Jeffrey A. Sparks, MD, MMSc

JAK Inhibitor Selectivity and Dose-Related Toxicity

Video content above is prompted by the following:

Mechanism of action also differs in the Janus kinase (JAK) inhibitor class. Tofacitinib inhibits JAK1/JAK2/JAK3, baricitinib inhibits JAK1/JAK2, and upadacitinib inhibits JAK1. Can you describe how more specific selectivity of JAK inhibition influences dose-related toxicity? 

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Panelists discuss how the varying selectivity of JAK inhibitors—such as tofacitinib's broad inhibition of JAK1/JAK2/JAK3, baricitinib's inhibition of JAK1/JAK2, and upadacitinib's focus on JAK1—affects dose-related toxicity and overall treatment safety.

JAK Inhibitors vs TNF Inhibitors: Effects on Administration, Efficacy, and Safety 

Tumor necrosis factor inhibitors (TNFis) and Janus kinase inhibitors (JAKis) present with differing characteristics and mechanisms of action (MOA), both between the 2 classes and within each class.

Multiple characteristics distinguish JAKis from TNFis. For example, JAKis are stable small molecule proteins with a short half-life whereas TNFis are heat-sensitive monoclonal antibodies with a long half-life. How do their differences affect administration, efficacy, and safety outcomes?

The MOA within the TNFi class also varies. Etanercept binds both TNF-a and TNF-b with high affinity whereas infliximab, adalimumab, golimumab, and certolizumab-pegol bind to TNF-a with high affinity but not TNF-b. What implications are associated with these different binding activities

Panelists discuss how JAK inhibitors and TNF inhibitors differ in administration, efficacy, and safety due to their unique characteristics and mechanisms of action, with further variations in binding activities within the TNFi class impacting clinical outcomes.

Guiding Treatment Decisions: The Role of Remission Data and Head-to-Head Comparisons

How do head-to-head data affect your treatment decisions?

What does consistency of remission across patient types mean to you?

How often do you rely on remission data when considering switching therapies?

Panelists discuss how head-to-head clinical trial data shape their treatment decisions, the significance of consistent remission rates across different patient populations, and the frequency with which remission data influence their choices to switch therapies.

Advanced Treatment Options for RA: Exploring the Data

Let’s discuss data of advanced treatment options for rheumatoid arthritis (RA) that may offer a faster pathway to achieving remission.

Please discuss the SELECT-COMPARE trial head-to-head data on upadacitinib vs adalimumab. 

Please discuss the use of upadacitinib for active RA refractory to biologic disease-modifying antirheumatic drugs (SELECT-BEYOND trial).

What are the remission rates seen with upadacitinib vs abatacept (SELECT-CHOICE trial)?

Panelists discuss advanced treatment options for rheumatoid arthritis, focusing on the SELECT-COMPARE trial's head-to-head data of upadacitinib versus adalimumab, the use of upadacitinib in active RA refractory to biologics (SELECT-BEYOND trial), and the remission rates of upadacitinib compared to abatacept (SELECT-CHOICE trial).

Jeffrey A. Sparks, MD, MMSc

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