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New TINIBs versus New MABs

Dr. Boulos Haraoui  Featured
June 12 2015 9:27 AM ET via RheumReports RheumReports

The battle used to be among the MABs or between MABs and CEPTs. Since there are no new CEPTs, the battle has shifted to a different front.

On the TINIB (tyrosine kinase inhibitor) side, there are promising data for baricitinib, a JAK1/2 inhibitor that is administered once a day. Two phase 3 studies were presented at EULAR 2015, in DMARD-IR and biologics-IR patients. Efficacy was similar to TOFA or the anti-TNFs. It seems that a dose of 2 mg is sufficient in DMARD-IR patients, but 4 mg was superior in biologics-IR patients. The safety data looked surprisingly good, especially regarding serious infections. However, there was an increased incidence of herpes zoster infections raising again the issue of immunizing all RA patients older than 50? or 60? or at least those starting a biologic agent or a TINIB. There were new safety issues with the TINIBs which will require monitoring, including a slight reduction of hemoglobin (due to inhibition of JAK2) and slight elevation of creatinine (unknown mechanism) meaning baricitinib should be used with caution (i.e., monitoring and dose reduction) in patients with impaired renal function.

On the MAB side, negative data were presented for two inhibitors of IL-23, ustekinumab (IL-12/23 ihibitor) and guselkumab (IL-23 specific inhibitor) raising some interesting lessons regarding the different operational pathways between RA and the SpAs.

New confirmatory positive data for mavrilimumab (anti GM-CSF receptor) were presented (Earth Explorer Study 1). No major respiratory side effects were reported which is interesting given the positive role of GM-CSF in activating pulmonary macrophages that clear surfactant.

If you thought that we were already confused and still learning how and when to use the more than 10 biologic / small molecule agents currently available, there are many more to come. Stay tuned.

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About the Author

Dr. Boulos Haraoui
Dr. Boulos Haraoui

Dr. Boulos Haraoui is an Associate Professor of Medicine at the Université de Montréal and head of the Clinical Research Unit. His research interests focus on the diagnosis and management of rheumatoid arthritis.

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