RheumNow Podcast – Enough Already With Weaning (6.19.20) Save

It's the 06/19/2020. This is the RheumNow podcast. Hi. I'm doctor Jack Cush, executive editor of rheumnow.com. This week, hydroxychloroquine's out, canakinumab is in, and tocilizumab is holding on for dear life in those who are holding on for dear life.

We're gonna start out with a reminder of last week's roundup and week review. We actually did a EULAR roundup, doctor Arty Cavanaugh and myself, a thirty minute recording where we won't go over about seven or eight of our favorite abstracts from EULAR two thousand twenty, a virtual meeting. I think it's a worthwhile listen, view, or even read if it's available as a read. We're gonna start off with a news item about ankylosing spondylitis. An interesting analysis in, I believe it's J Rheum, looked at a large cohort of over 10,000 ankylosing spondylitis patients and compared, African Americans with AS to those who were Caucasian and showed that African American patients to have AS had to have more anterior uveitis, more hypertension, diabetes, depression, heart disease, and higher sed rate and CRP levels.

So it's not surprising when you remove b twenty seven from the picture, you know, b twenty seven is only about fifty percent prevalent in African Americans compared to Caucasians where it's over ninety percent, that you may change the disease, but in removing the marker, maybe it's harder to make the diagnosis. It's harder to make the diagnosis, you have to have more bad features to get there, and so I think that's what's evident here, African Americans, and I can think of the ones I've seen, they tend to have worse disease. They tend to have I would expect it to have seen more, you know, fusion worsening, but I don't think that that was a measurable outcome in this study. Interesting nonetheless, there was a nice review of the, challenge of rheumatology workforce shortages for the future. As you know, we've been reminded by Chad Deal and the ACR workforce, team about our projections on shortages, and it's because we have a tsunami of older white haired rheumatologists who are about to retire, and we're gonna have a major shortfall in the years to come.

This article proposed several, measures to combat that. One, increase rheumatology train training program output. We need more programs. We need more fellows in our programs. It's not a fast change that one can make, but it certainly is a much needed change if we're to address the population need for musculoskeletal care in the future.

Second was to expand the use of and get more, nurse practitioners, physician assistants, and even pharmacists involved in the care of our patients. You know, one such example would be, you know, bring back the Gold Clinic. Gold Clinic was run by nurses who would take care of our patients and give them gold every week. That could happen for gout management, that could happen for treat to target RA management, where, an NPPA pharmacist, could actually be given protocols and manage those patients and unload a lot of the burden that's currently on rheumatologists. Third, telemedicine expansion.

Hello COVID, did this not happen in the last two months? Are not a multitude of you now proficient in televideo and telephone phone calls? I know that about a thousand of you have looked at my video on the virtual video joint exam. I think you can find that useful. In fact, I do the virtual, video joint exam when I'm in the room with the patients these days where there's six feet six feet between them and me.

I got my goggles on, my mask on, my gloves on. I can touch them and examine them. I just think it's better for everyone if I don't do it unless I have to. So I still do the same, you know, fist bump, prayer sign, hands on ears. The same thing I went over in the video.

Look at that. I think you'll find it. And lastly, we need to address the issue of physician burnout, a major problem, amongst all physicians, especially rheumatologists. And I think that that really I am not seeing major smart efforts to address that. So there was a tweet that we put out during ULAR about don't stop the TNF inhibitor and people who are on our who are in remission are with rheumatoid arthritis.

This is data from the Arctic Rewind study where there are two arms that study where they took patients who are on either a DMARD, a conventional synthetic DMARD like methotrexate or on a biologic like a TNF inhibitor, and they either stopped the biologic or stopped the the DMARD, and they didn't stop them. They half the dose, and if the patients who are in remission did well, they then stopped the therapy. Well, that study fairly convincingly showed that, again, patients who stopped their TNF inhibitor were gonna flare. Sixty three percent of them flared versus the five percent who didn't stop their TNF inhibitor. The same extent, but less with the stopping or or weaning the the the, DMAR therapies.

I don't know why we're still seeing these studies. I don't know why we're still talking about weaning or stopping therapy. You spend your whole life trying to manage a horribly complex disease with multiple therapies. You're successful and you're good at it, and and now we wanna have discussions about stopping therapy. It's foolish.

Now, know patients want to be on less drug, and you may want them to be on less drug, but there's a price to be had here when that happens. I actually did a Twitter poll during you, Lauren, I asked the question, in your RA patients who are in low disease activity or in remission, what do you do with their therapies? Do you maintain, reduce, or stop the DMARD? You said, thirty five percent said continue what works. Fifteen percent said the patient drives the equation.

And then you were split between twenty eight percent wanting to reduce the DMARD and twenty three percent who wanna reduce the biologic. I get the sentiment. I just don't think we need a lot of studies to prove what's already known here. If you stop therapy, there's a price to be paid. Another interesting abstract I didn't go over in any of the broadcasts, came from a French group that looked at the French registries for tocilizumab, rituximab, abetacept, and specifically looked at the incidence of GI perforations.

We know it's a risk factor with the IL-six inhibitors, we know it's a risk factor also with the JAK inhibitors. So in their very large cohort, they showed that gastrointestinal perforation was higher with tocilizumab compared to rituximab and abatacin. Not a surprise, been shown before. What they kinda showed was that that risk was linked more so to the risk of diverticulitis. So tocilizumab driving the risk of diverticulitis is what caused the GIP, gastrointestinal perforations.

As you know, work by Jeff Curtis and others have shown that steroids is the greatest risk factor for perforation. Steroids also cause diverticulitis. DMARDs, not so much. Other biologics, not so much. So is it really that these drugs cause more diverticulitis than outright GI perforations?

I don't think you can separate the two, but it's certainly interesting to think about that. Again, the rule here is be cautious about using an IL six inhibitor or a JAK inhibitor in people who have diverticulitis, but not worry about it in people who have diverticulosis. An interesting report this week from MMWR and the CDC says that COVID hospitalis hospitalizations were, six times higher and deaths were twelve times higher when a COVID patient had a comorbidity. So, what we've learned from our analyses of our patients is our patients are doing pretty good, our rates are pretty low. Our patients who are supposedly immunosuppressed, on immunosuppressants, they're not.

They're well controlled and they're on largely anti inflammatory therapies and they've done very well with a very low frequency of COVID events and COVID deaths. Is that because, well, they have comorbidities and the most common comorbidities that seem to be killer in COVID are people who have cardiovascular disease thirty percent, diabetes thirty percent, chronic lung disease eighteen percent, that's the data from the CDC. Those are the ones you worry about when they get hospitalized or they get the coronavirus infection. So congratulations to you who are managing your patients and doing so well, Worry about your patients who have comorbidities who may get infected. The FDA revoked its prior authorization for the use of hydroxychloroquine in patients with the COVID nineteen infection.

That emergency authorization use basically said it shouldn't be used by people as outpatients, it should be only used in people who are in clinical trials studying hydroxychloroquine or emergently, urgently in people who are hospitalized with COVID. So people who are doing prophylactic use, of hydroxychloroquine and people are stockpiling it, that's sort of idiotic. A lot of the negative reports on hydroxychloroquine and blame hydroxychloroquine when in fact, it's very sick patients with comorbidities who are dying, who just happen to be sick enough to get hydroxychloroquine. Nonetheless, the FDA has revoked its emergency use authorization for hydroxychloroquine. Those people who are in studies are gonna complete their studies, but right now, there's not a lot of enthusiasm for hydroxychloroquine in The US that has stockpiled something like, you know, forty million or billion doses of it are probably gonna have to eat the cost of it.

Good news is there shouldn't be a shortage of hydroxychloroquine going forward for you and your patients. A windfall this week for Novartis two FDA approvals on the same day. Canakinumab became the first ever FDA approved drug for use in adult onset Still's disease. As you know, canakinumab also known also called Ilaris is also approved for other periodic fever syndromes including CAPS and FMF and TRAPS patients in the hyper IgD syndrome. It was approved a few years ago for kids with systemic onset JIA.

And based on a report out of, I think Germany, that was a very small pilot trial, the FDA has actually licensed its use now for adult onset Still's disease. Number one, doing this basically is a regulatory decision to say that systemic onset JIA and adult onset JIA, adult Still's disease, are the same disease. This has been a major hurdle at the agencies about how to consider, studies in this area. So that's a windfall. Drug was actually approved based on a thirty six patient, adult patient trial where they say the safety profile and the efficacy outcomes were largely similar to that seen in systemic onset JIA.

Those studies that led to its approval were largely on articular outcomes and and not necessarily systemic outcomes, although systemic benefits are clearly seen when using IL-one inhibitor. So, again, what happened? The dosing here is, four milligrams per kilogram with a maximum up to three hundred milligrams as a single daily dose. And, again, you might need higher doses in patients who are very sick with systemic disease and systemic JIA. The doses that were used, for canakinumab were, given every four weeks.

So, recognize that higher doses and then given every four weeks is is probably reasonable. Again, the, other parameters here of safety, efficacy, and pharmacokinetics, I think were worked out in in a small adult population that led to its approval. The other approval was for secukinumab or Cosentyx in the treatment of non radiographic axial spond yloarthritis. This now becomes the third drug to be FDA approved for non radiographic axial spondyloarthritis. Say that three times fast, tell me how many patients you have with non radiographic axial spondyloarthritis.

I didn't think I had any until I started saying I didn't have any, then all of sudden I got a whole bunch of them. So I think this is a an advantage, I think, for those of you who no longer have to worry about how to get the drug approved if they don't yet have evidence of radiographic sacroiliitis. Non radiographic axial spondyloarthritis patients are patients who have normal SI X rays but either have inflammatory back pain with either a high CRP or an abnormal MR image of the SI joint. So, anyway, this is a a nice advantage. This particular approval is based on the Prevent study.

That was a 555 patient trial. I think it's a two year trial. The primary endpoint was at 52 where the ASAS 40 results were significantly higher in those on secukinumab compared to placebo. Again, this is the third drug, cerdulizumab, eixekizumab just two weeks ago was approved. Now this is the third drug that's approved.

I think we can now better better study and do research on these patients with these drug approvals. How should the drug be given? The two ways it was approved for was either with or without a loading dose of a hundred fifty milligrams subcutaneously on weeks zero, one, two, three, four, five doses given weekly, and then given every four weeks or just give it at week zero and then every four weeks. Both dosing regimens were FDA approved. There were no new safety signals when this particular novel cohort was given sacukinumab.

Lastly, we had a report today on, the mixed results with tocilizumab in COVID nineteen patients. I put this up because there's been a lot of rumblings about tocilizumab not doing well in a in a in a Italian study. And believe me, spent like two hours trying to research this, and it's a press release. There's like almost no data. A hundred and twenty six COVID patients were given tocilizumab and they had early disease.

They were not necessarily hospitalized. They were not, ICU patients like all the other, IL-six studies. So in early disease, it did not work in this press release. It's not peer reviewed, it's hard to say what this means. What does it mean that it didn't work?

Well, it didn't improve pulmonary symptoms, it didn't lessen ICU admissions, and it didn't change mortality rates in the one hundred and twenty six patients who were enrolled. The study was stopped prematurely during an interim analysis. They only had about one third of their enrollment done and they stopped because of these results. And I think they've aborted the study. But yet studies are still going to continue in tocilizumab, and I got three more that are also sort of preprints, preliminary results, not yet peer reviewed.

Again, this is the world we're living right now. I think we're gonna get really smart about COVID management starting in late July and going through September, October. We're gonna see the results of many studies with our our drugs, of which there are many of our drugs are in clinical trials. So let me briefly review for you three other trials where tocilizumab actually looked okay. An Italian study also, in this particular study, I can't remember the number, was fairly large.

When tocilizumab was given, it was given, it suggested it was more effective in people who were not yet on a mechanical ventilator, and these are hospitalized patients with COVID pneumonia. So it seemed to work best and the best outcome there was a reduced thirty day mortality rate compared to people who did not get tocilizumab. Fairly large study from the New Jersey Hackensack Healthcare System with, I wanna say it was like, you know, twelve hundred patients or something like that, survival rates were better in those who received tocilizumab fifty six percent compared to those who didn't get tocilizumab forty six percent, a reduction of about twenty four percent. Is that meaningful? Who knows?

And then lastly, a University of Michigan study of a 150 or so patients, half getting tocilizumab and other half not getting tocilizumab, the fatality rate was at one month different, fifty four percent versus twenty six percent. The the study the the populations getting tocilizumab or not were not evenly matched. The tocilizumab patients tend to be younger by ten years. They had a little bit less pulmonary disease and had lower D dimer levels. So, again, it's confused data.

It looks sometimes positive, but then there's a big but at the end of it. Same thing can be said for the negative studies with tocilizumab. Nonetheless, exciting to be, watching this as it happens and to be guiding, people who will call you on how to manage patients when they're using drugs like tocilizumab. Think you know need to know the data. That's it for this week.

Tune in next week for more. Go to the website to check out these citations, and, we'll see you next time around.