Future Big BiTEs (6.28.2024) Save

It's the 06/28/2024. This is the RheumNow podcast. Hi, I'm Doctor. Jack Cush, executive editor of roomnow.com. We're on the downside of EULAR.

Thank God that's over. We put out a lot of content I hope you've enjoyed it. If you haven't consumed any of it I suggest you go back and start reviewing it. I'd start with the lupus panel discussion and the psoriatic arthritis panel discussion the day one two three four daily recaps those are good starts or maybe just Artie Cavanaugh and I doing the EULAR Rheumatology Roundup. We got all new podcast this week where I'm going give you new information not EULAR information.

Those of you who are seeking relief EULAR. Let's begin with some regulatory decisions that came up the last few weeks while we were actually at EULAR. One, the FDA has approved cerilumab or Kevzara for the treatment of polyarticular JIA, that's a welcome addition. Also, the FDA has approved upadacitinib or RINVOQ also for polyarticular JIA and also for pediatric psoriatic arthritis. We're talking about kids at two years of age or older who had an inadequate response to one or more tumor necrosis factor inhibitors because it's a JAK inhibitor.

Right? You gotta stop or use the the TNF inhibitors first before you get to a JAK. That's in line with the adult recommendations. And lastly, the FDA has also approved, rizenkizumab, the IL twenty three inhibitor also called SKYRIZI for moderate to severe active ulcerative colitis making it, I think, the first IL twenty three inhibitor approved for both forms of inflammatory bowel disease, that's based on two large well done phase three trials. Another big ticket item in the news, probably not too too important to you but maybe important to your patients was the JAMA report, very large report on the efficacy of multivitamins.

Surely, you must have a guess on this one. It's not hard to miss. Three large prospective trials of multivitamin use, general multivitamin use in generally healthy adults, over 390,000 individuals showed it did not more, alter mortality risk one bit. So this is like a lot of evidence that's out there that a lot of the things that patients do for themselves, especially over the counter use, may not always be good. There was another big report this this week about too many adults with no cardiovascular risk factors are taking daily aspirin when they probably shouldn't, that the risk is higher.

Well, same thing here with the multivitamin. People take it because it's a good health thing to take a multivitamin. I take a multivitamin and that's so that I can eat badly in between, but obviously that doesn't seem to work in preventing disease or having a true wonderful health benefit. Do I encourage it? Yes.

It's a cheap intervention, it's not going to harm anyone and if it gets people to believe they have some control of their health, well it's the first step of many in taking control of your health. Why not? Another drug is in development, another IL-seventeen is in development, this one from Moon Lake, they made an announcement this week on their dual IL seventeen a and f inhibitor for use in psoriatic arthritis. They have an expanded phase three program that they're launching. I think it's gonna be 1,500 patients in two very large trials with an ACR 50 endpoint at week 16.

We can look forward to this. We'll be a competitor to bimekizumab who will probably get to the market a lot faster than they will, but know if you will that there's a lot of IL-17s in play and, we're about to now get a bimekizumab and at the end of the year maybe if we're lucky, for psoriatic arthritis to prove for psoriasis where it's doing well and then this other one is following suit and that might be another year or two away. So a lot happening, with the companies and regulatory agencies in the two weeks we were away at EULAR. I found this interesting report report about cancer risk in ankylosing spondylitis. As you know, I'm interested in cancer risk in our patients and the effect of drugs.

I don't think there's much. I think it's all from the disease and inflammation. Well, in this systematic review, actually, it's a literature review of over 330,000, individuals with ankylosing spondylitis showed that there was a overall higher risk of sixteen percent, significantly higher risk of all cancers. That's the relative risk. Interestingly, when they did it, the analysis by geography, it was higher in Asia, but not in Europe, didn't say anything about United States.

The AS patients in this analysis were at higher risk for both cancer bone cancer, thyroid cancer, multiple myeloma, leukemia, kidney, and prostate cancer, also non Hodgkin's lymphoma with relative risks. The highest was for bone related cancer at three point three fold increased risk. All the other ones had about a forty to seventy percent increased risk that was significant. What else do we see with cancer in our patients? Well, myelodysplasia, a myelodysplastic syndrome, it's on its way to something else, is it not, or is it an entity unto its own?

Happens in a lot of our patients, does it not? This one systematic review of autoimmune disease and myelodysplasia found that amongst myelodysplasia patient patients, seventeen percent have autoimmune disease. And there was no difference if you had autoimmune disease if or if you didn't, with regards to mortality figures, there's a large spread here. Fifteen to sixty seven percent risk of, I think, five year mortality. But the question really is, why does this relationship exist?

Why do autoimmune patients, RA patients, lupus patients maybe have a slightly higher risk of of myelodysplasia? It reminds me of that old cartoon, happy face, normal, the sad face cancer, and in between is autoimmune disease that is part of some, you know, genetically driven, epigenetic driven, environmentally driven continuum from normal to abnormal with cancer being the most abnormal, that clearly there's always these relationships between autoimmune disease and, malignancy. So scleroderma. Interesting report. Actually, this is from ULAR.

Abstract o p zero zero one three, found interesting. It's an analysis of the very large U Star cohort database. Over four thousand patients with the systemic sclerosis, they found that SSA antibodies are found in fifteen percent of scleroderma patients. I wouldn't normally even check for SSA antibodies. Maybe I will now because this report found that it's an independent risk factor for the development of lung fibrosis and maybe more severe lung disease.

So the odds ratio here is one point two four. That was a sort of twenty four percent higher risk of of lung fibrosis in systemic sclerosis if you are SSA or Rho positive. Maybe we should be checking SSA and SSB antibodies in those patients and not necessarily for Sjogren's. Another study on systemic sclerosis looked at the cause of death. This is a large Finnish cohorts study of three hundred and thirty one patients with systemic sclerosis and found that the that nine that at three hundred and thirty one, there were ninety one deaths at the five year survival rate was eighty eight percent, ten year survival rate was eighty percent.

I think that kind of jives with what I see in my years of practice. Turns out that the most common cause of death was scleroderma itself. Thirty five of those ninety one deaths were due to scleroderma. The next most common was ILD, scleroderma related ILD, and thirteen was ninety one. So it's like one out of seven from ILD and one in three from scleroderma itself.

Now what is scleroderma that would kill you? Well, you figure in that that blank, but that's how the physicians coded it as the cause of death. The drug the drug that we like to keep lupus patients out of trouble is hydroxychloroquine. It, you know, it's got pregnancy benefits. It's got benefits with lipids.

It's got benefits on survival. It's got benefits on blood thinning. It's got benefits on diabetes, you know, it's like what doesn't hydroxychloroquine do? This study of nearly three thousand patients taking hydroxychloroquine. I want to say this is actually from Canada, that five eighty four or one in six of the patients were hospitalized more than once for lupus.

And it turns out that, if you were taking, inadequate doses of hydroxychloroquine, you are more likely to be hospitalized. So doses of less than five milligrams per kilogram per day or doses of less than four hundred milligrams per day on general were associated with an increased risk of hospitalization for lupus with a fourfold or a three point fourfold higher risk for those two markers or or two cutoffs on dosing that I mentioned, less than five per kilogram or four hundred per day. Again, you know, it's the magic drug that, benefits all in patients with lupus. I got my next two reports are are two really kinda cool things that I think are happening that you should be aware of. One, I'm running across a number of different reports where JAK inhibitors are being used as adjunctive therapy to patients who have cancer or to patients who are taking checkpoint inhibitors.

And in both, whether it was Hodgkin's or a solid tumor or in the case of, someone receiving a PD-one or PD L1 inhibitor that the use of itacitinib in lung cancer and Hodgkin's disease, or with ruxolitinib, in with checkpoint inhibitors, better outcomes in the cancer patients and we're not just talking about with the checkpoint inhibitors that they because they're on JAK inhibitors, they didn't develop the adverse events related checkpoint inhibitors that we see, I don't think the numbers were enough that they would have enough of an incidence that they could come comment on is preventative strategy there, but they were really looking at better outcomes on cancer survival and length of survival. So is there a role for just like the cardiologists are thinking, is there a role for inflammation control and better control of heart outcomes? Well, we know the results of those studies with methotrexate, canakinumab, etc. But now in cancer, might there be a role for, you know, background therapy with the drugs that we use? In this case, the JAK inhibitors because they're well tolerated and they're they're expensive and not sure how or why those were chosen.

Would would patients do just as well if they were taking methotrexate or azathioprine? I think this is a further evidence for the fact that the cancer doctors shouldn't be discontinuing your drugs that you give for your patients with inflammatory arthritis or autoimmune disease when they're managing the cancer. There's really no evidence that it's going to worsen the outcomes. And I think this is I think this is a trend that we're going to see more of. JAK inhibitors and maybe other DMARR therapy or biologic therapy as adjunctive therapy and cancer control.

The other ones are these drugs that were got their a fairly good play at EULAR, and that's these bites. You can actually say bite me and get away with it and not get slapped. These stand for bispecific T cell engagers that basically are able to kill better kill B cells and lead to B cell depletion by engaging T cells. So there's a number of them that were, you know, mentioned and studied in preliminary ways at, at EULAR. This is a recent report of a c d nineteen, coupled with a c d three bite.

The drug is called, blinatumomab. Blinatumomab, it's an IV preparation given to six refractory RA patients who failed multiple biologics and DMARDs led to pretty brisk and effective B and T cell depletion coupled with a rapid decline in disease activity measures, synovitis, autoantibodies, and was overall safe. Patients had a brief, rise in temperature, a brief rise in c reactive protein levels, but no evidence of cytokine release syndrome. These are like competitors to the CAR T cell specific therapies that can lead to B cell depletion, of course. But remember, those are autologous, need to be prepared with the patient's own blood.

These are off the shelf. These are not dependent on these are allogeneic antibody preparations and other preparations that will be used off the shelf and will compete with this next generation of CAR T cell therapy going forward. Again, I think this is a future cool thing that we're gonna see. Two more reports. One that's gonna just make you feel good about you.

These are always the best kinds of literature that reaffirm that what I'm doing is perfectly fine, and that is I use methotrexate with no fear of worsening of interstitial lung disease. That's a special kind of stupid in my mind. Methotrexate causes an acute hypersensitivity pneumonitis, which does not look like interstitial lung disease at all or behave like it, and we've talked about this here before. This is an analysis from JAMA this week that says that patients with dermatomyositis have in based on literature reports, to a twenty three percent risk of developing interstitial lung disease. And and this particular study looked at three hundred and fifteen dermatomyositis patients taking a number of different immunomodulators including methotrexate as their first line treatment.

So about a third of the patients received methotrexate compared to sixty four percent who did not. Both groups had an equal number of of ILD events, roughly seventeen with methotrexate, sixteen percent without methotrexate, thus no significant increased risk of ILD when you're taking methotrexate for dermatomyositis. And this is just one more bit of evidence that you can provide to your pulmonary colleagues who don't seem to wanna recognize this literature. Lastly, we reported on this use of SGLT two inhibitors in autoimmune disease and lupus at past ACR and ULAR meetings. This finally made it into publication with JAMA drawing from thirty one thousand patients with I think lupus and diabetes.

They did a propensity matched pairs cohort analysis of fifteen hundred, seventeen hundred plus on SGLT2 inhibitors, and those that were not, three thousand five hundred patients, the two to one match. The patients were 57 years old, eighty five percent women taking an SGLT2 inhibitor if you had lupus and you also had diabetes, number one, lowered your risk of lupus nephritis by forty five percent. Number two, lowered your risk of dialysis by sixty one percent, lowered your risk of transplant by eighty six percent, lowered your risk of future heart failure by thirty five percent, and lowered all cause mortality by sixty five percent. You've probably seen the trend. SGLT2 inhibitors and GLP one agonists being used in patients without diabetes to better manage outcomes in heart and heart failure patients and in patients with chronic CKD, bad CKD.

Mark my words, we're gonna be seeing the same drugs being used to better manage outcomes in RA, in lupus, in gout, and lord knows what else going forward. So I think in the future, we'll be seeing combined, if you will, combination therapy with a biologic or targeted synthetic along with these diabetes drugs that have these tremendous all cause mortality benefits and then also end organ benefits. I think this is a cool thing. Hopefully you agree. That's it for this week on the podcast.

Hope you enjoyed it. Go to the website to check out these citations and more. Next week is the July 4, Independence Day here in America. RheumNow staff is on vacation. I'll be chasing them around to see if I can get them to do some work, but we will be doing the best of reporting next week, including next week's podcast.

I hope you enjoy it. We'll be back in two weeks. Take care.