Here's a handy synopsis of a “hands-on” review of the current state of monitoring disease and treatment decision making in patients with multiple sclerosis.
You can tell it is the last day of a conference when most of the few people who remain are attending with their suitcase in tow. This morning, I attended the MRI in Multiple Sclerosis (MS) course, hosted by Robert Bermel, MD, from the Cleveland Clinic and Robert Naismith, MD, from Washington University in St Louis. These physicians provided a “hands-on” review of the current state of monitoring disease and treatment decision making in patients with MS.
The main topics included NEDA (no evidence of disease activity) and an approach to treatment given today’s multiple options.
In MS, NEDA can be defined in at least 2 different ways-clinically and radiologically. But why define NEDA radiologically? Because MS studies have shown that MRI is more sensitive to disease activity than to clinical symptoms and is a good objective measure of the patient’s response to treatment.
Is clinical improvement or stabilization in disease course sufficient? Unfortunately, MS studies have shown that the answer is no. A 2009 study by Prosperini and colleagues1 of patients receiving interferon-beta (IFNB) therapy showed this. MRI done at 1 year after initiation of IFNB therapy was correlated to disability at 5 years. Clinical status of the patient did not matter during that first year, but if two or more additional T2 lesions were found, then there was a greater than 50% chance of increased disability. Disability was defined as persistent loss of more than 1 point on the Kurtzke EDSS (expanded disability status scale).
The MRI predicted the patient’s outcome. This is something to think about when reviewing follow up MRI studies on patients with MS.
In 2013, Dr Bermel2 confirmed and expanded this. He showed that if you look at the activity of disease at years 1 and 2 of treatment with IFNB, and then follow patients for 15 years, those with active disease at years 1 or 2 were more likely to be in the top quartile of patients with worst EDSS progression (ie, more disability). In his study, evidence of disease was defined as 2 or more new gadolinium-enhancing lesions at 1 or 2 years after starting IFNB, 3 or more new T2 lesions at 2 years after starting IFNB, or 2 or more clinical relapses in the first 2 years of treatment.
Although no data have been published for some of the other therapies in MS, I wouldn’t be surprised if the findings are similar.
Continuing MS disease
This leads me into the topic of how to handle patients with continuing MS disease. Although we have a lot more alternative disease modifying therapy (DMT) today, it is still very possible that at some point you are going to feel like you’ve used up all your options.
What should you use to determine when treatment should be added or changed? Do you rely on the MRI? The patient? Both? The Bermel study can provide some guidance for those being treated with IFNB-but what if they are receiving other DMT? How often should the MRI be done? When do you decide that they have tried a DMT adequately to determine its effectiveness?
Although there are no hard and fast rules, suggestions were presented by the speakers.
Dr Naismith, presented a scale that he has been working on that looks at a combination of demographics, disease characteristics, and imaging results to “rate” a patient’s disease severity as mild, moderate, or severe. He also divided DMT into 2 groups-“standard” or “enhanced”-based on their efficacy. The enhanced efficacy medications included natalizumab, fingolimod, and alemtuzumab. He presented 3 sample cases and rated them. An example of a severe case was that of a young African American man with active clinical disease, poor recovery from his prior symptoms, and active lesions on MRI. He would be a candidate for the enhanced-therapy group of DMT.
Although Dr Naismith still needs to confirm his scale, it provides a framework for looking at the disease and DMT therapy. He also presented Dr Freedman’s2013 updated scale of “treatment optimization recommendations”3 model as another way to think about when should we change therapy in the MS patients.
Monitoring MS patients
Naismith and Bermel concluded by discussing how to monitor MS patients. The decision to change therapy should be influenced by several factors (as noted above): following a standard protocol of monitoring was recommended. After a DMT is started, a 3 month follow-up visit to review patient’s tolerance and initial response was suggested.
Obtaining a “re-baseline” MRI at 6 months was proposed-earlier if needed, or later if disease is milder or if the patient is taking a DMT that takes longer to be fully effective, such as glatiramer acetate. At 6 months, you would have a good idea of the effectiveness of most DMTs on individual patients. Surveillance MRI studies were recommended once a year for the first 2 to 4 years until you have a sense of the patient’s overall disease activity, at which time you would begin to extend the timing between studies if the patient is stable or you would change therapy and begin this process again.
1. Prosperini L, Gallo V, Petsas N, et al. One-year MRI scan predicts clinical response to interferon beta in multiple sclerosis.Eur J Neurol.2009;16:1202-1209.
2. Bermel RA, You X, Foulds P, et al. Predictors of long-term outcome in multiple sclerosis patients treated with interferon beta. Ann Neurol. 2013;73:95-103.
3. Freedman MS, Selchen D, Arnold DL, et al. Treatment optimization in MS: Canadian MS Working Group updated recommendations. Can J Neurol Sci. 2013;40:307-323.