Tapering Treatment For Lupus Save

Hi, everyone. I'm Andrea Fava. I'm a physician and scientist from Johns Hopkins, connecting here from Euler in beautiful Vienna. And I wanted to give my thoughts about tapering of immunosuppression in lupus. There's been a lot of research going on in the last few years, new clinical trials, always trying to use less treatment or at least less steroids.

And this year there has been, this has been reflected in many sessions. In particular, was one focused on how to taper or withdraw treatment in rheumatic diseases. And I wanted to focus on the talks that focused on lupus. The first one was from Marie Horowitz from Canada, and they wanted to tackle the idea on how to taper that last five milligrams of prednisone in patients with lupus who are in remission. And they started from a previous experience from a Toronto cohort, the cortical loop trial, in which patients who were on remission but were still on five o prednisone basically had the prednisone withdrawn, and the experience was not good because after one year, twenty seven percent of the patient had a flare as compared to seven percent of the patient who remained on prednisone.

And so they took a different approach and they elaborated this taper regimen by which patients had to taper prednisone by on average one milligram every seven weeks, and they had more than 100 patients per group, they were randomized and propensity matched. And it was quite interesting to see the results because the surprise was that the patients at one ear who flared more were the patients who remained on prednisone five, and so they were like twenty nine percent of flares in the patient who remained on prednisone versus seventeen, and at twenty four months it was pretty much the same with just a higher number. What was interesting to see is that the damage accrual as expected was much higher in the group that remained on prednisone with a seventeen percent of total damage accrual versus six point nine patients that increased their damage. And the damage accrual was both from prednisone and also non steroid independent. The reason for this higher FLAIR, it's unclear, but it's definitely an interesting one.

The second session I wanted to comment on is about the tapering of immunosuppression in patients with lupus nephritis, and this was presented by Doctor. Panagiotopoulos, and they enrolled one hundred and thirty seven patients that were induced for lupus nephritis, and they were mostly on mycophenolate maintenance, and after a median of about three years, they decided to taper, actually withdrawn mycophenolate, and they looked over time at people who flared and looked for predictors of flares. And what they found is that being non responders in terms of lupus nephritis at one year was associated with a higher risk of flares, and instead having an early response was protective for not having a flare upon removal of mycophenolate. Having higher prednisone use at 12 was associated with more flares, whereas being on hydroxychloroquine was protected by cutting in half the risk of having flares. Having classified lupus nephritis had less risk of flares, but I think that the striking finding here is that sure, we want to taper immunosuppression, we want to sometimes take this little risk, but this risk comes at a price because in fact, the patients who flared had a significant increase in the risk of losing GFR permanently with a GFR drop of more than 30% all the way to end stage kidney disease and death, with a rate that was quite high.

So there were fifty three percent of patients who had one of these adverse outcomes among those who flared, who taper mycophenolate versus sixteen. So quite high. So we really need to find a strategy on how to best decide who are the patients in whom we could safely taper immunosuppression and not just hanging it because it comes at a permanent risk for patients. And of course there are studies that have been described in this meeting, such as the ReBioLoop studies led by Ioannis Porodis and Fred Lucio in which they are looking at the value of per protocol repeat biopsies after one year of treatment to decide eventually how, and understand how we could use this information to taper. And of course there are big proponents of doing repeat biopsies to do so.

And of course, I'm biased, but I think that the answer will come from non invasive biomarkers, which will help us eventually to decide who we can taper. And the very last comment I want to make is again on prednisone use, not so much about tapering, but a comment, it was a study was highlighted in the plenary on the first day by Lauren Arnaud, and there was a plenary on what's on the horizon for lupus. And he highlighted a study from Ali Duarte's group at Mayo in which they did a meta regression on several lupus nephritis studies and looked at the effect of high IV steroid pulses on the rate of response in lupus nephritis, and what they found that patients who received IV pulses had higher rates of response without significantly increased toxicity. So this is giving us a sense that perhaps hitting hard at the beginning, it's a better strategy that will allow us to use less prednisone later on and therefore avoiding damage, which resonates on the approach that we often have in some of these bad flares. Anyway, very interesting studies, interesting comments heard here at Hewler.

And for more information, you can go on RheumNow on the website. Thank you.