Prophylaxis Against PJP in SLE: I'll Pass Save

Hi everybody. It’s Mike Putman. I'm an assistant professor of medicine at the Medical College of Wisconsin in Milwaukee, Wisconsin, and I am here talking to you with RheumNow about my favorite, least favorite topic, which is PJP prophylaxis.

So I think we're all somewhat familiar with PJP prophylaxis. This is the thing we do to stop the scary infection. The scary infection in particular: PJP is pneumocystic JCI pneumonia. This is an opportunistic infection that affects people who are immunocompromised. Now, this is a scary thing, and I'm going to start by actually steelmanning the case for doing PJP prophylaxis before I explain why I think you probably shouldn't be doing too much of it.

PJP was actually discovered by Chagas - we all well know of Chagas - and mistaken initially as a trypanosoma. It rose to prominence, though, in the 1980s during the HIV epidemic where it was a leading cause of death among folks who had HIV and low CD4 counts.

Now, around that time, we said, hey, I mean, this is a horrible infection and we know these people have low CD4 counts. What if we give them something to prevent this horrible, horrible complication? And so that's where we started giving them prophylaxis against PJP, specifically with Bactrim, but pentamidine and atovaquone and dapsone are all options as well. Now, what we discovered is that taking a little Bactrim, maybe even three times a week, is highly, highly effective at preventing PJP infections. This saves a lot of lives.

We said this is a great idea for folks who have HIV and low CD4 counts, what if our patients with transplant who keep getting weird pneumonias are also getting PJP? Lo and behold, it turns out that folks who are getting - especially hematologic transplants and who are getting horrible bone marrow induction regimens and things of that nature - seem to be developing PJP as well. So the malignancy doctors said, hey, why don't we try this PJP prophylaxis thing? Maybe we'll save some lives as well. It was highly effective in that area and likely saved a lot of lives.

And so this is kind of the way medicine works. We start with a thing, it's a great idea in one place, we just kind of roll it out and roll it out, and it sort of snowball rolls down the hill, right?

In the past 20 to 30 years, many rheumatologists have been giving PJP prophylaxis for patients with lupus. Up to a third of patients in observational dataset with lupus, who are initiating therapy with cyclophosphamide and high dose steroids, are getting PJP prophylaxis.

Now, that seems like a reasonable thing to do, but here I'm actually here today to argue that most patients with lupus should not be receiving Bactrim or related drugs.

Here's why.

Now, the most important reason is that PJP is surprisingly rare among patients with lupus. Now, we think the rates in people with low CD4 counts and HIV are reasonably high, high enough that it was an epidemic of this.

But in lupus, it doesn't happen so much.

Now, the first paper that keyed me into this was a 2019 publication by Jinoos Yazdany’s group. They followed 316 patients. There were no cases over 640 person years of follow-up, zero PJP  in this group. Now, I actually looked into this using some electronic medical records data. We looked at 6,000 patients with lupus. We saw only five cases of possible PJP. That's an instance of two cases per thousand person years. So if you treat a thousand patients with lupus for a year, you might see two cases of PJP.

And the problem with that, is a lot of those cases aren't real. A lot of times someone was giving the diagnosis code for PJP, but the patient actually didn't have PJP. We're looking at some of the VA data that we found is that something like 20% of the cases who got a diagnosis code for PJP actually had any proof of having it. So it's actually quite rare to see this in lupus.

Now, the second reason to be hesitant is that this is surprisingly harmful. In the paper I mentioned by Dr. Yazdany, one in 50 people had an adverse event. In my data, we saw significantly higher rates of hematologic abnormalities, kidney issues, and there have been a bunch of studies that recapitulated this sort of across the world: low rates of PJP and a relatively surprisingly high rate of adverse events.

Now, the third reason that I think we probably shouldn't be doing this very much is that we’re giving less and less steroids. So patients with lupus used to be getting very, very large quantities. The most recent guidelines actually recommend 40 milligrams per day or lower. And if you're tapering that down relatively quickly, you'll be to under 20 milligrams within four weeks or so. Patients are just not spending nearly as much time at that risk level as they once were. And so I think that the risk of PJP is probably going to be going down over time. This is also true where cyclophosphamide seems to be a big offender. MMF not quite as much, and that's sort of the backbone for lupus management today.

Now the last thing that I want to mention, and this is something I've been thinking about a lot lately, is that patients with lupus are just getting so, so many pills.

We're talking about a patient with new onset lupus nephritis. They're starting prednisone. That's two tabs of pred 20 milligram daily, and then they're getting four to six tabs of mycophenolate, a brand new chemotherapeutic medication for them. For most people who have any proteinuria, the new guidelines recommend getting that person on an ARB. So you're on a couple tabs of low statin or Valsartan or something along those lines. All patients with lupus should be on hydroxychloroquine. So if you're not a small person, you're probably going to be on two tabs of hydroxychloroquine daily. Most rheumatologists - I've also posted this, well, that's a different conversation - most rheumatologists are giving calcium and vitamin D supplementation.

That is 14 pills per day that the patient with new lupus nephritis has to take.

That is not even counting belimumab or voclosporin or one of these other things that the guidelines also recommend you be giving them.

And so on top of this enormous burden of pills, we're also going to throw Bactrim into the mix, which is a drug that notoriously interacts with all sorts of different systems? It's notoriously problematic in lupus and may cause issues with your kidneys.

It is a kind of thing that, if you were to rank the stuff that's important in management of lupus, I think PJP prophylaxis is very low on that list and might actively be harmful.

As always, there's some caveats.

Now, I didn't say that nobody with lupus gets PJP. There will be patients with lupus who get PJP, but I think that you can at least make some efforts to decide and be a little more judicious in your use of it. Now, in a lot of the studies that I've done looking at PJP, we noticed that the folks who get PJP are the ones with structural lung disease. So if they have interstitial lung disease, we see this in ANCA associated vasculitis, a lot of those people have pulmonary nodules, they've had diffuse alveolar hemorrhage, they have capillary damage. If you're someone whose lungs are heavily affected, I'm actually probably going to give you a little bit of PJP prophylaxis - Bacrtim Monday, whether or Friday or one of the other options - depending on the patient and the other medications that they're taking.

But there is a subset of people who are really sick. Say they had CNS Lupus and then you expect them to be on a higher dose of steroid for longer. Say they have had infections. If you have already had infections, that's a sign that this person is predisposed to having infections. I would consider it in that patient and someone with structural lung disease, I would consider PJP prophylaxis. I would say that 39% what we saw in Dr. Yazdany’s cohort, 33%, what we've seen, a lot of the other ones, is way too high - far too many people getting Bactrim or in a related drug. Zero percent is probably too low.

So somewhere in the middle is where I would recommend you land as a practicing rheumatologist. Hope that was helpful. Thank you for tuning in. Be sure to find all of our other coverage of lupus at RheumNow.com