Comparing the Infectious and Neoplastic Adverse Event Profiles of Ocrelizumab and Cladribine Using the FDA Adverse Event Reporting Database
Nasrin Rahimian1, Olaf Stuve2, Afsaneh Shirani3
1Department of Neurology, Creighton University Medical Center, Omaha, Nebraska, 2Department of Neurology, University of Texas Southwestern Medical Center and Dallas VA Medical Center, Dallas, Texas, 3Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, Nebraska
Objective:
To investigate the infectious and neoplastic adverse event (AE) profiles of ocrelizumab and cladribine for treatment of multiple sclerosis (MS) using the Food and Drug Administration Adverse Event Reporting System (FAERS) database.
Background:
Ocrelizumab, an anti-CD20 monoclonal antibody, and cladribine, a purine nucleoside analog, are both considered high-efficacy disease modifying therapies for treating relapsing forms of MS. Their real-world safety profile, however, has not been adequately compared.
Design/Methods:
We performed a disproportionality analysis of the FAERS database between the first quarter of 2004 and the second quarter of 2023 using the OpenVigil2.1-MedDRA software. Preferred terms for common infectious and neoplastic AEs were extracted using MedDRA v.26. A signal was detected if the number of drug–AE reports was ≥3 and the proportional reporting ratio was ≥2 associated with a χ2 value of ≥4.
Results:
There were a total of 7,522 and 2,561 AE reports for ocrelizumab and cladribine, respectively. Among the most relevant infectious AEs, signals were detected for ocrelizumab for upper respiratory tract infections (URTI) (ROR [reporting odds ratio]:2.36; 95%CI:1.787-3.135), pneumonia (ROR:2.821; 95%CI:2.297-3.465), COVID-19 (ROR:31.889; 95%CI: 29.155-34.881), urinary tract infection (UTI) (ROR:2.055; 95%CI:1.846-2.289), and herpes virus infection (ROR:7.476; 95%CI:4.738-11.795). Similar analyses for cladribine detected signals for URTI (ROR:2.143; 95%CI:1.307-3.515), pneumonia (ROR:2.098; 95%CI:1.824-2.412), and COVID-19 (ROR:3.82; 95%CI:2.886-5.056), but not for UTI and herpes virus infection. No neoplastic safety signals were detected for ocrelizumab or cladribine regarding breast cancer, ovarian cancer, malignant melanoma, squamous cell or basal cell carcinoma, lung cancer and pancreatic cancer.
Conclusions:
This study showed differences in infectious AEs between cladribine and ocrelizumab, with infections appearing to be more frequently associated with ocrelizumab. However, no differences in neoplastic AE signals were noted. Overall, cladribine was not found to have a worse AE profile compared to ocrelizumab. Further longitudinal studies are needed to rigorously compare the real-world AE profile of ocrelizumab and cladribine.