A study led by Vall d’Hebron, carried out at the Multiple Sclerosis Centre of Catalonia (Cemcat), has analysed the risk of reactivation of multiple sclerosis after interrupting disease-modifying treatments. The results show that stopping treatment increases the risk of presenting inflammatory activity, mainly detectable by magnetic resonance imaging, but this effect is considerably reduced in people over 60 years of age. The study has been published in the Journal of Neurology, Neurosurgery & Psychiatry.

Disease-modifying treatments (DMTs, for their initials in English) are a fundamental part of the treatment of multiple sclerosis, as they reduce inflammatory activity and the risk of new lesions and relapses. However, with age, the inflammatory activity of the disease tends to decrease, while some of the risks associated with some treatments, such as infections, increase. For this reason, in older people with stable disease, the possibility of interrupting treatment is increasingly being considered.

“In older people with multiple sclerosis, we are faced with a complex clinical decision: to continue a treatment that may have less benefit as age advances, but which may also involve risks, or to interrupt it while assuming the possibility that disease activity may reappear. This study helps us identify which factors may be more important when making this decision,” explains Dr René Carvajal, first author of the study and researcher in the Vall d’Hebron Research Institute (VHIR) Clinical Neuroimmunology group and at Cemcat.

There is more inflammatory activity after interrupting treatment

To study this, the research team analysed data from 563 people with multiple sclerosis aged 50 years or older who had received disease-modifying treatment. Of these, 113 interrupted treatment. The researchers compared these people with a group of patients with similar characteristics who continued therapy, taking into account factors such as age, sex, type of treatment, duration of the disease, the length of time since they had presented inflammatory activity and degree of disability.

The results show that people who interrupted treatment had approximately twice the risk of subsequently presenting inflammatory activity. This activity was detected mainly through magnetic resonance imaging, with the appearance of new lesions, and not necessarily through new relapses or symptoms.

Specifically, inflammatory activity was observed on magnetic resonance imaging in 24.7% of people who interrupted treatment, compared with 13.6% of those who continued it. Relapse rates, on the other hand, were similar between the two groups.

The risk of reactivation decreases after the age of 60

One of the main results of the study is that age significantly modifies the risk associated with interrupting treatment. In people aged 60 years or younger, interrupting treatment was associated with an almost four times higher risk of inflammatory reactivation than continuing it. In contrast, in people over 60 years of age, this increase in risk was much lower.

“The results suggest that age is a particularly relevant factor when assessing a possible interruption of treatment. This does not mean that from the age of 60 onwards it is advisable to stop it, but rather that the risk of inflammatory reactivation associated with withdrawal appears to be lower. The decision must be made on an individualised basis, also taking into account the type of treatment, previous disease activity and the characteristics of each patient,” highlights Dr Mar Tintoré, clinical head of the Neurology Department of Vall d’Hebron University Hospital and Cemcat, and principal investigator of the VHIR Clinical Neuroimmunology group.

The study has also analysed whether the length of time that patients had remained stable before interrupting treatment modified the risk of reactivation. Although most patients had been several years without relapses or activity on magnetic resonance imaging, the duration of this period of stability was not independently associated with a lower risk of reactivation. This suggests that age and type of treatment may be more informative factors than the simple number of years of stability.

Anti-CD20 treatments show low activity after interruption

The researchers also observed differences according to the type of treatment. In people who interrupted anti-CD20 treatments, such as ocrelizumab, rituximab or ofatumumab, no relapses were recorded during follow-up and 8.7% presented activity on magnetic resonance imaging. In comparison, activity on magnetic resonance imaging was 27.3% after interrupting first-line treatments.

These results should be interpreted with caution, since the number of people who interrupted some types of treatment, especially anti-CD20 and anti-trafficking treatments, was small. For this reason, the authors point out the need for larger cohorts to confirm these differences.

No significant differences in the progression of disability in the medium term

Another of the objectives of the study was to determine whether interrupting treatment was associated with greater progression of disability. During the follow-up period analysed, no statistically significant differences were observed between people who interrupted treatment and those who continued it.

Nevertheless, the researchers observed a numerically higher proportion of worsening of disability among people who had interrupted treatment (38.2% compared with 30.5%). Therefore, the results do not allow us to rule out that interruption may have consequences on the progression of disability in the longer term, especially because in older people this progression may be related to mechanisms independent of inflammation.

The authors consider that the results may contribute to advancing towards more individualised treatment strategies in older people with multiple sclerosis, balancing the potential benefits of disease-modifying treatments with the risks associated with their prolonged use. In any case, they point out that studies with longer follow-up are necessary to determine the impact of treatment interruption on the progression of disability in the long term.