Click here to watch Dr. Virginia Devonshire discuss the case and your responses to the quick poll.
Michael P. is a 55-year-old male diagnosed with relapsing MS five years ago. He presented with a spinal cord relapse that resulted in residual sensory and mild bladder dysfunction in his lower limbs and EDSS 2.5. His MRI had a thoracic lesion and more than 10 brain lesions meeting McDonald 2017 criteria. He was started on teriflunomide 14 mg/day but reported poor tolerability.
Within two years, Michael had a second relapse and had accumulated further disability with motor weakness, and worsened bladder and sexual function. His MRI showed a new thoracic lesion. His EDSS was 4.0. He was started on oral cladribine. Baseline CBC with differential was normal, and serum IgG was 7.0 g/L (normal range 7-16 g/L). He tolerated treatment well and completed his two courses. A re-baseline MRI at 20 months showed no new lesions. In Year 3, the MRI revealed a new 3-mm periventricular lesion, a 4-mm pontine lesion, and a 10-mm Gd-enhancing lesion in the frontal lobe. Michael reported increased balance problems. His EDSS remained 4.0. His lymphocyte count is 1.1 x109/L with normal neutrophils. Serum IgG is unchanged at 7.0 g/L. He is otherwise well and healthy.
The survey is now closed. There were 39 responses. See below for a summary of the answers you provided.
Question 1: Is this a treatment failure? Would you consider another course of cladribine?
A majority of respondents (85%) agreed that this is a treatment failure and that treatment with a higher-efficacy DMT was warranted. Two percent said it was treatment failure but would prefer switching to a moderate-efficacy DMT. Eight percent considered this to be a suboptimal response and they would try another two-year course of cladribine, and 5% said they would consider cladribine only after further discussion with the patient.
Question 2: Could a modest-efficacy therapy be considered since only MRI breakthrough was seen?
A total of 92% of respondents said a higher-efficacy DMT is needed since the patient is having worsening symptoms and disability, or to reduce the lesion burden and slow disability worsening. Another 5% would consider a moderate-efficacy DMT since the breakthrough disease activity with teriflunomide may have been due to poor adherence. Another 3% said a low- or moderate-efficacy DMT would be expected to be as effective as a higher-efficacy DMT in this older patient.
Question 3: Would you consider starting an anti-CD20 given his age is 58?
Two-thirds of respondents said they would start an anti-CD20 agent to reduce ongoing disease activity, and one-third would initiate an anti-CD20 therapy to slow disability worsening. No respondent thought that the benefit-risk of anti-CD20 therapy was unfavourable in an older patient.
Question 4: If you considered an anti-CD20 agent, would an IgG in the lower range of normal influence your treatment selection?
A small majority said that the patient’s IgG level would influence their treatment choice, with 49% opting for ofatumumab and 5% for rituximab. About 23% said they were unsure about the impact of treatment on IgG and would start treatment with whichever anti-CD20 agent the patient preferred, and 5% said that IgG would be expected to remain >LLN in most patients. Another 18% said that a low IgG is not strongly associated with infection risk.
Question 5: If placed on an anti-CD20 agent, what would the long-term plan be?
In the absence of clear evidence on the optimal approach to de-escalation/discontinuation, opinions were divided among the respondents. A total of 41% said they would treat for 2-3 years then gradually de-escalate using an extended-dosing regimen. Similarly, 23% said they would maintain treatment for 2-3 years and then discuss discontinuation once the patient turned age 60.
Another 28% said they would maintain treatment for as long as the patient showed ongoing clinical worsening and/or disease activity. And 8% said they would treat for a year, de-escalate to a moderate-efficacy DMT for a year, then consider discontinuation if there was little/no disease activity when the patient turned age 60. No respondents opted to start with an extended-dosing regimen for two years before considering treatment discontinuation when the patient was aged 60.
View the video commentary from Dr. Virginia Devonshire.