Combination Regimens to Treat Rheumatoid Arthritis
JUNE 18, 2020
Madelaine A. Feldman, MD: There have been studies in the past combining biologics, and the adverse effects and infections and problems that occur definitely do not outweigh any added benefit that they may have. Consequently, at this point, we are not combining biologics. Nor are we combining them with the JAK inhibitors. One of the issues that we see with the JAK inhibitors, perhaps a little bit more than with some of the biologics, is that there is an increased risk of shingles. Consequently, we really do not want to increase any infectious complications, so we do not combine the biologics. Nor do we combine them with the JAK/STAT inhibitors at this time.
There have been studies like the one I mentioned with tocilizumab regarding how the use of methotrexate did not give any added benefit in terms of the clinical response with tocilizumab. Certolizumab can also be used without methotrexate, as I stated, in cases of pregnant women. We have a large number of studies whose results show that it works quite well without methotrexate.
If this patient had some contraindications to increasing his methotrexate—for example, his liver functions continued to be elevated, or he had an alcohol problem that could not be controlled, or perhaps he was experiencing some other type of adverse effect or rash that he was having with methotrexate—we want to make sure that he is taking folic acid with methotrexate. The patient may be getting mouth ulcers, and that could be mitigated with the use of increasing folic acid. And sometimes we even add methylfolate, the activated folic acid. That can help us if we’re having problems increasing the amount of methotrexate. If we have to take the patient off methotrexate, then 1 of those 2 drugs, either the certolizumab or tocilizumab, would be a good choice.
Occasionally, we will use a different disease-modifying agent in conjunction, such as leflunomide. And occasionally, we will use Plaquenil [hydroxychloroquine] as an additive. Plaquenil is a very safe medication and often can give a little bit of an additive. As long as we’re not combining 2 biologics or a JAK inhibitor with a biologic, we sometimes see an advantage to having multiple medications on board.
All the while, this patient may still be on a low dose of prednisone. The idea is we want to get this patient to, at the very least, low disease activity and, if possible, to a state of remission. Now, a cure would be remission off medications. We’d like to get to that point, but we’re not there yet. Certainly, we’d like to take the patient off prednisone. So we could try one of the drugs that I had spoken about, and if there’s a problem with methotrexate, we could certainly use certolizumab. Or there’s tocilizumab. Then we should follow the patients again. Generally, we like to give it about 3 months. If the patient has not improved or has not gotten to a low disease state with the treat-to-target approach, we need to add on therapy, increase the dose, or change to a new medication.
Regarding the efficacy, in terms of the usual [American College of Rheumatology (ACR)] ACR20, ACR50, and ACR70 scores, we tend to see a similar type of response among most of the biologics. The ACR20s are usually in the 60% to 70% range. The ACR50s are somewhere in the 30% to 40% range. The ACR70s are in the 20% range, although sometimes we can get as high as 30%. With most of the TNFs [tumor necrosis factors], when methotrexate is added, we do see an increase in benefit in those ACR20, ACR50, and ACR70 scores. That is why we tend to use the methotrexate. It does tend to enhance the results and the ACR scores and get patients to more of a low disease activity.
Transcript Edited for Clarity