RIP to Glucocorticoids in GPA Save

For many years glucocorticoids were the mainstay of our treatment of granulomatosis with polyangiitis (GPA). The paradigm shifted with cyclophosphamide and then again with rituximab, and we used less steroids, but we still used lots. Avacopan teased the demise of steroids, but in the trial they, and now we, still use them. Glucocorticoids are our old trusty friend, our comfort blanket. But no more! Good riddance to the medication with the highest long-term adverse event burden that we use. Long-term glucocorticoids in GPA should now be a rarity.

The reason for such exuberance is the study presented by Dr. Peter Merkel at Saturday’s opening plenary session, Abstract 0774. This is the TAPIR study, the results of which I feel like I have been eagerly awaiting for years. I know some will be thinking “who cares about 5mg prednisone, give it or don’t give it”. The data does not support this attitude. Yes 5mg is far better than 60mg or 20mg, but it is still associated with meaningful long term adverse effects on bone, cardiovascular risk, and infection. It is a clinical question that arises every day for me. People with GPA want to stop their glucocorticoids and now we have the evidence to endorse this.

So what did TAPIR show?

In 143 GPA patients in remission, prednisone 5mg was stopped or continued. The primary endpoint was relapse at 6 months. First finding was that relapse was low in either group, 16% vs 4%. Now in terms of relative risk that is an appreciable odds ratio of 4.22, but the absolute risk is small in either group. 93% of relapses were minor, with only 1 serious relapse during the trial.

Things got really interesting though when they parsed out the patients who received rituximab as part of their treatment. In that subgroup, there was no significant difference in relapse – 9% vs 6%. That’s important as nearly all the patients I treat get rituximab. I don’t know who these people not getting rituximab were, but when I think of a GPA patient, rituximab is standard of care.

This is absolutely game-changing for me. Previously I generally recommended continuing glucocorticoids. Now I can have an informed discussion with the person living with GPA, have figures to support that discussion, and reach a shared decision. I know I’ll be pushing to consign the glucocorticoids to the bin.