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Master Thesis

Liens entre cancers cutanés et traitements anti-JAK : revue des données actuelles de la littérature et analyse du profil des cas rapportés à partir des données de la base mondiale de pharmacovigilance

Abstract : Skin cancers represent a major public health issue and share some common risk factors such as UV radiation or immunosuppression. Among the new immunomodulatory medicines, JAK inhibitors are a recent molecule class which will be increasingly prescribed for many dysimmune diseases. The aim of our study is to determine whether the JAK inhibitors currently available on the market (ruxolitinib, tofacitinib et baricitinib) are associated with an increased risk of skin cancers. In the first part, our literature review has found a moderate increase in skin cancers in the phase 3 studies with ruxolitinib, and an absence of apparent risk in the available meta-analysis for tofacitinib and baricitinib. In the second part, we searched the global pharmacovigilance database for signals of disproportionality between JAK inhibitors and skin cancers, and analysed the profile of reported cases. The present study identified 870 individual case safety reports between 1978 and 31.12.2019 in Vigibase, associating JAK inhibitors and melanoma, squamous cell carcinoma or Merkel carcinoma. Disproportionality signals were detected for all of the skin cancers with ruxolitinib and tofacitinib, and were found significantly elevated for Merkel carcinomas alone in the case of baricitinib. These results support a possible class effect between the occurrence of skin cancers and JAK inhibitors, especially as the source population of patients is not the same according to the molecule studied (rheumatoid polyarthritis in the case of ruxolitinib and myelodysplasia for the tofacitinib and baricitinib). We also draw attention to the case of Merkel carcinoma, rare tumours favoured by immunosuppression which are notably over-represented in our sample. The hypothesis of a favourable effect of JAK inhibitors on its carcinogenesis by interaction with anti-tumour immunovigilance and antiviral response could thus be raised. However, these results only suggest, and not affirm, a causal link between skin cancers and JAK inhibitors, due to the inherent limitations of the detection of pharmacovigilance signals. Moreover, the existence of potential confounding biases, such as the prior intake of skin cancer providers such as hydroxycarbamide, may disrupt the interpretation of our results. Our results should encourage continued reporting of skin cancers associated with JAK inhibitors in pharmacovigilance, and could be confirmed by pharmaco-epidemiology studies. Regular dermatological screening could be beneficial in vulnerable patients treated with JAK inhibitors to detect early onset of skin tumours.
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Master Thesis
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Submitted on : Thursday, October 1, 2020 - 9:57:54 AM
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Cédric Jalles. Liens entre cancers cutanés et traitements anti-JAK : revue des données actuelles de la littérature et analyse du profil des cas rapportés à partir des données de la base mondiale de pharmacovigilance. Médecine humaine et pathologie. 2020. ⟨dumas-02954457⟩

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