Objective:

To evaluate whether body weight > 110 kg influences lymphodepletion and recovery dynamics in multiple sclerosis (MS) patients treated with cladribine.

Background:

MS is a chronic demyelinating disorder of the central nervous system resulting in progressive disability through neuroinflammation and neurodegeneration. Among the over 20 FDA-approved disease-modifying therapies (DMTs), oral cladribine is the only agent with a weight-based dosing regimen. However, beyond 110 kg, dosing is fixed and no longer scaled to weight. To date, no study has evaluated the lymphocyte dynamics of patients weighing > 110 kg. Concerns for attenuated responses at weights above the scaled dosing range have led to clinical apprehension for prescribing cladribine, thereby limiting the accessibility of this DMT.

Design/Methods:

A retrospective chart review was performed on MS patients treated with cladribine at Froedtert and the Medical College of Wisconsin from March 2019 to May 2025. Inclusion criteria consisted of completion of the full treatment cycle, body weight ≥ 40 kg, and a baseline lymphocyte count ≥ 1000 cells/μL. Lymphocyte counts were collected at baseline and months 2, 11, 14, and 18 following drug exposure. Counts were analyzed using linear mixed-effects models through the lmerTest package in RStudio.

Results:

A total of 162 MS patients treated with cladribine were included in the analysis (122 female, mean age = 43.9 ± 9.4 years, mean weight = 81.3 kg (≤ 110 kg group); 131.0 kg (> 110 kg group)). There were no statistically significant differences between groups (p = 0.274). Pairwise contrasts at individual timepoints were similarly not significant.

Conclusions:

Lymphocyte dynamics were comparable between weight groups, indicating that cladribine’s capped dosing strategy remains effective at higher body weights. This finding supports the use of cladribine in patients weighing over 110 kg, thereby expanding confidence in prescribing cladribine to a broader patient population.