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Future Treatments for RA



Stanley B. Cohen, MD: We know now that the JAK inhibitors—tyrosine kinase inhibitors—tofacitinib and baricitinib, which is under review by the FDA and approved by the European Medicines Agency—were both better than methotrexate in early rheumatoid arthritis, clinically and structurally. We know that other biologics, such as tocilizumab, ACTEMRA, were better than methotrexate in early disease.
The question will be, are there patients we should start these therapies instead of methotrexate, initially? Would the higher risk patient be better off in the long term, or does it really not make a difference? And, these data would suggest it doesn’t make a difference because you’ve got 6 months of grace and then you can start your therapy. So, I think that’s going to be a discussion that continues in the future. It’s really a cost-economic discussion, because the costs of these drugs are so expensive. If you can select out a third of patients who do just very well with methotrexate alone, you probably saved the healthcare system a tremendous amount of money.
The clinical trial data of this trial, and other trials like SWEFOT, support the guidelines for the professional societies, which suggest starting a conventional synthetic DMARD initially. And so, all of those guidelines are evidence-based, and based on studies of this nature. For now, the paradigm we’re using will be what we’ll continue with until we have future datasets suggesting that maybe we need to rethink it.
The good news is that there’s still a number of new therapies under development for rheumatoid arthritis. What we lack in rheumatoid arthritis, which are a critical deficiency, are treatment biomarkers. We lack a marker saying this patient is going to respond to TNF inhibition, or this patient is going to respond to T cell activation inhibition. We don’t have that. We’re very jealous of our oncology colleagues who are really way ahead of us in genetic testing and biomarker testing to tailor or personalize their therapy. Hopefully, we’ll get there. We spent a lot of money looking for treatment of biomarkers, but it has so far been unsuccessful.
There’s a lot of development continuing in looking at small molecules, which block signal transduction. We have the JAK inhibitors. There’s a lot of work on now looking at Bruton tyrosine inhibitors, BTK Inhibitors, which in theory make a lot of sense—blocking B-cell activation, androgen presentation, and so forth. I think we’re going to see more combination therapy again. We’re concerned about using combination therapy. We did that in the past with combination biologics and saw no added efficacy, even though animal models suggested that, but we saw more toxicity.
There is some scientific rationale in some of these small molecules blocking more than 1 signal transduction pathway. So, I think we’re going to see that with some of these antibodies that we call dual variable domain antibodies, where 1 Fab portion may block 1 cytokine and another may block another cytokine. I think combination therapy is coming. We need to be developing therapies for our treatment resistant patients, coming up with novel ideas, and willing to maybe accept more toxicity to try to lead to improvement in those patients.

 


Episode #1

Biologics for RA
Biologics for RA

Episode #2

Rheumatoid Arthritis Treatment Guidelines
Rheumatoid Arthritis Treatment Guidelines

Episode #3

Oral and Subcutaneous Methotrexate Use for RA
Oral and Subcutaneous Methotrexate Use for RA

Episode #4

TEAR Trial for Early Aggressive RA and Future Treatment
TEAR Trial for Early Aggressive RA and Future Treatment

Episode #5

RA Disease State Background and Clinical Burden
RA Disease State Background and Clinical Burden

Episode #6

Treatment Options for Rheumatoid Arthritis
Treatment Options for Rheumatoid Arthritis

Episode #7

Multidisciplinary Approach to Treating RA
Multidisciplinary Approach to Treating RA

Episode #8

TEAR Trial and Combination Therapy for RA
TEAR Trial and Combination Therapy for RA

Episode #9

RA Disease State Background
RA Disease State Background

Episode #10

Risk Factors and Clinical Burden for RA
Risk Factors and Clinical Burden for RA

Episode #11

RA Treatment Guidelines
RA Treatment Guidelines

Episode #12

Treating RA with Methotrexate
Treating RA with Methotrexate

Episode #13

Use of Biologics in Rheumatoid Arthritis
Use of Biologics in Rheumatoid Arthritis

Episode #14

TEAR Trial for Early Aggressive Rheumatoid Arthritis
TEAR Trial for Early Aggressive Rheumatoid Arthritis

Episode #15

Future Treatments for RA
Future Treatments for RA
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