RheumNow Podcast FDA Hyperactivity (7.25.19) (1) Save

It's the 07/25/2019. This is the RheumNow podcast. Hi. I'm doctor Jack Cush, executive editor of rheumnow.com. This week in the news, when does a pain in the butt equal a diagnosis of sacroiliitis?

What about weight loss? Is it always a good thing, and does it always lead to good things or bad things? And does the FDA ever go on vacation? Well, I have evidence that says that they do. Not because they are in the news, but because they're in the news so much.

I think they've been on vacation, just got back, and have issued seven or eight new reports just this week. That's just from the FDA. First, we'll start out with the U Star study. You may be familiar with the study. It's been ongoing for years.

It's a study of nearly 1,500 patients with systemic sclerosis and looks at a lot of different outcomes. In this particular analysis, it looked at the predictors of worsening of systemic sclerosis. So, they looked at patients, in this cohort and about 700 of them that made up this analysis and it showed that worsening of the disease was associated with higher age, active digital ulcers, lung fibrosis, muscle weakness, and elevated CRP levels. I think that those are things we tend to look at, but maybe not as much as the obvious. We look at renal disease.

We look at worsening of lung disease by FVC or DLCO, but we probably should be paying attention to muscle weakness, CRP, and those digital ulcers. I tend to my biometric for scleroderma is often a band aid count. How many band aids do they have on their fingers to cover up the ulcers they have? That might be a good measure. A nice analysis looked at the association between ANCA associated vasculitis and IL-six levels.

This is important because we may end up using IL-six inhibitors in this kind of therapy. This is an eighteen month analysis, a serial longitudinal analysis of a moderate sized cohort, seventy eight patients with ANCA associated vasculitis, and showed that actually baseline IL-six levels did correlate with the presence of a PR3 ANCA, but not with MPO ANCAs. That IL6 levels did seem to associate with certain clinical manifestations including fevers, pulmonary nodules, pulmonary cavities, deafness, RBC casts, an interesting mix. However, soluble serum IL-six levels were not predictive of outcomes and responses to therapy suggesting that this may not be the right biomarker. I think it tells us that there might be a difference between PR3, ANCA associated vasculitis, and MPO as far as the biology that's involved, and maybe give us some insight maybe on therapy, but I think it's more about the biology of the disease, and I think it's a nice advance.

How it gets put to use is up to you. The Danish has studied a cohort of patients with, back pain and who had MRIs, trying to look at what the predictive features were of MRI and when would bone marrow edema amount to a diagnosis of sacroiliitis. They again, two zero four patients that included about forty one patients with axial spondyloarthritis, and they had all kinds of patients with all kinds of occupations, including postpartum women and all kinds of workers and whatnot. What they saw was that bone marrow edema itself is pretty non specific. Depending on the cohort they looked at, it was seen in three to thirty nine percent of individuals and really was not that predictive, especially in patients with non spondylolytic disease.

It turns out that the predictive features were mainly SI erosions and backfill, meaning marrow, being infiltrated by fat into going back into joint space where maybe there was damage or erosion, and then ankylosis obviously being most predictive also, axial spondyloarthritis. There were one or two women in the study that had postpartum low back pain who did have an SI erosion. So again, even SI erosion might be, misleading in a few patients. There's a limitation basically to what MRI can tell us. So we do know that weight loss is a bad, weight gain is a bad thing, and obesity is a bad thing for arthritis, especially rheumatoid arthritis.

It's a risk factor for getting disease. It's a risk factor for not responding to, many therapies, DMARDs and biologics. They actually looked at, this the issue of weight loss and weight gain in the Swedish obese study, the SOS study, that followed two hun two thousand and two patients, who had bariatric surgery and two thousand patient controls. That's bariatric surgery and RA patients, and then two thousand controls that didn't have bariatric surgery. Overall, two patients in this, amongst the two thousand bariatric surgery patients developed RA.

RA risk was, was not lower when you had bariatric surgery. The hazard ratio was only eight percent lower across one. It was not significant nor did weight loss, predict, developing or not developing rheumatoid arthritis. Turns out, however, that CRP and smoking were predictive factors in developing rheumatoid arthritis. So, it's kind of interesting that, a major loss of weight, whether it's with or without bariatric surgery did not protect against the development of rheumatoid arthritis.

This is at odds with what's been seen in patients, I think, with psoriatic arthritis where weight loss has been associated with better outcomes and and a reduced risk. There's been an FDA warning, and this is the first of many FDA warnings that I've got and announcements I've got this week. I'm pretty certain the FDA has been on vacation because this week, we got a whole bunch of FDA news. First, the FDA has a warning out to the public about using medications that may impair driving, and that's driving a car, a boat, a plane. Many of you are driving boats and planes, are you not?

Well, they say that if you're taking benzodiazepines, opioids, antidepressants, muscle relaxants, sleep meds, motion sickness meds, diet pills, and ADD meds, or stay awake drugs that you're at a much higher risk of developing, hazards when driving your vehicle, boat, or plane. Good recommendation for the population and for those of you who have boats and planes. The FDA has also approved a new several new biosimilars. One is Ruxients, r u x I e n c e. This is a rituximab biosimilar.

Rituximab dash p v v r. You know, we need those, suffixes to designate our generics in here in The US. In the rest of the world, they don't use the suffix with the biosimilar. They just call it biosimilar rituximab and in this case called ruxiinsulin. That's how they know, in The EU and elsewhere.

This is a biosimilar rituximab. It's approved for use, not in RA, but it is approved it is approved for use in non Hodgkin's lymphoma, CLL, GPA, and microscopic polyangiitis. This is the second rituximab biosimilar to hit the market. The FDA has also approved a new biosimilar of adalimumab. This one is brought to you by Samsung Bioepis, Epsys, who's going to be marketed in United States by Merck.

This, this particular product is called adalimumab dash b w w d, as in biosimilar, what would David do? And that's the suffix for that. It is, has the same indications as does adalimumab, and that would be rheumatoid arthritis, polyarticular JIA, psoriatic arthritis, psoriasis, ankylosing spondylitis, Crohn's disease, ulcerative colitis. Notice that the orphan indications are not an indication for biosimilars, only for the parent drug Humira. But don't worry, you can't get this drug in United States.

It will not be available until June 2023. AbbVie has made negotiations with this company to hold off its marketing in The United States. There's a lot of legal wrangling about the, protection of Humira in The United States that still is not yet resolved. The FDA has approved a generic version of febuxostat, you know it as Euleric, both the forty and eighty milligram pills. It's being licensed, to a, Indian company called Alembic Pharma, and so you might be seeing a generic version of febuxostat in the near future.

The FDA has approved a generic version of Lyrica pregabalin and its approval at its same doses for fibromyalgia neuropathic pain die from diabetic retinopathy and for postherpetic neuralgia and for partial onset seizures and neuropathic pain associated with spinal cord injuries. A regulatory, bit of news comes from The EU where, again, Samsung BioEpsis has made an announcement that the EU product for their adalimumab biosimilar called Imraldi has added a new, line about the drug's use, and this is important both in The EU and The United States because now the the line says the drug can be stored in a non refrigerated fashion with temperatures up to 25 degrees centigrade or at 77 degrees Fahrenheit, meaning room temperature for up to twenty eight days and still be usable, perfectly usable, and a 100%, effective. So, again, biologics don't need to be always refrigerated. Patients traveling with dry ice or big bags of ice and insulated things, don't need to do it. I tell my patients, take your biologic a few days earlier or a few days late, but if you must travel with it, take it, wrap it up in bubble wrap, put it in your briefcase, take it with you to Des Moines, Iowa where you're gonna be for a month and then take your drug as you may need to.

Now, that works for this biosimilar. It works also for, adalimumab in The United States and other biologics currently available. As you know, are several new major issues with the FDA and, decisions about new drugs. Yesterday, the FDA had a meeting of the arthritis advisory committee. 17 individuals met to look at the safety of a tyrosine kinase inhibitor, an anti fibrotic drug called nintedanib, n I n t e d a n I b, marketed as OLEV, o l e v, by Boehringer Ingelheim for idiopathic pulmonary fibrosis.

The drug has been studied in, almost what's 580 people who have scleroderma and, interstitial lung disease. Patients were randomized to nintedinib or placebo followed for fifty two weeks. In the end, nintedinib had a greater degree of protection against FVC decline. That was a primary outcome measure. It was forty five percent better than those that were treated with placebo.

This is a significant result in a disease where they're hard, it's hard to find significant results. Secondary outcome measures including improvement in skin as measured by modified Rodden Skin score was not significantly different and not better. So, this anti fibrotic drug seems to may have, seems to have some of, some effect on the lung. The question is, is it enough to be meaningful? This is only, I think, like, point four one mls per year or some very low number, but it is still 45% better than the placebo.

And it went up for a vote in front of these 17 panelists, included rheumatologists, and pulmonologists, and a number of other individuals, and the vote was 10 to seven in favor of approval for, the efficacy of the drug and the dosing that was being asked for, which is a hundred and fifty milligrams twice a day. It's this is not approved. It's gonna be evaluated by the FDA who will look at the results of the meeting and the advice of its panelists and probably come up with a decision somewhere in the next two, I would say, early as six weeks, late as late as, sixteen weeks. But that's just my guess. I have no inside track on this information.

Earlier this week, the FDA did approve aprimolast for use in the oral ulcers of Behcet syndrome, Behcet's disease. This is a nice addition. As you know, there was a 111 phase two trial published in New England Journal a few years ago. This last year, there was a 207 patient trial, a phase three trial, also published in New England Journal showing that patients were better with regard to the amount of pain from these oral ulcerations and better with regard to the amount of time that they had without having active oral ulcerations. Again, when this will take effect and be available, for patients who need this drug, It probably will take a few weeks before the company, which is Celgene, can amp this up.

As you know, Celgene and BMS are merging, but Aprimelast was not going to be a part of that merger. So, fate the of aprimilast and where it's gonna go and how it's gonna be marketed, especially for Behcet's disease remains to be seen. Take a look at my piece this week and my video this week on the war on rheumatoid arthritis. It's entitled part one, a walk on the moon. It's my plea to get you riled up about what we need to do to treat rheumatoid arthritis in the future.

Remember, we're all doing really good at what we do in managing RA, but we're still not perfect. We could do a whole lot better. There are still people who are dying. And if you continue to do what you're doing, you're gonna keep getting what you've got and know better. I'll end with a quote from JFK in 1962 who said, we choose to go to the moon in this decade and do other things not because they are easy, but because they are hard.

And because this challenge is one that we are willing to accept, one we are unwilling to postpone, and one which we intend to win. That's it for this week on RheumNow. Go to the website to see these citations and more. We'll talk next week. Take care.