Janet Pope, MD, MPH: Treating Unresponsive Rheumatoid Arthritis

Rheumatology Network interviewed Janet Pope, MD, MPH, to delve into her recent Congress of Clinical Rheumatology (CCR) East presentations, “Treatment Strategies for the Unresponsive Patient with Rheumatoid Arthritis” and “2021 Year in Review: Clinical Pearls.” Pope is Professor of Medicine and Division Head of Rheumatology at Western University in London, Canada.

Rheumatology Network: What are some of the treatment strategies that you suggest for patients with rheumatoid arthritis (RA) who are unresponsive to their current medication?

Janet Pope, MD, MPH: In rheumatoid arthritis, roughly 1/6 to 1/3 of patients are considered difficult to treat. This could mean that the drugs stopped working, never worked, the patient does not tolerate them, or there's contraindications to them. So, in this pool of patients, which isn't too uncommon, we go through an algorithm based on guidelines. The American College of Rheumatology (ACR), for instance, has guidelines. And basically, we try to continue to treat the patient to get them into remission or low disease activity, because that gives better quality of life and less joint damage down the road. The algorithms we tend to use are our conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) like methotrexate, and in Canada, we use other csDMARDs and combine them. In the US, it would often be adding a different drug, such as a biologic disease-modifying antirheumatic drug (bDMARD) like a tumor necrosis factor (TNF) inhibitor, or possibly an oral JAK inhibitor.

After that, we really don't know what to do next. We usually go out of class to something else, but we don't know, in any one patient, what will be their home run drug. And even if we find a home run drug, it might not last forever. So that's sort of the dilemma in these difficult-to-treat patients. It is evidence based, but we also fly by the seat of our pants.

I asked rheumatologists at the CCR what they would do next. The options were split and there was no consensus, and they were all right answers potentially. We need research that will help us to define what will be the next best treatment. In rheumatology, for RA treatment, we have lots of options. But as I say, we don't know what one will be the best for benefit and tolerability and for the longest amount of time. By the data, it’s probably better to go out of the TNF class to something else to get a deeper and longer response on the average patient.

The other thing is to not give up trying work with your patient and trying to see what's driving the difficulty. Are they not taking it because they don't tolerate it? Can they afford it? Are they afraid because their friend told them there might be issues with the drug? We also must look at the reasons why someone might be difficult-to-treat that isn't necessarily related to the drug but related to taking the drug and the fear or the access tissues.

RN: Your second presentation focuses on the clinical pearls from the last year. What are some of your favorite developments that you discussed?

JP: One thing that's really interesting is there are a lot of trials that have gone on with gout involving treating to a target and what we know about gout. For example, common risk factors of crystal arthritis are age, poor kidneys, alcohol, and diuretics. It's very common that people living with gout, if we target the uric acids to try to lower it, you don't have to target it too low. You get no added benefit coupled with more potential drug changes and side effects. So, targeting to a normal level is good enough.

We also know that uric acid itself is a risk factor for heart attack. It’s independent risk factor for coronary artery disease. They've looked at studies on treating asymptomatic uric acid, which have yielded mixed results; some indicate it decreases cardiovascular risk, but some don’t.

There were also a lot of trials last year in osteoarthritis where drugs or injections weren't successful. Some drugs that might be disease-modifying have, in the long run, not proven to be of any greater benefit than our standard of care and have potential neuropathy or nerve toxicity side effects. So, they're not going to be developed further, as far as I can tell, unfortunately.

There's also a lot of news about injecting platelet-rich plasma, stem cells, and other expensive products into joints. And, in general, the benefit is not there when you compare it to a standard of care in randomized controlled trials. I'm not saying that in all cases it's non-beneficial, but in general, platelet-rich plasma is not going to help your knee osteoarthritis. It might help elbow tendonitis, but that's not as common as knee osteoarthritis.

Some of it has to do with trial design, but when new results come out, we're enthusiastic and then over time, we have to ask ourselves if these products are actually going to be effective for our patients or not.