Treating During Pregnancy (11.14.2025) Save

It's 11/14/2025. This is the RheumNow podcast. Hi, I'm Jack Cush with RheumNow. This week good news on Sjogren's, good news on treatment in pregnancy, another treatment option for CPPD, and a new guideline on lupus. So let's begin with lupus.

A study from Western Australia looked at the incidence of lupus associated interstitial lung disease. We've talked a lot in September about ILD, so much about lupus. You know, it's a big deal in scleroderma and in myositis, the MDA-five patients for instance, and in RA, right? And then, you know, lupus is kind of thrown in, but what's the real incidence? Here, a cohort study of eighteen fifty four patients found that three point eight percent had ILD related to lupus.

And yes, that was significantly higher than controls, 26 higher 26 fold higher, I'm not sure what the controls were, but the risk factors for developing ILD in lupus was older age, smoking, and serositis. And not surprisingly, lupus patients with ILD have a significantly higher mortality rate. ILD is a bad player no matter who it shows up in. Genentech reported the preliminary top line results of an allegory study. This is a phase three trial with obinutuzumab, you know, that's the CD20 monoclonal antibody that's going to be used in lupus nephritis and lupus in general.

So this was a phase three double blind randomized placebo controlled three hundred active lupus patients. The outcome was an SRI four primary endpoint at week fifty two. This monoclonal antibody depletes b cells better than rituximab, and in the oncology world looks to be a much better world at treating b cell cd20 related lymphoma especially. So it met all its primary and secondary endpoints, we don't have the actual numbers there, but that's going to be presented in publication soon. As you know, the drug was approved in the last few weeks by the FDA.

So, at ACR there was another presentation on a new lupus guideline. Last year was all about the renal lupus guidelines, which were great, helpful, instructive, and debatable, right? Now, Lisa Samaritano, who's led a lot of these guidelines, and thank you Lisa Samaritano and your team for all the hard work, she presented the guidelines on basically lupus that's non renal, so non renal lupus. And I like the guideline, for several reasons, and then I have my my but kind of statements. The bottom line is that there were 65 recommendations.

Almost all of them were conditional, with low or very low evidence. So there's a real art to managing lupus, right? The three, strong recommendations that are evidence based was number one, everybody should be on Plaquenil. Number two, everybody should go on prednisone five mil, but they should be off of or at less than five milligrams within six months. And number three, therapy should be escalated in people not responding.

Number three is kind of like a, you know, knucklehead statement, is it not? But then they've got a ton of recommendations by organ systems: neuropsychiatric, articular, skin, etc. And I'll just read for you a few of these, and these are the ones that are conditional and very low evidence, but this is kind of the way you practice. And now the ACR is telling you that what you're doing is good. So, asymptomatic neutropenia or asymptomatic lymphopenia, if you have no symptoms, that you do not automatically get an escalation of immunosuppressive therapy.

Steroids, biologics, you know, azathioprine, microfilm No. Without other events of lupus activity they strongly not strongly they conditionally recommend against it. Thrombocytopenia, that's asymptomatic and chronic with platelet counts less than 30,000, they do recommend that you start a steroid with an additional therapy. Mycophenolate is a thioprine, calcium neuroin inhibitor, cd20, belimumab and or IVIG because that must be indicative of, indicative of lupus activity that needs to be better controlled. Now let's get into thrombocytopenia that is symptomatic, meaning they have active bleeding.

They recommend glucocorticoids with either IVIG or an anti cd20 in addition to conventional therapy. And same for hemo hemolytic anemia, that's symptomatic meaning ischemic manifestations etc. The same thing: glucocorticoids with IVIG or an anti CD20 on top of your baseline therapy. So, it's a good document to hold near, and we do like guidance documents, I think this one was helpful. A report from JAMA Dermatology looked at severe cutaneous reactions associated with allopurinol.

So they did a match cohort study, they found sixteen patients with either Stevens Johnson syndrome or toxic epidermal necrolysis associated with allopurinol use, and they basically assessed these people, and that 16 cohort was matched one to 10 with a non severe cutaneous adverse reaction, they call it SCARS, one hundred and sixty patients. And they found that, as we know, HLE B5801 is associated with allopurinol induced severe cutaneous reactions. We know that that gene is found in Asians and blacks and less common in The United States. This study, by the way, was done all in The United States. They also found another gene, HLAA3402, and this had sort of the same amount of risks.

But the point of the paper was to say it's not just B fifty eight zero one, but it's this A thirty four zero two, and then also that, it does occur in The United States, more commonly in blacks, and then Asians and others, but more than a third of people with these cutaneous reactions did not have these genes. So we don't have the complete story yet, and I don't know that based on this data I would be screening people going on allopurinol for B5801. Asians, I probably would, but nonetheless, I think it's something to think about. A study in IBD looked at infection rates, and I published this because, you know, you know the numbers associated with RA associated serious infection, events, SIEs. The historic number in the pre biologic era was nine SIEs per 100 patient years.

So out of one hundred patients followed for a year, with RA any therapy, nine would get an SIE. Septic arthritis, sepsis, pneumonia, opportunistic infection even. Okay? Then the biologics come along, and we find that the numbers generally run, you know, about four to six, three to six per 100 patient years, less than the historic controls. Alright?

And we know that when you use really high doses, like higher doses ten milligrams per kilogram of infliximab, it goes up to seven plus. It gets closer to that nine number. But why do you see lesser numbers in psoriasis and other conditions? And it turns out it's the background condition that determines the baseline rate. So, in this study they show that IBD is like RA.

It's what I call a dirty condition, it has a higher baseline risk for these SIEs. So a study of five thousand IBD patients, and they looked at them, and these are patients, I'm sorry, IBD patients, that were either had ulcerative colitis or Crohn's disease. Ulcer colitis, the rate was five point five. Vetolizumab was seven per one hundred. So overall the number was five point five.

It was higher with vedolizumab. In Crohn's, the SIE rate was again still higher than ulcerative colitis seven point nine, and vedolizumab was six point five. So the question is: do the biologics add to the risk over the background risk of the disease? Maybe a little bit, and only in the worst candidates, and only when you use the highest doses. That's the takeaway, and why I reported this one.

Another study looked at whether TNF inhibitor exposure in utero would increase the risk of infant serious infections. So, a meta analysis of 10 studies showed that in utero exposure did not increase the infant severe infection rate, and that's four clinical trials. And then there were two clinical trials looking at breast milk. The mother was taking a TNF inhibitor and also did not show increased rates of infection in the child. Infant vaccinations were unaffected by TNF inhibitor use, but they do recommend BCG, if the mother is BCG vaccination of the infant, which we don't do in The United States, but is done internationally.

That should be delayed if the mother is on a TNF inhibitor, when the child was being born and whatnot, because, BCG is basically a mycobacteria, TNF inhibition would make the the child, the infant, at higher risk of disseminated TB, and that's been reported multiple times. So yeah, you don't want to use BCG at the time of birth, but everything else as far as vaccination, seems okay. Another study looked at, claims data on women with inflammatory diseases, IMiDs, you know, that includes both skin, GI, and rheumatology patients. Seventy thousand patients, sixty nine thousand births, and seven point one percent were exposed to at least one TNF inhibitor during pregnancy. And another percentage, half that percentage, was well actually almost the same now, about six percent were exposed with TNF inhibitor during the postpartum period.

They found the TNF inhibition and exposure did not increase SIE risk during pregnancy, hazard ratios 1.39, confidence intervals 0.95 to two point zero, not significant, and even lower for, and not significant for, postpartum exposure. So again, good news about how to treat women who become pregnant, and that aggressive treatment of them with biologics, especially TNF inhibitors, appears to be very safe. Okay, so what else we have? We have another, pregnancy, study that looked at scleroderma, And this is the, Swedish birth register that looked at, pregnancy outcomes, in scleroderma women, nine forty one, who had scleroderma, let's see, they had these outcomes after the diagnosis of scleroderma, nine forty one, or within three years of diagnosis at 39, or before three years of diagnosis at eight thirty nine. So they said that overall, scleroderma women have an increased risk of adverse pregnancy outcomes.

That's like miscarriage, preterm birth, intrauterine growth retardation. It would include malformations, but there are no malformations here. So, they have an increased risk of adverse pregnancy outcomes post diagnosis. So the diagnosis is already established, the pregnancy happens, they get more APOs. We've seen that in RA, we've seen that in lupus, right?

And the outcomes here were mainly preeclampsia, almost fourfold risk, preterm birth threefold risk, c sections two and a half old risk. But they also showed increase in adverse pregnancy outcomes when they were within three years of having a diagnosis of scleroderma. This kind of speaks to the point that there's a preterm condition that's stewing before they actually develop clinically manifest scleroderma. And those immunologic abnormalities may translate to higher risk even before you know you have the diagnosis. So, interesting.

PMR. What's the differential diagnosis of PMR? In my book, you know, it's older Caucasians with stiffness and joint pain, but generally girdles, stiffness, acute phase reactants, and and did I say stiffness, did I say older, did I say white? Okay. And yeah, that's the bulk of the business here.

Is it not? Yeah, I know you have a patient who's green and not quite 70 years old, but honestly that's what PMR is. But when it's confused it's often rheumatoid arthritis, right? In this study, from one center, seventy seven patients referred to rheumatology for possible PMR diagnosis found that there were several of them, seven percent, that had, a viral infection, parvovirus B19. What?

And these, seven percent of these patients, so it's like six or seven patients, actually it's five or six patients, had oh, they all had arthralgia, okay? They all had PMR like symptoms, bilateral neck shoulder pains with prolonged morning stiffness, low grade fevers, and high acute phase reactance sed rate and CRP, but none of them had hip pain it was just upper extremity. Interesting. Four out of five were male, the mean age was 55, less than you would expect for PMR. I put it up because now it's in the differential.

I would not have previously assumed that parvovirus B19 could be a possible Oh, and by the way, none of these patients with B19 masquerading as PMR were RF positive or CCP positive. So, we worry about aging and the rising risk of osteoarthritis. A recent report from the Global Burden of Disease study, it was in rheumatology, talked about a growing burden for a subset that you wouldn't normally consider, and that's middle aged adults between 40 and 59 years of age. In recent years the incidence of prevalence of OA in middle aged adults has risen one hundred and twenty four percent from eleven point eight million in 1990 to twenty six million in 2021. What?

Fifty six percent of incident cases, thirty eight percent of prevalent cases occurred in the middle age group. This is seventy percent higher than its occurrence in the elderly over age 60. I find this surprising, but then again is it really? Why would forty nine forty to fifty nine be getting it? It's got to be lifestyle Growing frequency of obesity in our population, and then other lifestyle factors that must be going into this.

They did find more of it in high income Myositis. Let's talk two reports on myositis. A South Korean study of four eighty one patients looked at myositis associated cancer, which they found in twelve point nine percent, or sixty two out of four eighty one. That's your risk. I've always thought that the risk is highest in males that are older with dermatomyositis.

In their analysis the cancer risk factors were age, older male, bingo current smoking makes sense and dermatomyositis and also having TIF1 gamma antibodies. But they also showed a lower risk of cancer in those with the antisynthetase syndrome, overlap myositis, those with arthritis, and ILD. So you had, what they call the scrim score, s c r I m, which is a number of factors put together and it gives you an area on the curve of point eight five, suggesting a high predictive value. You know, maybe we could use this in practice. I think many of you, when you're making a diagnosis of polymyositis, dermatomyositis, automatically looking for cancer.

I don't. I never have. I do health maintenance. You know, I get what they need based on their age. And then if they get other symptoms suggestive of cancer, yes, I'll evaluate it.

But you remember at ACR three years ago, a plenary session, laid down new guidelines on how to develop risk categories. And they had, you know, other than minimal risk, they were doing really invasive evaluations for cancer that I did not agree with and they didn't have any data for. They were just throwing it down, hoping that someone's now going to study this. Again, how you handle this is gonna be up to you, but we need guidance that's based on data and not just based on strong opinions. Like mine, for instance.

Another study looked at mortality in dermatomyositis. I worry about dermatomyositis when it gets into the hospital. This is a study of one hundred and fifty three adults with dermatomyositis who were hospitalized and what were their outcomes? Well, unfortunately ten percent died. Sixteen out of the one hundred fifty three died.

Risk factors for death from dermatomyositis in the hospital was having a rash 12 fold higher risk if you had active DM rashes eighty one percent versus thirty four percent in those that didn't. Wow! ILD not surprising we said ILD is a bad player and imposes a high morbid and mortal risk no matter who. This gave you a six fold higher risk. And then an elevated neutrophil to lymphocyte ratio you have a twenty nine percent increase for every one unit increase.

So, it was an elevated NLR seen in twelve point five percent of those who died versus four point nine percent versus from those who didn't die. So, a more sort of a doubling of risk. Anyway, for me, the worrisome factors when you get admitted to the hospital are admitting features of shortness of breath, ILD, right? Dysphonia, dysphagia. They are now at high risk for aspiration which is going to worsen their lung outcomes when they already have a risk of ILD, right?

And that's pretty much my my red flags that were not borne out in this study. I liked another study, that this week that we reported on, IL-one inhibition in calcium pyrophosphate deposition disease. I think we had a study from EULAR three years ago that was an IL-one control trial, but it was small. And can you use an IL-one inhibitor in pseudo gout or CPPD? Well, this was a meta analysis of five observational studies in one randomized controlled trial, a total of 84 patients that used the drug anakinra, the IL-one inhibitor.

And they showed that in patients with acute flares of pseudogout, of CPPD or pseudogout, that they had positive clinical responses by physicians of seventy five percent, reduction in pain scores by half, significant reductions in CRP levels by 62 points on a sixty two milligrams per liter, okay, or zero point six milligrams per deciliter drop, and a reduced number of joints minus five, reduced number of swollen joints, minus 3.6, and as you would expect other side effects that you see with IL-one inhibition: injection site reactions, rashes, bacterial pneumonia and neutropenia all reported. I think this is a reasonable choice for someone with acute pseudogout that hasn't been well controlled on existing therapy. Alright, one last report. While we went to ACR, Nipocalimab, the, FcRn, blocker, that's been studied in RA and a few other conditions, has been studied in Sjogren's disease and that's the DALIA study. It was reported in, Lancet Rheumatology, this is a phase two trial of patients with, active moderate to severe Ro positive Sjogren's syndrome with a clin SDI score of grade of six or more, and they were either given placebo or nipple calumetcalimab five or fifteen milligrams per kilogram every two weeks for a total of twenty two weeks.

That was the endpoint. The endpoint was the reduction in the clin s dice score and yes the higher dose the fifteen milligram dose not the five milligram dose was associated with significant reduction at week twenty four. Again, the least squares mean was minus 2.65 and that was significant at p dot zero zero one eight. You know this is a positive phase two trial. We need to see how they're going to do in phase three.

As you know we just had the, results enalumab from Novartis reported at ACR that also gave positive results, but only when they combined two different studies together to get positive results at multiple time points. Otherwise both studies seem to only get positive at the end. Both these all these studies are hampered by high placebo response rates. That's the big problem. So, for them to prove with enalumab, the other B cell targeted monoclonal antibody, that you can, get a significant clinical response along with biologic responses.

For instance, this FcRn receptor blocker is supposed to drop autoantibody levels, and it did. Okay? And the same was seen with the dual B cell inhibitor enalumab. So if you can show clinical benefit in a phase three trial, that's what we want to see. That's what we need.

How they're going to be used in practice remains to be seen. So I want to remind you last week, this week, and the next two weeks, we're going to have replays from RoomNowLive twenty twenty five, that was in February. Last week was on psoriatic arthritis, next week is on spondylitis, and the last week is going to be on vasculitis. You may want to see these excerpted talks. I think that they're instructive, and tell you the quality of what you'll see at RheumNow Live in 2026.

It's coming. You can register now. Go to roomnow.live, the meeting is February in Dallas, you can be there virtually if you like. We've got look at the agenda, our speakers are fabulous, Tahina Nioji is talking about disease modification in osteoarthritis, Susan Goodman is going be talking about perioperative management of RA patients and use of immunosuppressive therapy. Rohit Agarwal is talking about two talks on myositis.

Again, look at the agenda, you'll want to be there, I want to be there, I have to be there. We'll see you next week, bye.