Are you pro-PIRTs or would you prefer to be maintained? #ResearchSpeak #MSBlog #MSResearch
You may agree, or disagree, that one of the major advantages of the PIRTs (pulsed immune reconstitution therapies) is that they front-load risk with the potential to induce long-term remission and hopefully in some pwMS a potential cure. At present we only have one licensed PIRT, alemtuzumab. The study below confirms what we see clinically, that despite the burden or using alemtuzumab (cost, infusion reactions, secondary infections, monthly monitoring and secondary autoimmunity) pwMS have markedly improved quality of life (QoL) compared to pwMS on interferon-beta-1a.
It is quite remarkable how well pwMS feel post-alemtuzumab. I suspect having an inflammatory soup swishing around in your head, with active MS, makes you feel awful. Switching off inflammation and reducing the inflammatory mediators that drive so called ‘sickness behaviour‘ clearly makes the difference. Sickness behaviour is the clinical syndrome associated with inflammation; i.e. fatigue, sleepiness, low mood, low energy, poor concentration, etc. If you don’t have MS you may relate to how you feel when you have flu or a viral infection; you simply feel awful. From an evolutionary perspective sickness behaviour evolved to force the sick individual to rest and recover from illness. It is clear from this study, and my personal observations, that the interferons are not effective in abrogating sickness behaviour.
Another point that this study addresses is that the clinical effectiveness of alemtuzumab is mirrored by how pwMS feel and unction post-alemtuzumab. Please note improvements were noted in all QoL domains, i.e. physical, mental, and emotional. There are not many DMTs that do this.
Other PIRTS include cladribine, HSCT, mitoxantrone and possibly the anti-CD20 therapies. I suspect that a lot of clinicians will use ocrelizumab in a similar way to how some neurologists are currently using rituximab, i.e. with a 2-year course and then to retreat when disease activity re-emerges. Who knows we may even find a response marker that informs us about the need to retreat with anti-CD20? Now wouldn’t the latter be disruptive?
Arroyo et al. Alemtuzumab improves quality-of-life outcomes compared with subcutaneous interferon beta-1a in patients with active relapsing-remitting multiple sclerosis. Mult Scler. 2016 Nov 24. pii: 1352458516677589.
BACKGROUND: Alemtuzumab was superior on clinical and magnetic resonance imaging (MRI) outcomes versus subcutaneous interferon beta-1a in phase 3 trials in patients with relapsing-remitting multiple sclerosis.
OBJECTIVE: To examine quality-of-life (QoL) outcomes in the alemtuzumab phase 3 trials.
METHODS: Patients who were treatment naive (Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis I [CARE-MS I]) or had an inadequate response to prior therapy (CARE-MS II) received annual courses of alemtuzumab 12 mg/day at baseline (5 days) and Month 12 (3 days) or subcutaneous interferon beta-1a 44 µg three times/week. QoL was measured every 6 or 12 months using Functional Assessment of Multiple Sclerosis (FAMS), European Quality of Life-5 Dimensions (EQ-5D) and its visual analog scale (EQ-VAS), and 36-Item Short-Form Survey (SF-36).
RESULTS: Statistically significant improvements from baseline with alemtuzumab were observed on all three QoL instruments at the earliest post-baseline assessment and sustained through Year 2. Statistically significant greater QoL improvements over subcutaneous interferon beta-1a were seen at all time points in CARE-MS II with FAMS, EQ-VAS and SF-36 physical component summary, and in CARE-MS I with FAMS.
CONCLUSION: Patients treated with alemtuzumab had improvements in physical, mental, and emotional QoL regardless of treatment history. Improvements were significantly greater with alemtuzumab versus subcutaneous interferon beta-1a on both disease-specific and general measures of QoL.
CoI: multiple, Prof G is a co-author on this paper.