Safety and efficacy of DMT in patients with MS over the age of 60

By Dr Svetlana Stamenova, Locum Consultant Neurologist, Salford Royal NHS Foundation Trust

The prevalence of multiple sclerosis (MS) in older age has increased, although disease onset typically occurs in the young. This patient population is understudied and presents with unique challenges, including the prevalence of progressive forms of disease and the safety profile of disease-modifying therapy (DMTs). These patients encounter specific problems such as the changes in renal and hepatic function with age, in addition to the coexistence of medical co-morbidities.

There is no set guidance for discontinuing DMT and whether or not we should treat with immunosuppressant treatment our elderly patient.

The aim of the study was to assess efficacy and safety of DMT in the age above 60.

The study included all the MS patients in our MS centre (Royal London Hospital) who were 60 years or older by the time they were started on DMT. The study included a retrospective review of all relevant demographic and clinical data, including comorbidities, disability scores (as determined by the Expanded Disability Status Scale [EDSS]), previous DMT (reason for discontinuation), DMT compliance and administration, clinical course, side effects, and magnetic resonance imaging (MRI) outcomes such as radiological activity.

In the study were enrolled 34 MS patients started on DMT at the age of 60 or more, with an average age 63 years (median 61.5 years). They were 14 males and 20 females. 53 % of our cohort were patients with progressive disease (including 11 patients with primary progressive (PP) and 7 patients with secondary progressive disease (SP). The rest of the patients (16 patients) were with relapsing-remitting MS (RR). The average EDSS at baseline was 5.5 (median 6.0).

As expected most of the patients were with comorbidities with prevalence of essential hypertension (16 patients) and musculoskeletal disease (such as osteopenia, osteoporosis, low back and joint pain – 9 patients). 32 % of our elderly patients were with 3 comorbidities.

We looked into their past DMT and found out that 53% (18 patients) of our patients were treatment naïve, 17% (6 patients) were previously treated with injectable therapy (Rebif, Betaferon and Avonex), 29% (10 patients) were treated with oral therapy (Dimethyl-fumarate, Teriflunomide and Fingolimod), 14% (5 patients) were treated with infusion therapy (Natalizumab) and 3% (only 1 patient) was previously enrolled in a trial (MS Smart trial). Patient therapy was escalated due to disease progression (41%) or intolerability (59%).

Looking into the DMT profile of the patients aged 60 or more and started on DMT we found out that the majority of the patients (21 patients) were treated with Cladribine sc (off label Cladribine personalised dose). Most of these patients were not eligible according to NHS England criteria for other DMTs. Among the rest of the patients we had 4 patients on Ocrelizumab, 3 on Alemtuzumab, 3 on Natalizumab, 2 on Fingolimod and 1 patient on Mavenclad therapy.

I was pleased to note that 79% (27 patients) did not have side effects during and after treatment. Only 21% (7 patients) developed side effects including recurrent chest infection requiring hospital admission, recurrent UTIs with subsequent urosepsis requiring hospitalisation, ear infection, hypothyroidism , upper respiratory tract infection and flu like illness requiring hospitalisation. Of note all the patients who developed severe adverse events requiring hospital admission were with very high disability (EDSS-8.0). None of the patients discontinue treatment due to side effects and the profile of the reported side effects was similar to the side effects in young adults.

We looked into the radiological and clinical activity in order to assess the efficacy. The clinical course of the disease was considered stable in 53% (18 patients) of our patients. 32 % (11 patients) showed slow progression without relapses, 6% (2 patients) relapsed after the end of the treatments and 3 % (1 patient) was considered having slow progression with acute relapses. The clinical course for 6% (2 patients) were not documented. 38% (13 patients) showed stable EDSS. The discrepancy is due to the fact that 35% (12 patients) did not have documented EDSS.

MRIs outcomes were positive too, as 53% (18 patients) showed stable disease without evidence of radiological progression (no new or enhancing lesions on interval MRI scans). 12% (4 patients) had progression of the disease with evidence of new and/or active GAD enhancing lesions and 26% (12 patients) were without interval scans for comparison.

In conclusion the use of disease-modifying therapy appears relatively safe in patients with MS over the age of 60. The side effects developed in this age group have similar profile to the side effects in young patients despite the comorbidities. None of our patients discontinue treatment due to adverse events. 53% of our patients did not show disease progression after the treatment and same number of patients showed stable disease radiologically after the treatment competition with no evidence of new and/or active lesions. We should braver treating our patients with MS in this age group as our review showed that DMT is relatively safe and effective.

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