Vasileios-Periklis Stamatellos1, Antigony Rigas2, Eleni Stamoula3, Aimilios Lallas4, Athina Papadopoulou5, Georgios Papazisis6. 1. Department of Clinical Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece; Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research and Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland. 2. School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece. 3. Department of Clinical Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece. 4. 1st Department of Dermatology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece. 5. Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research and Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland. 6. Department of Clinical Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece; Clinical Trials Unit, Special Unit for Biomedical Research and Education, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece. Electronic address: papazisg@auth.gr.
Abstract
INTRODUCTION: S1P receptor modulators are oral Disease-Modifying Therapies (DMTs) for Multiple Sclerosis, which were associated with cases of basal cell carcinoma in clinical trials. This study aims at investigating in a real-world adverse event reporting system whether S1P receptor modulators increase the risk of skin cancer reporting, compared to other DMTs. METHODS: Adverse event reports from the FDA Adverse Event Reporting System (FAERS) were extracted, cleaned, and analyzed from 2004Q1 until 2020Q4. The crude and adjusted Reported Odds Ratios (cROR, aROR) for the outcomes: basal cell carcinoma, squamous cell carcinoma, or melanoma were calculated for all DMTs. In a sensitivity analysis, we looked at each outcome separately. RESULTS: The aROR (95%CI) of siponimod was: 9.68 (5.48-15.79) and of fingolimod 4.54 (3.86-5.32), indicating a safety signal of S1P receptor modulators for skin cancer. Ozanimod had only 52 complete reports without any cases. In the sensitivity analysis, siponimod showed a signal only for basal cell carcinoma: 22.83 (12.27-38.83), while fingolimod for all outcomes separately, including melanoma: 3.02 (2.31-3.89). Notably, among the other DMTs, alemtuzumab: 4.40 (2.98-6.25) and cladribine: 3.28 (1.17-7.13) presented also a signal for disproportionate reporting, while ocrelizumab showed a signal in the sensitivity analysis only for melanoma 2.55 (1.21-4.65). CONCLUSIONS: S1P receptors seem to increase skin cancer reporting on FAERS, and the association is strongest for basal cell carcinomas. Therefore, close dermatologic surveillance before- and during therapy is needed. Whether fingolimod and ocrelizumab also increase the risk of melanoma needs further investigation.
INTRODUCTION: S1P receptor modulators are oral Disease-Modifying Therapies (DMTs) for Multiple Sclerosis, which were associated with cases of basal cell carcinoma in clinical trials. This study aims at investigating in a real-world adverse event reporting system whether S1P receptor modulators increase the risk of skin cancer reporting, compared to other DMTs. METHODS: Adverse event reports from the FDA Adverse Event Reporting System (FAERS) were extracted, cleaned, and analyzed from 2004Q1 until 2020Q4. The crude and adjusted Reported Odds Ratios (cROR, aROR) for the outcomes: basal cell carcinoma, squamous cell carcinoma, or melanoma were calculated for all DMTs. In a sensitivity analysis, we looked at each outcome separately. RESULTS: The aROR (95%CI) of siponimod was: 9.68 (5.48-15.79) and of fingolimod 4.54 (3.86-5.32), indicating a safety signal of S1P receptor modulators for skin cancer. Ozanimod had only 52 complete reports without any cases. In the sensitivity analysis, siponimod showed a signal only for basal cell carcinoma: 22.83 (12.27-38.83), while fingolimod for all outcomes separately, including melanoma: 3.02 (2.31-3.89). Notably, among the other DMTs, alemtuzumab: 4.40 (2.98-6.25) and cladribine: 3.28 (1.17-7.13) presented also a signal for disproportionate reporting, while ocrelizumab showed a signal in the sensitivity analysis only for melanoma 2.55 (1.21-4.65). CONCLUSIONS: S1P receptors seem to increase skin cancer reporting on FAERS, and the association is strongest for basal cell carcinomas. Therefore, close dermatologic surveillance before- and during therapy is needed. Whether fingolimod and ocrelizumab also increase the risk of melanoma needs further investigation.
Authors: Bruce Ac Cree; Krzysztof W Selmaj; Lawrence Steinman; Giancarlo Comi; Amit Bar-Or; Douglas L Arnold; Hans-Peter Hartung; Xavier Montalbán; Eva K Havrdová; James K Sheffield; Neil Minton; Chun-Yen Cheng; Diego Silva; Ludwig Kappos; Jeffrey A Cohen Journal: Mult Scler Date: 2022-06-28 Impact factor: 5.855