Systemic Effect Prevention: Evaluation & Dose Modification
EP: 1.Spinal Muscular Atrophy (SMA) Overview
EP: 2.Typical SMA Presentation Upon Diagnosis
EP: 3.Sebastian's Story: Initial SMA Symptoms and Assessment
EP: 4.Spinal Muscular Atrophy Diagnostic Workup
EP: 5.The Importance of Treating SMA Early
EP: 6.Treatment Barriers: Cost, Location, and Delivery
EP: 7.Treating Children and Spinal Tap Risks
EP: 8.Systemic Effect Prevention: Evaluation & Dose Modification
EP: 9.Life During Therapy: Good Days and Bad Days
EP: 10.Multidisciplinary Management and Educational Support
EP: 11.Family Planning for People With SMA
EP: 12.Centers of Excellence and Future Oral Medication
EP: 13.Psychological Effects of SMA on Children and Adults
EP: 14.The Impact of the ENDEAR Trial Regimen
EP: 15.Ongoing Clinical Trials & Managing Patient Expectations
EP: 16.Adopting Neuromuscular Therapies for SMA
Philippa Cheetham, MBChB, MRCS, MD, FRCS: Now these medications are going into the spinal canal. Are there systemic effects that may have effects on liver function, kidney function, or general immune function that patients need to be aware of?
Crystal Proud, MD: Spinraza has some FDA recommended analyses that should be performed prior to using it for treatment, and then with each successive infusion of medication. We perform blood and urine tests. We check a complete blood count, a PT [prothrombin time], a PTT [partial thromboplastin time], and a urine quantitative protein. Some of those recommended evaluations are because Spinraza is considered what’s called an antisense oligonucleotide, an ASO. And there are other medications that are ASOs that have been demonstrated to have certain adverse effects. And so as a class result from ASOs, the FDA has recommended that we check those things. We do that routinely for our patients. I personally have not had any patient who has had any of those adverse effects, but we continue to follow FDA guidelines and check those.
Philippa Cheetham, MBChB, MRCS, MD, FRCS: Sebastian, when you first heard about this treatment, did you think that these infusions were just going to be a one-off and you'd be much better? Were you aware that it was going to be an ongoing process where you'd be having these top-up infusions?
Sebastian Mills: Yes, Dr Proud did explain how the maintenance and all of the loading actually works. Of course, with anything, your body has to adjust to it. So, the 2-week trials, and then you go from the month to the 4 months; she did explain that to me very well. I did understand this will be an ongoing process, but I also understood that through this ongoing process, you won't see stuff overnight. With the testing that usually occurs after all of my shots, I'm able to see whether stuff has gone up or it's at an average level now or if it's staying in a consistent basis.
Philippa Cheetham, MBChB, MRCS, MD, FRCS: One thing that I really wanted to clarify, when you see a patient upfront with spinal muscular atrophy, and you’re planning treatment, do you modify the frequency of these infusions based on response? Or do you have a set protocol where you want to say, “Look, we’re going to give infusions at this time, this time, this time, this time, regardless of whether you have a good response or not. And then at the end, we'll evaluate.” How much does the patient response throughout treatment dictate the frequency and the number of infusions that you're going to give?
Crystal Proud, MD: There is a set routine, a set frequency that is in the prescribing information, so I am not permitted to move it forward or backward. It is set at every 4 months and maintenance. However, there is the discussion that goes into the planning phase, which I think you're referring to. That discussion becomes much different with a patient who, in the past, would have been labeled a type 3, like Sebastian.
When we see our type 1 and 2 babies who are declining in front of our eyes quite rapidly, their response to treatment can be very readily visible within the first few months. Our patients who are older and who walk, like Sebastian, we know are already starting with a higher baseline number of motor nerves that are present and that we may not see as dramatic of a response as rapidly as some of those younger children, but we do still see a response. It just may be that we need a longer commitment to be able to observe and quantify that.
And so, I ask my patients up front that I would really like a commitment if we are going to move forward with this treatment together. I want a commitment that we're going to pursue this and really obtain some objective data before hearing someone say, “I don't think it's doing anything for me, doctor.” Usually, I ask for somewhere around 1 or 2 years to be able to look at scores, look at tolerability, look at comfort level and see whether we've achieved something that's desirable to the patient. And I've not had anyone come off of treatment after that period.
