Jeffrey M. Kaplan, MD: You brought up a really good point. If we diagnose somebody with primary-progressive disease very early on, at a young age, I think ocrelizumab has a much better chance of being effective than in our patients who have carried that diagnosis for many years, for which we have tried other medications that obviously may be not be FDA (United States Food and Drug Administration) approved—things such as methotrexate or Imuran [azathioprine]—and we were seeing minimal or no effects.
And so, when I have had patients who have had primary-progressive disease for 10 years, 15 years, 20 years, and then when I switched them to ocrelizumab, the odds of the drug helping those patients have been relatively low. And also, I have had some of those patients, unfortunately, develop some pretty serious infections. These people have comorbidities. They have diabetes. They have hypertension. They have obesity. These patients have been ill with primary-progressive multiple sclerosis for many, many years with no effective treatment.
Did you notice any rise in infection rates in your patients you placed on ocrelizumab [who] are primary-progressive?
Matthew J. Baker, MD: Well, it seemed to correlate with disability status scales. If someone had long duration, primary-progressive, higher EDSS [Expanded Disability Status Scale], there’s a fine line you walk between following what was done in clinical trials that led to approval of the drug, and then, after post marketing, post approval, use of the medication. So, yes, I would say in those patients that I used it on and who are older, who had more severe disease, there was a tendency toward increased infection rates, overall.
Most of those are treatable and are not serious. I do follow immunoglobulin levels in that setting, too. There seems to be an association between lower immunoglobulin levels with longer duration of therapy and increased risk of urinary tract infections, particularly, which are common in our patients with more advanced multiple sclerosis, as well.
Jeffrey M. Kaplan, MD: I’m really glad you brought that up, because that is also kind of a segue into my next question to you. But I’m going to say 1 more statement before I segue. I have been checking levels on my patients [with multiple sclerosis] for several years, and I definitely had a significant reservation about placing patients on B-cell depletors who had low IgG levels or had IgG1 and IgG3, or IgG2 and IgG4 deficiencies on their subsets. I think that’s really crucial.