Myasthenia Gravis Learning Zone
Transcript: Complex comorbidities
Professor Francesco Sacca
Interview recorded June 2024. All transcripts are created from interview footage and directly reflect the content of the interview at the time. The content is that of the speaker and is not adjusted by Medthority.
Good morning, and welcome on this case presented on Medthority regarding a patient with myasthenia gravis and complex comorbidities. My name is Francesco Sacca, and I am associate professor of neurology at the Federico II University of Naples, Italy.
I would like to start by explaining this clinical case because this is a case of a 79-year-old female with generalised myasthenia gravis. And it is a patient with eight years of history of myasthenia gravis since diagnosis. And what makes this patient special, or let's say different, from other patients is that, first of all, she's in one of the oldest patients we have. We have patients older than this one of course, but it is one of what we now call late onset myasthenia gravis patients. And this category here has increased in size a lot during the past years. So we were used to diagnose myasthenia gravis in younger females and older males, but this part, this, let's say subgroup of patients with late onset myasthenia gravis or even very late onset myasthenia gravis has increased a lot during the past years, and this is a very typical case.
So onset at the age of 71, several comorbidities that, of course, limit new treatments and limit the use of standard of care, so what we would call prednisone and immunosuppressants. So getting into the details of this history. So eight years since diagnosis, as we said, treated with thymectomy and acetylcholine receptor positive patient and MuSK negative patient. Prior and concomitant generalised myasthenia gravis medications include pyridostigmine that was increased up to the maximum tolerated dose, prednisone, which was also increased to what we would already call a very high dose, especially considering the age of this patient. She was also treated with azathioprine up to 100 milligrammes per day, which in many patients is already a fairly high dose. And also underwent treatment with IVIg and PLEX as part of what we would call a standard of care.
So all these treatments together kind of represent what we've been using in Italy, probably in Europe, and many other countries as a standard of care for myasthenia gravis patients, including IVIg or PLEX, which could be considered either as rescue treatments or as what in many other guidelines are called early-fast acting treatments or those treatments that had a very quick onset and are used when patients do not respond adequately to corticosteroids or nonsteroidal immunosuppressants. And in her medical history, you could see that she developed a Cushing's syndrome quite early. She has hypertension and she has also a sleep apnoea syndrome.
And there's something else in the medical history which is not appear, but she's an older patient. And with older patients, we'll see that there are some caveats here looking at the MG-ADL and how well patients improve after treatment with innovative treatments. So going to her history, as you can see here, she developed, in 2014, the first symptoms of myasthenia gravis. Those were diplopia and limb weakness. They both appeared at the same time, so wouldn't really call it an ocular onset, it was already a generalised onset. And she initiated pyridostigmine and prednisone straight away. Then after that, azathioprine.
This was kind of a standard in Italy until a couple of years ago. We usually started with prednisone alone and then started an immunosuppressant. This is not the case anymore, we now tend to use immunosuppressants quite early in the disease course just to avoid taking too much time to taper down steroids.
And after initiating azathioprine, the patient didn't really have an excellent response to azathioprine, and for this reason, we started IVIg in 2016. But again, response was really not excellent, so we gave up with IVIg.
And what about her comorbidity? So not only did she have a sleep apnoea syndrome, she also developed osteoporosis quite early, probably because of the treatment with corticosteroids at a high dose, probably because of her age, and she also has COPD. In 2020 she developed hepatotoxicity, and then later on Cushing's syndrome. And for this reason, we suspended azathioprine and also think about reducing prednisone dose. This is her baseline assessment.
I wanna take some time here because she has an MG-ADL score of 13, which is already quite a high score. But if you closely look at her MG-ADL at baseline, she has some ocular symptoms, of course, she has an eyelid drooping which is constant, so she has a score of 3. She has double vision, but the other items where her score is quite high and a score of 3, is impairment for the ability to arise from a chair, so lower limb impairment. And this is very frequent, of course, in myasthenia gravis patients. But also let's keep in mind that she is an older patient. So in older patients, lower limb weakness is kind of very frequent, so sometimes independent of myasthenia gravis. She also has a score of 2 in her upper limbs and a score of 1 in all remaining scores. So, the total is 13 at the MG-ADL, but even her QMG score is very high, she has a score of 18. And I don't have the single items here, but they kind of follow quite closely the MG-ADL items with higher scores in her lower limbs compared to her upper limbs, and eyelid droop as shown here in the MG-ADL.
So what happened to the patient once we started treating her? So we went for a first cycle with efgartigimod. Why efgartigimod? Well, of course, it's a patient that is non-respondent to standard of care. It makes it very complicated for this patient to go through another nonsteroidal immunosuppressant, probably even useless. So when we didn't have such innovative treatments, we used to start, again, with another immunosuppressant, but in this case, it doesn't really matter a lot. So we started with efgartigimod and had an excellent response despite having a very long history of myasthenia gravis being an older patient. And as you can see the MG-ADL went from 13 to 4 quite quickly during the first treatment cycle.
We then waited a little bit and waited until the patient started deteriorating again, and then reinfused efgartigimod. And as you can see here, we still have a very good response at the second treatment cycle. Despite not reaching very low scores after that, there is something very interesting here. So when we start treating younger patients with a very short disease duration, our aim is usually to get to the minimal symptom expression. So those scores of MG-ADL of 0 or 1, or even minimal manifestations. This is a patient that clearly doesn't get there, but still has a very good improvement.
So going from 13 down to 4 or 5 after the first and after the second treatment cycle with efgartigimod. And you can see that the QMG score also goes from 18 to 13, then from 16 to 12, meaning that this is a very good response even if you consider the very short interval here.
So what is important in this case that with older patients, with patients that have comorbidities, with those patients that might already have a lower limb impairment, that might have a chronic myopathy because of steroid use, you will not be able to achieve a minimal symptom expression.
But this doesn't mean that a treatment like efgartigimod is not effective because when we, all of us, as physicians, advertise innovative treatments as excellent treatments that are able to get to the minimal symptom expression and let's say 30, 40, even more percent of our treated patients, we might think that those patients not reaching a minimal symptom expressions are not responding.
But we have to keep in mind that with older patients, the minimal symptom expression is sometimes not a realistic goal of new therapies including efgartigimod. And for a patient like ours, getting all of these scores of 3 of the MG-ADL down to 2 or down to 1 means a lot. So 13 to 4 to 5 of the MG-ADL is an excellent response, and probably is the highest improvement that we can achieve in these patients.
Thank you very much for your attention.
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