Does parenteral vs. oral glucocorticoid therapy influence steroid-free status in early RA?

Q. Can you explain the current recommendations for glucocorticoid use in early RA?

If we are looking at guidelines in early rheumatoid arthritis, the American College of Rheumatology (ACR) guidelines are actually different from the European Alliance of Associations for Rheumatology (EULAR) guidelines. I am an author on the EULAR guidelines, but the Canadians don’t follow everything perfectly. So the American College of Rheumatology says for inflammatory arthritis, that is RA or suspected RA, to start with appropriate therapy and to try to avoid glucocorticoids, because of the long-term risks. It is difficult to get patients off steroids and, in the long term, there’s risk of osteoporosis, diabetes, BMI issues, metabolic hyperlipidemia etc.

On the EULAR side of things, there are randomized controlled trials in active early RA, looking at high dose glucocorticoids with a taper over a couple of months with methotrexate and sulfasalazine, so the COBRA trial, COBRA-light, CareRA, various versions of that. There are multiple randomized controlled trials comparing treating early RA with the best standard of care (e.g., monotherapy combo or csDMARDs) versus the standard of care plus glucocorticoids – they do better, there’s less erosions and it changes the trajectory of joint damage, and more people go into remission and sustain remission.

EULAR also looked at a systematic review for formulating the guidelines in early RA, and they showed that although the idea was to bridge and get people off glucocorticoids, there is a percentage of patients stuck on chronic glucocorticoids. In some cases in standard of care, it might be 40% of patients that have very active disease, even 60% that would go into trials of advanced therapy, who are highly active and can’t get off of glucocorticoids. If you protocolize these patients, you can keep less than 25% on chronic glucocorticoids, so if you protocolize getting them off steroids, more people get off. There is also a confounding or a bias that the worst patients are often on steroids as well as another DMARD, not monotherapy steroids, but as an add on, which leads to our study.

Q. What were the objectives and design of this study in the CATCH cohort, and how was glucocorticoid use categorized?

The CATCH cohort is a Canadian arthritis cohort. It includes early proven or highly suspected RA patients who are within 1 year of their first fixed symptom of inflammatory arthritis, most of them were less than 6 months and the mean or median time was about 3 to 4 months from their first fixed symptoms. What we wanted to look at was patients that started with active disease, because we could enroll them when we treated them. So in the next visit, we could enroll them, so if the rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies were positive and we could see they had RA, when this wasn’t certain at the beginning.

We looked at active patients who were enrolled and looked over the next several months at what proportion were on glucocorticoids and how they were administered; orally compared to intra-articularly or intramuscularly. One way the patient can’t get the renewal, the other way they can. We looked at who would do better over 1 year, people never exposed, people ever exposed, a combination of intramuscular or intra-articular and oral, or chronic oral, and who could get off.

Q. What did the study find regarding oral versus parenteral glucocorticoids and outcomes at 12 months?

What we found at the end of 1 year was that the patients looked about equal. This was because patients who needed glucocorticoids to stay well were probably worse off, so it was hard to know, other than they started with higher disease activity or they didn’t fully respond to their initial treatment. There weren’t many patients on chronic glucocorticoids at the end of the year, but, in general, they needed those to look as good as the rest of the group.

What we found, which isn’t in the guidelines, was how to administer the glucocorticoids. If the physician or the practice controlled the steroids, i.e., via IM or IA or both, that less people would be on chronic glucocorticoids at the end of 1 year, because that would tide them over while their drugs started to work or while we changed their treatment. This is not randomized and there are prescribing biases, but based on this data, the recommendation I would say to peers is wherever possible, avoid oral steroids at 1 year. Oral steroids at 1 year could turn into 2 years, 3 years, 4 years, where you still can’t get patients off glucocorticoids and you run into side effects.

Q. How could these findings impact clinical decisions in managing early RA?

Again, this is observational and there is confounding, some sites use more oral glucocorticoids and some use more parenteral (intra-articular/intramuscular), but findings indicate that if a patient needs joint injections or needs glucocorticoid for high disease activity, that giving parenterally can get them into a better state without that risk of needing long-term steroids.

It also looks like if we can get people better faster, then they are less likely to need advanced therapies. So patients who never received steroids needed less advanced therapies at 1 year, and this is probably because their disease was milder or their drugs worked effectively early on. If they needed steroids intra-articularly or intramuscularly, they were less apt at the end of 1 year to require an advanced therapy. My translation to others in clinical practice would be, if possible, treat your patient highly effectively early. You might need to use glucocorticoids, but if you can limit this to intramuscular or intra-articular, then they might not be as long term as when using oral. This is an inference from the data, it is not an RCT to tell you which one is better, that IA/IM do as well as oral glucocorticoids, but seem to not be required as long term.