also occur here. In the case of subcutaneous administration (Betaferon®, Extavia®, Rebif®), the local reaction at the injection site is accompanied by redness, pain and itching. Sometimes there is a local inflammatory reaction up to – in rare cases – ulcerations or even necroses of the skin. Disinfection of the injection site and cooling after injection is helpful to reduce the occurrence and extent of local injection reactions. In addition, the subcutaneous injection sites should be changed from injection to injection to protect the skin. Also, warming the injection to room temperature can be useful to reduce reactions at the injection site.
Another main side effect of interferons are flu-like side effects, which can occur about 2 hours after injection of all interferon preparations. In clinical studies, every third study patient reported flu-like side effects such as headaches, muscle pain, chills or fever. These complaints are more common at the beginning of therapy and usually decrease with continued injections. Therefore, a slow dosing of the interferon at the beginning of therapy can help alleviate the flu-like symptoms. To improve tolerability, every patient starting with an interferon should be recommended prophylactic and accompanying treatment with anti-inflammatory drugs (e.g. ibuprofen 400 mg, paracetamol 500 mg). In addition, it makes sense to administer the interferon in the evening so that, ideally, you “sleep through” the flu-like side effects.
Not suitable for depression
The package insert of interferon preparations lists a whole range of potential side effects. They play no special role in practice, with a few exceptions. An exception is depression. It is known that interferons can intensify a depression. Therefore, their use is contraindicated in severe depression and/or suicidality. However, this side effect should also be considered if a patient develops an increasingly depressed mood under the medication. Here, a change of preparation could possibly help. Interferon can also cause changes in the blood count and lead to elevated liver values – therefore regular laboratory control is also indicated for these substances.
Otherwise, it is a great advantage that interferons have been available for almost 30 years in MS therapy and no significant safety signals have occurred during this long period. The interferons do have relevant tolerability problems, but ultimately no serious medical side effects.
This is also evident from the fact that interferons have now also been approved for use during pregnancy and lactation.
