MS Therapy Cladribine Remains Effective in Patients With Suboptimal Response to Prior Injectable DMT

Joshua Katz, MD

In the phase 4 CLICK-MS study (NCT03933215), treatment with cladribine (Mavenclad; EMD Serono) following suboptimal response to prior injectable disease-modifying therapy (iDMTs) led to low annualized relapse rates (ARR) among patients with relapsing multiple sclerosis (RMS). All told, this real-world study provided greater support for patients planning to switch to cladribine following inadequate treatment response with iDMTs.¹

The observational, single-arm study comprised 62 patients with RMS who switched from an iDMT to cladribine tablets. Of these, 34 (58%) completed the 24-month study period. Presented at the 2025 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, held May 28-31, in Phoenix, Arizona, results after 24 months revealed a low annualized relapse rate (ARR), at 0.02 (95% CI, 0.000-0.059), following the initiation of cladribine. Notably, at least 80.6% of patients with RMS (n = 50) remained relapse free over the 24-month period.

Led by Joshua Katz, MD, codirector of the Elliot Lewis Center for Multiple Sclerosis Care, the mean age of the sample was 49 years, with most patients female (79%) and White (83.9%). Coming into the study, the most common prior iDMTs were glatiramer acetate (56.5%) and interferon beta-1a (25.8%), followed by pegylated interferon beta-1a (6.5%) and interferon beta-1b (6.5%). Other DMTs included natalizumab (n = 3; 3.2%; patients were mistakenly enrolled into the study) and ofatumumab (n = 1; 1.6%).

Key secondary end points from the study included adherence and satisfaction as assessed by Multiple Sclerosis Treatment Adherence Questionnaire (MS-TAQ), and safety. Among MS-TAQ respondents, 30% (12 of 40) reported missing doses of injectable medication prior to cladribine; however, after the switch to cladribine, self-reported treatment adherence was high among respondents. Over the 2-year period, there was only 1 patient who missed or forgot to take their cladribine dose, which occurred in the second month of year 1.

READ MORE: Rebound Effect Not Observed With Multiple Sclerosis Therapy Ozanimod

In terms of treatment satisfaction, results on the MS-TAQ revealed that most felt it was “a little hard” to take injectable medication as recommended by their physician (MS-TAQ score: 2.1 [SD, 1.34]). In addition, on average, respondents (n = 40) were “a little satisfied” with their injectable medication (MS-TAQ score: 2.8 [SD, 1.32]). Following the switch to cladribine, respondents found it “extremely easy” to take the medication, and most were “very satisfied” with cladribine treatment.

Safety data showed that lymphopenia, COVID-19, herpes zoster, and urinary tract infection were the most common treatment-emergent adverse events (TEAEs), occurring in 14.5%, 8.1%, 6.5%, and 4.8% of patients, respectively. Over the 24-month period, 3 (4.8%) patients reported serious TEAEs. Of the 20 (32.3%) patients with RMS who discontinued cladribine, 3 (4.8%) discontinued because of lymphopenia. Despite the relatively high rate of discontinuations (45.2%), none were because of AEs.

At 24 months, grade 3 lymphopenia was reported in 1 (1.6%) patient, and no grade 4 lymphopenia was reported in patients who switched from iDMTs. Among those with available lymphopenia data (n = 21), 9 (14.5%) had normal absolute lymphocyte counts between 1000 to 4800, 6 (9.7%) had grade 1 lymphopenia (800 to <1000), and 5 (8.1%) had grade 2 lymphopenia.

Originally developed and approved in 1993 as an injectable treatment for certain leukemias under the name Leustatin, cladribine was later reformulated into an oral tablet for MS. It was finally approved in March 2019 as a treatment for adults with RMS, including relapsing-remitting MS and active secondary progressive MS. Cladribine is known for its short-course dosing regimen: patients take the medication for a maximum of 20 days over 2 years, with no additional treatment required in years 3 and 4. The medication still carries a boxed warning for potential risks, including malignancy and fetal harm, necessitating careful patient selection and monitoring.²

Click here for more CMSC 2025 coverage.

REFERENCES
1. Katz J, Pace R, Miravalle A, Aldridge J, Chandler A. DMT19 - Real-World Effectiveness and Safety of Cladribine Tablets in Patients with Relapsing Multiple Sclerosis after Suboptimal Response to Prior Injectable Therapy. Presented at: 2025 CMSC Annual Meeting; May 28-31; Phoenix, Arizona. Abstract DMT19.
2. Patient Labeling Review: Cladribine. FDA. March 19, 2019. Accessed May 29, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/022561Orig1s000OtherR.pdf