I recently saw a 30-year-old patient in my office who was diagnosed with relapsing multiple sclerosis in 2016. She was put on PEGylated interferon-beta 1a due to moderate disease activity. Since then, no clinical relapses have occurred, nor has new activity been detected in the MRI. The patient herself stated that she felt good and had no problems in everyday life. Overall, it is therefore a very stable course, the therapy goal – namely freedom from disease activity – was achieved. Nevertheless, the patient was rather dissatisfied – she no longer saw the point of regularly injecting herself, she was unsure whether the medication would bring anything at all and overall she perceived the permanent use of the medication as harmful.
In principle, I understand the concerns of my patient – the long-term use of MS medications demands a lot from patients. The interferon therapy with the problems of flu-like side effects and injection reactions are a challenge. I also understand the basic wish of a young patient not to have to use medication.
The “Prevention Paradox”
On the other hand, this case also reveals a problem that we frequently encounter argumentatively during the corona pandemic. It can be broadly referred to as the “prevention paradox”: preventive measures that successfully take effect, such as the interferon preparation for the treatment of MS, make the problem (the MS) appear smaller than it is.
On the one hand, we know from prospective studies that even moderately effective MS medications such as interferons have a long-term positive effect on the course of the disease. These older data from the early 2000s could also be confirmed with current data from large registry studies. On the other hand, we know from case-control studies that the original disease activity returns after stopping MS medications. This also applies to moderately effective medications such as interferons and glatiramer acetate. In addition, there is long-term safety data for the aforementioned drug classes, which prove that the aforementioned substances hardly pose a risk with long-term use. From a medical point of view, they thus have a good benefit-risk ratio.
Therefore, the obvious recommendation would be to continue the therapy. However, as already mentioned above, one should not simply disregard the patient’s wishes. Therefore, the current guidelines – like the previous versions – also include recommendations for stopping therapy. It says: “In patients who show only low disease activity before starting immunotherapy and show no disease activity under the previous therapy with a drug of effectiveness category 1, a therapy break can be considered after a period of at least five years if the patient wishes. Patients should be informed that the five-year period is not evidence-based and there are no controlled discontinuation studies that can reliably assess the disease risk after discontinuation.”
Results of controlled discontinuation studies are lacking
We are therefore looking forward to the results of the controlled discontinuation studies. Perhaps then it will be possible to take a clearer position on the issue of discontinuing therapy. Until then, the statement in the guidelines can at least be a help. Accordingly, one could give in to the wish of my patient, who has now been treated for more than 5 years with a preparation of effectiveness category 1 and apparently showed no too high disease activity before initiating immunotherapy, and try to discontinue.
However, I would insist on closely monitoring the further course clinically and with MRI. If activity shows up again, or if other parameters of the disease change, such as fatigue, resuming therapy should be discussed. In addition, I would also make a point about age. At 30 years old, autoimmune diseases are often still very active and you have to live with the disease for a long time. Therefore, I see discontinuing therapy in younger patients as much more critical than discontinuing it at an older age (studies often define this as > 45 years).
Accordingly, I advised my patient to think very carefully about discontinuing therapy. Because actually the therapy achieved exactly what we had wished for. And she has many years ahead of her in which the disease can be active. I am curious to see what she will ultimately decide…
Tolerance problems are solvable
And it should be mentioned at this point that tolerance problems with a substance should always be addressed openly and taken seriously. But the solution here should not be to stop, but to switch to a better-tolerated substance. And here we benefit from the wide range of different therapies. Tolerance problems should nowadays not be a reason for stopping an effective therapy.
