Real world experience with cladribine tablets for multiple sclerosis at four academic multiple sclerosis centers

Background: Cladribine tablets (CladT) are a multiple sclerosis (MS) disease-modifying therapy (DMT) with safety and efficacy established in the CLARITY trial and extension. A better understanding of the role of CladT in real-world populations is needed, including the clinical and radiographic trajectories of persons with MS (PwMS) treated with CladT and how CladT compares to other MS DMTs.

Methods: PwMS receiving CladT at 4 tertiary MS centers were identified and characterized. A validated electronic neuroperformance test adapted from the Multiple Sclerosis Functional Composite was administered at each visit, which provides z-scores for the Walking Speed Test (zWST), Manual Dexterity Test (zMDT), and the Processing Speed Test (zPST). The Patient Determined Disease Steps (PDDS) and NeuroQoL patient-reported outcomes are also administered. Regression modeling using generalized estimating equations was used to compare neuroperformance testing and brain MRI metrics at 6-, 12-, 18-, and 24-months to baseline. In a comparative effectiveness analysis, PwMS receiving other DMTs were propensity matched to CladT treated PwMS on variables including age, race, and disease duration. Outcomes were then compared at the same time points.

Results: We identified 117 PwMS treated with CladT who had an average age of 46.7 years (SD=10.5) and average disease duration of 13.2 years (SD=5.6). Relative to baseline, there were no significant differences in zMDT and zPST at any time point. There were significant increases in zWST over the study duration, suggesting improvement in walking speed, and PDDS scores remained stable during the study period. The odds of new T2 lesions relative to baseline were lower at all time points, but this did not reach significance. There were significantly lower odds of gadolinium enhancing (GdE) lesions at 6- and 18- months relative to baseline. Twelve PwMS (11 %) started a post-CladT DMT. We matched 476 PwMS on alternative DMT (most commonly ocrelizumab, n=280, 58.8 %) to CladT-treated PwMS. zWST scores were significantly better among those receiving other CladT at 12-, 18-, and 24 months, and NeuroQoL fatigue scores also favored the CladT-treated group. Odds of new T2 and GdE lesions were higher among those receiving CladT initially, but the disparity was no longer evident at 24-months (p=0.77 and p=0.55 respectively).

Conclusion: Real-world data for PwMS receiving CladT suggest it is prescribed to older patients with longer disease durations than in the pivotal trials. The pre-post analysis and the comparative effectiveness analysis suggested good performance of CladT in this broader population. There may be a delayed effect of CladT on radiographic outcomes relative to other DMTs.