ABSTRACT
Aims: ENO Breathe is an online breathing and wellbeing programme for people with Long COVID focusing on breathing re-training using singing techniques. Aim(s): to assess whether ENO Breathe improves health related quality-of-life (HRQoL) in people with persistent breathlessness following COVID-19. Method(s): A parallel-group, single-blind, RCT, comparing ENO Breathe(6 weeks) with usual care in adults, with persisting breathlessness +/- anxiety, following assessment at an NHS Long COVID clinic. Primary Outcome: change in HRQoL using the RAND SF-36 Mental(MHC) and Physical(PHC) Health Composite Scores. Secondary Outcomes: CAT, VAS for breathlessness (rest, walking, stairs, and running), Dysp-12, GAD-7. Participant experience was assessed using focus groups and free-text responses. Result(s): 150 participants (mean(SD) 49(12)years, 81% female, 320(127) days symptomatic;ENO Breathe(n=74), Control(n=76). ENO Breathe was associated with improvement in MHC of 2.42 points (95%CI 0.03 to 4.80, p=0.045), but not PHC 0.6 (-1.33 to 2.52, p=0.541). VAS breathlessness (running) favoured ENO Breathe -10.48(-17.23 to -3.73, p=0.003). Three participant experience themes were identified 1) improvements in symptoms;2) feeling that the programme was complementary to standard care;3) the particular suitability of singing and music to address their needs. Conclusion(s): An online breathing and wellbeing programme can improve the mental component of HRQoL and elements of breathlessness in people with persisting symptoms after COVID-19. Mind-body and music-based approaches, including practical, enjoyable symptom-management techniques may have a role supporting recovery.
ABSTRACT
Background: COVID-19 vaccination induces protective Spike antibodies. Some responses are attenuated in people with multiple sclerosis (MS) on high efficacy disease-modifying therapies (DMT).Whether antibodies afford immunity against emerging SARS-CoV-2 Variants of Concern (VoC) such as Delta and Omicron is unknown. Aim(s): To assess the longevity and breadth of Spike antibody in MS patients after COVID-19 vaccination. Objective(s): To determine seroconversion and antibody binding toVoC Spike. Method(s): Spike antibodies to Clade A SARS-CoV-2 were assessed in 535 MS sera at baseline (n=292), 1 (n=141) and 6 month (n=67) post-second dose, and 1 month post-third dose (n=35), and 489 health worker controls. When known, COVID- 19 vaccines were BNT162b2 (n= 489 controls, n=108 MS patients) and ChAdOx1-S (n=37).Spike antibody binding to VoC Delta and Omicron BA1 was assessed in 68 sera 1 month post-second dose. Demographic and DMT information was available in 269 patients. Result(s): 123/141 sera at 1 month post-second dose, 66/67 at 6 months post-second dose, and 26/35 at 1 month post-third dose were positive for Spike antibodies.Patients who did not seroconvert at 1 and 6 month post-second and 1 month post-third dose (n=28) were treated with ocrelizumab (n=22), cladribine (n=1), fingolimod (n=4), and siponimod (n=1). At 1 month post-second dose, the median and IQR Spike antibody levels were 67,224+/- 101,251 in the seroconverted MS group compared to 145,510+/- 99,669 in controls (n=489). When patient sera were assessed for binding to Clade A Spike, and VoC Delta and Omicron BA1 Spikes, most sera were able to bind the three different Spike antigens (n=61). However, Spike antibody immunoreactivity was decreased by 70% against Delta Spike and 90% for Omicron BA1 Spike compared to the original clade A Spike.As observed for Clade A Spike antibody, DMTs, such as ocrelizumab, fingolimod, and ofatumumab, decreased the antibody binding to Delta and Omicron Spike. Still, the pattern of antibody recognition was similar between the three Spikes and all DMTs analysed, i.e. alemtuzumab, natalizumab, teriflunomide, and interferons. Our data suggest that, irrespectively of DMTs, antibodies generated after vaccination did not bind Spike from recent VoCs to the same extent as the original Spike used in COVID-19 vaccines. Conclusion(s): Some DMTs reduce Spike antibody titres or prevent seroconversion. The sequence of Spike used in the first generation of vaccines may need to be updated for emerging VoC.
ABSTRACT
Introduction: Siponimod is approved in Australia for adults with secondary progressive multiple sclerosis (SPMS). Prescreen requirements for siponimod include a CYP2C9 genotype test to determine maintenance dosing. An integrated digital platform, 'MSGo', was developed by Novartis and RxMx to support Healthcare Professionals and their multiple sclerosis patients. Objective(s): Data derived exclusively from MSGo was utilised to explore the onboarding experience of siponimod patients in Australia. Aim(s): To provide real world evidence on siponimod for SPMS patients in Australia. Method(s): The study enrolled >350 adults with SPMS registered in MSGo for siponimod in Australia. Primary endpoint is the average time for onboarding with key secondary endpoints addressing adherence and variables that influence onboarding and adherence. Result(s): Final data extraction on April 20th, 2022 included 368 patients (median age of 59y).CYP2C9 genotype testing took a median of 19 days (95%CI 17-21) from registration and maintenance doses of 2mg (n=166) or 1mg (n=27) were initiated as per label recommendations;1mg was initiated for two rare allele genotypes (*1*5 and*1*11) in the absence of label recommendations. Mixture-cure modelling estimated that 58% of patients will ever initiate siponimod, with a median time to initiation of 56d (95%CI 47-59) from registration. Among those who initiated siponimod the most common reported reason for delayed initiation was 'waiting for vaccination'. Self-reporting of daily treatment, captured under the treatment reminder function in MSGo, had a drop-off of ~25% after the first week of initiation;a continued decline in reporting over time limited assessment of adherence. Continued self-reporting of daily dosing trended lower with older patients with only 28% of those >70y continuing to self-report at day 90 compared to 47-69% with the younger age groups. The study uncovered the important role of care partners, with Cox regression analyses demonstrating that SPMS patients who nominated a care partner were more likely to initiate (HR:2.1, 95%CI 1.5-3.0) and to continue self-reporting their daily medication (HR:2.2, 95%CI 1.3-3.7). A total of 90 patients discontinued the study;48 prior to and 42 after siponimod exposure. Conclusion(s): This study provides insights into siponimod onboarding for adults living with SPMS in Australia and demonstrates the impact of MSGo and care partner support during a period challenged by the COVID-19 pandemic.
ABSTRACT
Introduction: Siponimod is approved in Australia for adults with secondary progressive multiple sclerosis (SPMS). Initiating siponimod involves prescreening tests, including a CYP2C9 genotype test to determine siponimod maintenance dosing. Furthermore, patients undergo a 6-day titration prior to the maintenance phase. To support onboarding, an integrated digital platform, 'MSGo', has been developed by Novartis and RxMx® for Healthcare Professionals and their multiple sclerosis patients. Objective: Data derived exclusively from MSGo will be utilised to characterise the onboarding experience of siponimod patients in Australia. Aims: To provide real world evidence on siponimod for SPMS patients in Australia. Methods: The study will enrol 500 adults with SPMS registered in MSGo for siponimod treatment in Australia. The primary endpoint is the average time for onboarding with key secondary endpoints addressing adherence and the variables that influence onboarding and adherence. Results: As of April 19th, 2021, 211 patients have enrolled in the RWE study, with baseline patient characteristics revealing more females than males (70% vs 30%) and a median age range of 51-60 years. A total of 88 patients proceeded to at least the first titration dose;75 with at least one day of maintenance. Mixturecure modelling estimated a median time to initiation of 53 days in the predicted population of patients who will ever initiate on siponimod. Univariate Cox regression analyses demonstrated that patients who nominated a care partner at registration (n=27, 13%) appeared more likely to initiate siponimod earlier (p=0.017). A total of 163 CYP2C9 genotype assessments were performed through MSGo and the median time to receiving results from registration was 21 days (95% CI: 18 to 28 days). Of these, 87 patients had their maintenance dose selected in MSGo, with all but one patient having the recommended maintenance dose selected: 2 mg for CYP2C9∗1∗1 (n=58), ∗1∗2 (n=13), ∗2∗2 (n=1) and 1 mg for ∗1∗3 (n=10) and ∗2∗3 (n=4). 1 mg maintenance was selected for a patient with a rare ∗1∗5 genotype which currently has no dose recommendation. A total of 7 patients unenrolled from MSGo prior to siponimod initiation whilst 10 patients ceased after siponimod initiation. Conclusions: These interim results provide early insights into the siponimod onboarding experience for SPMS patients in Australia and demonstrate the utility of MSGo during a period challenged by the COVID-19 pandemic.