Hydroxychloro-King (3.7.2025) Save

Hello, everyone. It is the 03/07/2025. This is the RheumNow podcast, and I'm Jack Cush with rheumnow.com. This week, we have some regulatory announcements. We have discussions about sleep and interesting news about the emergency room and about hydroxychloroquine.

So this week, we saw a few things that I thought were interesting. Genentech has, announced that the FDA has, accepted their, SBLA, that's the supplemental biologic License Application for their drug called Gazyva, G A Z V Y A, the anti CD20 monoclonal antibody also called obentuzumab. And, you know, a lot of anticipation about this drug and its use and utility, in lupus nephritis. So, when you submit a new biologic, it's called a BLA. When you submit a supplemental BLA, it's for an extension of a drug that's already FDA approved.

So, obentuzumab is actually FDA approved for, the hematology oncology space, And now we're going after a lupus nephritis indication. We talked about that in the New England Journal article recently published. So this application is really based on positive results from that phase three Regency study. It's now expected that this will result in an FDA decision, yay or nay, in October 2025. AbbVie has received a positive indication, sort of a thumbs up from the EME CHMP, that they render an opinion advising the EMA to either approve a drug or not.

The positive opinion usually results in approval for upadacitinib for the treatment of giant cell arteritis. Other FDA news was the FDA granting priority reviews to five drugs, four that I thought were actually, it was like seven drugs in the report, and I think there were four or five that were important to rheumatology. Nipocalimab was misspelled in the report and in the tweet. This is the J and J FCRN neonatal Fc receptor antibody that we talked about at ACR being used in Sjogren's. Well, anyway, the priority review is for this FcRn antibody and its use as an indication in myasthenia gravis.

There are other drugs, VyvaGard, I think is the name of it, that is actually approved. It's an FcRn antibody for use in myasthenia gravis. UPA, as we said, got a positive opinion in the EMA in Europe, but now the FDA is going to review the AbbVie application for its JAK inhibitor upadacitinib for giant cell arteritis. Namestat, a Boehringer Ingelheim drug, a PD4B inhibitor, and its indication is going to be for idiopathic pulmonary fibrosis. And then there's another anti CD9 monoclonal antibody from Hansen called inalizumab, and that's going to be for IgG4 related disease.

So these are regulatory happenings that are going on as we sleep and breathe rheumatology. Two reports that talk about sleep that I think we should, take note of. Sleep is a major problem. Don't know how you can practice rheumatology and not address sleep in every patient at every visit. I mean, it's a big part of my practice.

Sleep is a major it's a harbinger for what's going on with a patient, musculoskeletal wise. On the website, I have sleep hygiene as a handout that you can download. I've gone over sleep hygiene so many billions of times in my practice, I can recite for you the 12 items without even looking at it. Number five says, Your bed is your special place sleep only. Do not read or watch TV in bed.

Your bed should be free of remote controls. No food, children, pets, snoring spouses, computers, magazines, or cell phones. Your cell phone is charging in the kitchen or living room while you're asleep in the bedroom. That's only number five. Anyway, a prospective cohort study from the Nurses Health Study, includes 70,000 nurses followed for many years, looked at the associations between sleep disturbances and sleep apnea, and progression to disability, and looked at in that cohort of seventy thousand patients, there were three ninety two with multiple sclerosis, seven thousand three hundred with diabetes mellitus, and twenty five thousand with osteoarthritis.

And yes, having either sleep apnea or a sleep disturbance gave a forty to fifty percent increase in developing disability if you had osteoarthritis or diabetes, but not multiple sclerosis, interestingly. And then also the reports of daytime sleepiness as a symptom was, I think, another symptom of bad sleep at night. But daytime sleepiness was also associated with an increase in disability progression in patients with osteoarthritis. So sleep, you got to pay attention to it. You can't ignore it.

Another study looked at the loss of good sleep being linked to all cause mortality. This is a United States study that showed that two thirds of the population that was under study had a five year sleep trajectory that was not good, and that resulted in a twenty nine percent increase in all cause mortality. It's epidemic in Western cultures. In other cultures, in poor cultures, it's not as epidemic. It's a function of modern times and televisions and screens and cell phones and lord knows what else, but if you don't work at it, it's going to be the thing that drags your patients down.

They're already gonna have problems to deal with that are musculoskeletal, autoimmune, rheumatic, whatever, but this just makes everything worse. Just like depression makes everything worse. You've got to pay attention to that as well. A study looked at the risk of cancer, looking at twelve thousand RA versus thirty eight thousand controls, and showed that overall, no overall risk of cancer when you're exposed to a JAK inhibitor, odds ratio is about one point zero four. Also, no increased risk of cancer if you're exposed TNF inhibitors or biologic DMARDs in general.

But when they looked at what JAK inhibitor use was associated with, it was associated with significantly more lung cancer, especially in males. Lung cancer, a significant increase with a hazard ratio of one point four. It went up in males to two point one two. JAK inhibitor use was also associated with less risk of breast cancer, where there was a thirty eight percent decrease. Odds ratio is 0.62, obviously in women.

But that's not really TNF I mean, JAK inhibitors being associated with lung cancer and less breast cancer. No, it's actually what happens in RA. There's more lung cancer in RA. There's less breast cancer in RA. And the JAK inhibitor is one of the common drugs that's used to treat RA, so it's along for the ride.

Don't misinterpret the data. Two good reports this week. One was an overall full read review on hydroxychloroquine. If you're hydroxychloroquine fan, it's a good read. It discusses a lot of things.

You can check it out on the website. We tweeted about it as well. And then there was this article about from JAMA Dermatology, I believe. And it's a retrospective longitudinal study that basically says taking hydroxychloroquine slows the progression or prevents the progression from cutaneous lupus only to systemic lupus. So this is a study of two eighty six consecutive patients with isolated CLE.

And then in that two eighty six, one hundred and eighty six received hydroxychloroquine, and one hundred received either topical steroids with calcineurin inhibitors. And overall, about thirteen percent of their two eighty six patients did progress from CLE to SLE. But based on your therapy, there was a big difference. If you're on hydroxychloroquine, it was only four point eight percent. If you're on a calcium urine or steroid group, it was twenty seven percent.

That's almost a six fold higher rate. So early initiation was therefore associated with a eighty seven percent reduction in future risk of progressing to SLE. By the way, using hydroxychloroquine early in the case of CLE also limited development of severe organ involvement with SLE. Again, another drop by this looks like eighty four percent. A risk ratio is zero point one six.

Again, add this to the list of the many great things hydroxychloroquine does in patients with lupus. And yes, it's vitamin H. If you've got lupus, you should be on it. And I was just in Salt Lake City, and I was asked a question about hydroxychloroquine in RA. I think it's the same in RA.

Not as well researched, not as well demonstrated, but the add on value of hydroxychloroquine in RA is very strong and and should be considered. It's not just for mild cases of RA only. Another study this week from I want to say it was a JAMA report as well, looked at the and it's a study coming out of Western Canada, out of Alberta, I believe. And they looked at almost five thousand patients with psoriatic arthritis and almost fifteen thousand with radiographic axSpA. And they looked at their use of emergency departments and urgent care centers.

And I think some sort of surprising information was seen here. They categorized visits to either the emergency room or urgent care centers as either being resuscitative that was class one urgent I mean, emergent class two, urgent class three, non urgent class four, and five was, I think you shouldn't have done it. I'm not all that worrisome. And they found that overall, forty eight percent of PSA patients and thirty six percent of ACSPA patients were accessing the emergency department or urgent care centers annually. Isn't that a little bit high?

And in the paper, they reviewed it and showed numbers as low as five percent and numbers as high as thirty percent. So this seems high, but a lot of this is Western Canada and rural Canada. And that was one of the points of the paper that rural patients are more likely to use the emergency room and urgent care centers for their care. What was surprising about this report was that less urgent and non urgent ED visits were common, comprising either forty four or fifty percent of the overall visits that were seen. So again, most of the use of the emergency room was classified as not urgent or less urgent.

Visits were mainly for infection or injuries. Like eleven, twelve percent is, I think, the top number there. But in presentations to these centers for inflammatory arthritis were really infrequent, less than two percent. So they're not going to these urgent care centers for their arthritis care. They're going for, you know, infections and injuries.

Not all of them, again, need to be there. So it drives up health care. There's a clear cut need for education about how to get care if you have PSA and It's not maybe not surprising that a high percentage of them go because patients with PSA and axSpA do have a significant amount of comorbidity and depression and obesity and other things. But again, this is a public health issue that can be remedied by planning and education. I want to let you know, obviously, RheumNow Live is over, but it is available for those of you who did not attend, but would like to have seen some of the things we've talked about in the last several weeks.

It is available for on demand, and you can register for the on demand course. See all the videos. There was seven TED Talks from rheumatology experts. There were 21, 22 lectures and Q and A panels with our speakers, and taking questions from the audience and from each other. If you register, you can you have six months or more to look at the content.

You can download all the slides, all the handouts, all the pre reads. You can do the pretest, pre learn. At this point, though, I don't think you can get CME. It's really to do it for your education. So look for that.

Also on the website this week, as I said, there were full read reviews on hydroxychloroquine, another good full read review on relapsing polychondritis and concerns about tracheobronchial involvement there. And then I'll encourage you to record your question on the website. You go to bottom left and ask Cush anything. Click on that, and you can record case or your question for me, and I can answer that for you and the audience on future episodes of this podcast. Hope you enjoyed it.

Take good care of yourselves. We'll talk next week.