Freddy Caldera, DO, on Measles Among Patients With IBD

Measles Protection in IBD: MMR History Preferred Over Commercial Serology

• Measles, U.S.: >2,300 cases by July 23; >762 cases occurred in the prior Texas outbreak, linked to unvaccinated school-age children.
• IBD on advanced therapy: Adult and pediatric studies found sensitive laboratory testing superior to commercial assays; adult commercial measles antibody testing had 29% negative predictive value.
• Clinical practice: AGA/ACG guidance advises against serology to determine measles protection. Confirm 2-dose MMR vaccination, vaccinate household members, and coordinate with infectious disease/consider IVIG if an IBD patient develops measles.

Thanks for tuning in. My name is Dr. Freddy Caldera. I'm a professor of medicine at University of Wisconsin. I'm a physician scientist with interest in safety of medications and IBD with a special interest in health maintenance. And today I'm going to be talking to you about measles, something that many physicians and advanced practice providers have learned about in their training, or school, mostly in textbooks, but we haven't seen clinically. Regretfully, we are dealing with one of the largest outbreaks, and as of July 23rd, the U.S had more than 2300 cases of measles this year. We're only 7 months in, and we already surpassed 2025, making it the worst year since 1991.

And I'll tell you some of the work we've done. But what really prompted this was the large outbreak that occurred last year in Texas, where there were more than 762 cases prompted from unvaccinated kids, school-age children that spread measles. And this led to a lot of colleagues reaching out to me and saying, what should we be doing with our patients with IBD, especially those on advanced therapy? Because as you may be aware, the MMR—measles, mumps, rubella vaccine—is a live vaccine. It's typically given during childhood at 12 months and 4 to 6 years of age. Prior to the pandemic, there was a really high uptake of the vaccine, greater than 95% in children going to school. But due to falling rates in certain groups, there's been these measles outbreaks that have been imported into the U.S.

And that prompted us to really do some work, because we wanted to really look at how reliable a commercial assay is to determine are you protected or not. In both the AGA clinical practice update and ACG preventative guidelines, we have discussed that you shouldn't be using serology to do this. So we did a couple of things. One, we published a statement in CGH on guidance of dealing with measles and talked about what defines being immune to measles, either getting an MMR. We provided some guidance of how long you would have to wait if you were going to provide a live vaccine, which is not a situation that happens commonly.

But what was really important is both at DDW, we presented 2 abstracts that have now been published in CGH and the Red Journal. One was a study in adult patients with IBD who were on advanced therapy and we knew were protected. These were patients who had consented to future studies. And we measured their seroprotection in the lab and then used a commercial assay to see, you know, could we determine seroprotection and found that the commercial assay was inferior to the more sensitive test we did in the lab, and the commercial assay had a negative predictive value of 29%.

So sit with that for a second, that if a measles antibody test comes back negative on someone with advanced therapy, which could happen about 7 times in 10, this could really be a big deal for a patient. You could be in a serious conversation of asking someone, well, do you want to stop your therapy to get another booster? Now this patient may be concerned about outbreaks and change their behavior because they may feel they're susceptible. So this has a very big deal for the patient.

We found the same kind of findings in the different cohort of pediatric patients with IBD, where again, we found that the more sensitive ELISA we did in the lab was superior to the commercial assay. And why assays? So commercial assays were developed in the time where measles was endemic, and the goal of this ELISA was to detect infection. They were never meant to detect the antibodies in someone who was vaccinated. We know that antibodies are higher after an infection than vaccination. It doesn't mean that lower antibodies are associated with a lack of protection, because the immune system has many robust ways, whether memory B cells, to protect that patient who's been vaccinated. So the moral of the story is don't rely on a commercial ELISA to determine if someone's not protected.

Prior to the pandemic, most adults had received their MMR series. So making sure that someone's received an MMR vaccine is something that's very doable. One additional abstract and some work we did because of the measles outbreak is—we presented this at DDW also— we asked patients who we knew had received the MMR series and wanted to see if their self-report was reliable. And we found them stating that they were very confident that they had gotten an MMR vaccine series was very sensitive. So patients knew if they had gotten their MMR series.

So what can you start doing in clinic? Regretfully, these outbreaks will still be occurring throughout the U.S. due to unvaccinated cohorts. So if you're in whatever state next you have outbreaks where these outbreaks have occurred in Utah, if you start getting calls from your patients asking should they be getting a titer or serology checked, to determine if they're protected, you should tell them no. Both AGA clinical practice update and ACG preventative guidelines don't recommend this due to the fact that these assays are not sensitive and have a high negative predictive value.

So now that you heard about that the serology or these titers aren't accurate, what can you start doing? Regretfully, outbreaks have been occurring in Texas, South Carolina, Utah. So these may be occurring next. There are a lot of things that you can start doing. So preemptively educate your staff that these serologies are not accurate, and if they start getting calls or portal messages from patients, that this is not something that we recommend. Making sure that you're assuring that your patients prior to starting advanced therapy or those that are not advanced therapy are up to date and receive 2 doses of their MMR vaccine is something else you can start doing.

Additionally, making sure that their family members are vaccinated. So someone with advanced therapy. has young kids make sure that they're getting up to date and anyone in their household is getting vaccinated to make sure you're getting a cocoon immunization strategy.  Something where we have less data is is if you have a patient with IBD who develops measles, regretfully we don't know what could occur in those situations just because measles had been eliminated prior to these advanced therapies. So we don't know much. In the CGH guidance, we talked about coordinating with infectious disease, about considering using IVIG regardless of their vaccination history. But this is something where you've got to be working closely with your ID specialist to know what else needs to be done.

I think, reassuringly, the last thing you can do is if an epidemic or outbreaks occur in your region, it's just reassuring patients that they're not going back to COVID where they're now more at risk. The purpose of our research was to show that these assays weren't accurate so that people can feel secure and feel protected. Because we wouldn't want someone to get in a situation where now they have a test that tells them they're not protected and now that changes their behavior.

So I appreciate your time. Thank you very much.