0:03
Hello everyone. This is Bella Mata from RheumNow reporting live from ACR 2026 and I have with me Shivani Garg, who's an amazing researcher, and we're going to talk about a study that was one of the most downloaded studies today.
0:20
It was a poster, but talking about something that I think is very important: what do we do with hydroxychloroquine dosage.
0:27
So can you tell me what was your study and why do you think it's important and what's the takeaway?
0:34
Yeah, great. Thank you for having me. So we have — all my clinician colleagues have all been there, you have been there, I've been
0:42
there — we have an email from our ophthalmologist saying, "Oh, the dose is more than 5 milligrams per kilogram for hydroxychloroquine that we use
0:51
for almost all patients with lupus."
0:53
So what to do now? Is it safe? Like, where is this threshold coming from?
1:00
But there is also evidence and data that has been published recently that having the dose below or at 5 mg per kilogram per day is also associated with a six-fold higher risk of having a lupus flare that can put a patient in the hospital.
1:16
So you're saying that we are underdosing some patients. Yes.
1:20
So it's not clear whether this is the threshold which is safe and effective.
1:26
So we wanted to have a closer look with more patient data.
1:31
What we did was a meta-analysis — it's an individual patient data meta-analysis — that pulls data from different cohorts including SLICC, which is an international cohort, the Wisconsin cohort, Mass Brigham, and Kaiser Permanente cohort.
1:47
And these are all lupus patients, and they have a minimum exposure of five years to hydroxychloroquine, just because we know that early on it's cumulative toxicity.
2:00
So we made sure that all patients had at least — the patient count was around 2,533.
2:06
So it's around 2,500 patients, so it's a large sample size.
2:12
So what we did was that for some datasets such as Mass Brigham and Kaiser Permanente — which was with the help of my collaborator
2:22
and co-author on this paper, Dr. April Jorge — we had log hazards ratios with every 0.01 mg per kilogram per day dose increase, meaning
2:34
we had time-to-hazard, or risk of having toxicity.
2:39
And then from other cohorts we had line-level data, so we converted it into the same log hazards ratio so that we could pool the data together.
2:48
And what did you conclude? So when we pooled all hazards ratios together, we did a linear and nonlinear linearity trend analysis.
2:59
What it means is that we put a threshold — we set the threshold or cutoff at 4, 5, 6, and 6.5, which was the old threshold for hydroxychloroquine safety.
3:10
We noted that it's a linear association.
3:13
There is no clear cutoff when it comes to hydroxychloroquine safe dosing.
3:18
So like in everything, right — instead of having a hard line in the sand, there's a threshold or a curve.
3:25
So it was not a curve, it was a straight line.
3:28
What it means to our clinician colleagues is that if you dose a patient at 6.5 mg per kilogram, they reach a toxicity risk of 4% in 20 years.
3:54
For people who are dosed at 5 mg, they will reach the same toxicity in 22 years.
3:55
So that's the difference. It's not that there is a safe threshold where all toxicity lies above 5 mg per kilogram and no toxicity below — it just means that it is the cumulative exposure.
4:00
So all you're saying is: don't go crazy with the 5 mg per kilogram line.
4:07
If you need to give a little more, you'd rather err on the side of that — all it'll change is the risk of toxicity decades down the line.
4:15
Exactly. And you'd rather dose it well than underdose it.
4:18
Is that what I took away? Exactly. But personalize it, because there are patients — and we know that lupus patients tend to flare early on — so in the first five years, if it is difficult-to-control lupus and they have some flares or residual symptoms, you might want to increase the dose up front.
4:41
And the ACR guidelines allow that — to tailor based on the activity of lupus — and then once they are stable, you can, with close monitoring, bring down the dose toward the threshold so that they can take it longer.
4:54
Great. So I think that's something that we need to take away and also educate our ophthalmology colleagues with, because that's the panic email that you were starting to talk about.
5:08
So I guess — is there a threshold that you're probably okay with, dose-wise?
5:19
A lot of times what I do is use the threshold as a guide, particularly when my patients are stable.
5:25
Then I might want to get them down a little toward the threshold so that they can take it longer, because the data for hydroxychloroquine is not just about controlling lupus — it is about preventing damage and survival.
5:37
So with that data, I want them to take it longer until the time they don't need it.
5:41
And I also add a layer of hydroxychloroquine blood level monitoring.
5:49
Yeah, that's another thing that we as clinicians need to start thinking about and doing.
5:55
So this is very helpful and very useful for clinicians.
5:59
I think my key takeaway is: don't be scared of the 5 milligram per kilogram threshold — go hard up front.
6:06
And your data is a very thorough, well-done study showing that.
6:13
So with that, thank you so much for joining, and thank you for listening. For more, just follow us on RheumNow.
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