Post-partum relapses after alemtuzumab

One of the problems of immune reconstitution therapies (IRTs), such as HSCT, alemtuzumab and cladribine, is nagging worry that at some time in the future your MS will reactivate. Some people with MS (pwMS) try and avoid potential triggers of disease activity, for example, vaccinations and pregnancy, particularly the post-partum state. Unfortunately, there is some evidence the latter may trigger disease activity, but at quite a low rate. 

The following is the data on 122 pregnancies post-alemtuzumab presented earlier this year at ECTRIMS. The annualised relapse rate (ARR) fell to 0.02 during pregnancy, i.e. 2 relapses in 100 years, with 98% of patients being relapse-free. In comparison, in the first year after pregnancy, the ARR was 0.22, i.e. 22 relapses in 100 years of follow-up, with 82% of patients being free of relapse. The ARR was then similar to pre-pregnancy levels in the second and third years after pregnancy (0.12 each year; with 89% and 92% of patients relapse-free in each year, respectively).

One of the reasons for women with MS choosing an IRT is to start or extend their families. Based on this data I would recommend that they do just that and in the unlikely event of post-partum disease activity (1 in 5 chance) it can be dealt with by an additional course of treatment or possibly starting another DMT. What do you think?

We have many patients in our centre who have had children after alemtuzumab in our centre. I refer to them as the alemtuzumab babies because they represent the success of treating MS early and effectively. It was only 20 years ago that the previous generation of neurologists were advising their patients with MS not to have children. How times have changed?

Celius et al.  Postpartum relapse after first on-study pregnancy in RRMS patients treated with alemtuzumab in the phase 2 and 3 clinical development program over 8 years. ECTRIMS Online Library. Celius E. Sep 12, 2019; 279136; P776

Introduction: In childbearing women with MS, relapses may increase in frequency and severity during the postpartum period. In phase 2 and 3 clinical trials of alemtuzumab (CAMMS223 [NCT00050778]; CARE-MS I [NCT00530348]; CARE-MS II [NCT00548405]) and their extensions (CAMMS03409 [NCT00930553]; TOPAZ [NCT02255656]), alemtuzumab significantly reduced relapse rates in RRMS patients versus SC IFNB-1a and maintained efficacy over 8 years. Product labelling recommends use of contraception in women of childbearing potential for 4 months after treatment.

Aims: To examine over 8 years relapse rates before, during, and after the first pregnancy in alemtuzumab-treated patients in the CARE-MS and extension trials.

Methods: Contraceptive use was required during core studies, and for 6 months after alemtuzumab administration in the extension studies. The analysis included patients who received alemtuzumab (baseline: 5 days; 12 months later: 3 days) in phase 2 or phase 3 trials or their extension studies and became pregnant after receiving at least one dose of alemtuzumab. Patients could receive other DMT or additional as-needed alemtuzumab (12 mg/day on 3 days; ≥12 months apart) in the extensions. After pregnancy, other DMT was allowed in CAMMS03409; other DMT or further alemtuzumab was allowed in TOPAZ. The analysis only considered a patient’s first pregnancy, regardless of the outcome. Pregnancy had to occur by Month 85 to allow for at least 1-year follow-up post-pregnancy onset.

Results: Over 8 years, 122 pregnancies met inclusion criteria; 72% of pregnancies began >12 months after the last alemtuzumab dose, 18% began >4 to 12 months after the last dose, and 10% began ≤4 months after the last dose. Annualised relapse rate (ARR) in the year prior to study entry was 1.8. Two years and 1 year before pregnancy, ARR was 0.10 and 0.12 respectively, with 91% and 89% of patients free of relapse. ARR fell to 0.02 during pregnancy (98% of patients relapse-free). In the first year after pregnancy, ARR was 0.22, and 82% of patients were free of relapse. ARR was similar to pre-pregnancy levels in the second and third years after pregnancy (0.12 each year; 89% and 92% of patients relapse-free in each year). Safety will be discussed in the presentation.

Conclusion: In the year after the first pregnancy in alemtuzumab-treated patients, an increase in relapse rates was minimal and less than that expected from the literature. Relapse rates returned to pre-pregnancy levels by the second year postpartum.

CoI: multiple