ABSTRACT
The PANORAMA survey aimed to assess current treatment practice for individuals with new diagnoses of relapsing-remitting multiple sclerosis (RRMS) in the United Kingdom and to explore variations in treatment approaches with an emphasis on escalation vs early high-efficacy treatment (HET) and treatment goals.
Health care professionals (HCPs) from the UK treating patients with RRMS took part in interviews facilitated by a structured questionnaire. Data were analyzed descriptively using quantitative or qualitative methods, as appropriate.
Thirty-eight HCPs from 38 UK centers took part in the survey, including 20 MS consultants and 13 MS specialist nurses. Seventy-four percent (n = 28 of 38) of HCPs strongly agreed and 24% (9 of 38) agreed that early treatment is essential for better outcomes. HCPs reported that they currently treat a mean (SD) of 58.3% (20.8%) and 42.1% (21.8%) of patients with new diagnoses of RRMS with early HET or escalation approaches, respectively. Thirty-four percent (13 of 38) of HCPs reported a discrepancy between current treatment approach and the approach they would like to take, which would be 66.2% favoring early HET and 33.8% favoring escalation approaches. The factors influencing the choice of treatment approach were overall patient health profile (45%, 17 of 38) and patient choice (39%, 15 of 38). The most important treatment goals were to reduce relapses (63%, 24 of 38), delay disability progression (58%, 22 of 38), and maintain quality of life (50%, 19 of 38).
The survey highlights variation among HCPs in the UK in current vs ideal use of escalation or early HET approaches and factors influencing choice of treatment approach.
Relapsing-remitting multiple sclerosis (RRMS) is the most common form of MS and is characterized by recurrent episodes of neurological impairment interspersed with periods of remission. In addition to patient preference, many factors impact the choice of the first disease-modifying therapy (DMT) for individuals with RRMS ranging from those related to the patient (clinical, social, and psychological), treating clinician (role, ability to prescribe DMTs, education, and attitude about risk) and health care setting (drug licenses, reimbursement, guidelines, and infrastructure).1
Early initiation of MS treatment is recommended by the European Committee for Treatment and Research in Multiple Sclerosis and the European Academy of Neurology2 and is widely accepted within the MS community. However, given the limited evidence from randomized trials, debate remains as to whether taking an escalation approach or early high-efficacy treatment (HET) will achieve the best outcomes for patients with RRMS.3 The escalation approach encourages the use of moderate efficacy first-line DMT (usually with acceptable safety profiles), with escalation to a high-efficacy DMT only after the occurrence of breakthrough disease activity (eg, relapse). Due to starting with lower-efficacy DMTs, there is a risk of undertreatment associated with this approach.3 In contrast, the early HET approach advocates the use of high efficacy first-line DMTs with the greater potential for safety risk. Given that use of increasingly efficacious medications must be balanced against their respective safety profiles and that multiple classes of DMTs are available for treatment in RRMS (varying in mechanism, efficacy, safety, and mode of administration), treatment decisions for clinicians and patients with RRMS have become complex.2
The National Institute of Health and Care Excellence developed guidelines for the use of licensed DMTs in MS for England, Wales, and Northern Ireland.4 The guidelines for the National Health Service (NHS) Scotland were developed by the Scottish Medicines Consortium.5 NHS prescribing centers are expected to take guideline recommendations into account. Additionally, there are reimbursement criteria in place across NHS England that may impact DMT access.
A recent qualitative study in the UK investigated how people with RRMS weigh the pros and cons of DMT choice, focusing on perceptions of effectiveness and risks when new treatments are considered.6 It is also important to understand the current practice on clinical treatment decision-making and the factors that health care professionals (HCPs) consider when making these decisions. To address this question, we conducted the PANORAMA survey asking UK HCPs about RRMS treatment approaches. The main objective was to assess current treatment practice for patients with a new diagnosis of RRMS in the UK and to explore variations in treatment approaches with an emphasis on escalation vs early HET and treatment goals.
METHODS
Study Design, Setting, and Participants
Novartis medical science liaisons (MSLs) approached 154 HCPs involved in treating patients with RRMS between March 2021 and August 2021 to take part in a survey via email. To minimize participant selection bias, these 154 participants were chosen using a random sampling approach of all UK HCPs involved in MS DMT management (BOX S1). All participants who expressed an interest in taking part within the time frame allowed for responses were included. The aim was to gather opinions from all MS treatment centers across the UK. This survey was exempt from NHS Research Ethics Committee review according to section 2.3.14 of the Governance Arrangements for Research Ethics Committees (REC), which states that REC approval in the UK is not required for research involving NHS staff recruited by virtue of their professional role.7
The Survey
HCPs were interviewed by MSLs from Novartis with interviews carried out predominantly by video call, whereas the rest were conducted via telephone call. The survey interview was carried out in conversation with the HCPs, with the interviewer completing the structured questionnaire based on the answers received. The questionnaire was designed collaboratively with 2 consultant neurologists and an MS specialist nurse to ensure that clinically valuable data were collected. It consisted of a mixture of fixed-choice and open-ended (free response) questions.
Statistical Methods
Responses were analyzed descriptively by the OPEN Health company on a question-by-question basis, using quantitative or qualitative methods, as appropriate. Descriptive statistics of distribution and dispersion were reported for quantitative variables and measures of frequency were described for categorical variables. In cases where free responses fell into categories that had been prespecified, the response was included as part of the relevant category only when it was not a duplication. All other free responses were reviewed and organized into thematic categories. Respondents were not required to answer all questions; therefore, the calculated percentages were based on the total number of responses received for each question (with the number of responses/denominator specified alongside each result). Data were analyzed by respondent role and length of time worked in current role, where appropriate.
RESULTS
Respondent Characteristics
A total of 38 HCPs (n = 38 of 154, 25% response rate) from 38 centers spread geographically across the UK (England [82%, n = 31 of 38], Scotland [11%, n = 4 of 38], Wales [5%, n = 2 of 38], Northern Ireland [3%, n = 1 of 38]) took part in the survey. Of these, 20 (53%) identified as MS consultants, 13 (34%) as MS specialist nurses, 4 (11%) as neurologists with an interest in MS, and 1 (3%) as an MS specialist practitioner. Of the MS specialist nurses, 6 (46%) reported the ability to prescribe DMT and 7 (54%) could not. Of the 38 HCPs, 34% (n = 13 of 38) had been in their current role for less than 6 years, 29% (n = 11 of 38) for 6 to 10 years, 13% (n = 5 of 38) for 11 to 15 years and 24% (n = 9 of 38) for more than 15 years. The estimated median (IQR) number of patients with MS currently being treated per respondent's center was 1150 (795-1850 [n = 36 of 38]) patients.
Treatment Approach
The majority of HCPs either strongly agreed (74%; n = 28 of 38) or agreed (24%; n = 9 of 38) that early treatment is essential for better outcomes for most patients; 3% (n = 1 of 38) of HCPs disagreed. The mean (SD) percentage of patients with new diagnoses of RRMS estimated by HCPs (n = 37) to be treated with early HET or escalation approaches at their center was 58.3% (20.8%) and 42.1% (21.8%), respectively (FIGURE 1).
Estimated Percentage of Patients With Relapsing-Remitting Multiple Sclerosis by Treatment Approach
Estimated Percentage of Patients With Relapsing-Remitting Multiple Sclerosis by Treatment Approach
Most respondents (66%, n = 25 of 38) reported that the estimated proportion of patients currently treated with early HET vs escalation approaches at their center is reflective of the proportion of patients they would ideally like to treat using each approach. In contrast, 34% (n = 13 of 38) of HCPs reported a discrepancy between the treatment approach currently taken and the approach they would like to take; these 13 HCPs reported that they would ideally like to treat (mean [SD]) 66.2% (18.0%) of patients with early HET approaches and 33.8% (18.0%) with escalation approaches, citing reimbursement (58%, n = 7 of 12), guidelines (33%, n = 4 of 12), and other reasons (33%, n = 4 of 12; ie, family planning, patient concerns over risk, cost, and no reason specified) as the most common reasons for difference. Overall, HCPs reported that the factors most likely to influence their choice of treatment approach for patients with new diagnoses of RRMS were the overall patient health profile (45%; n = 17 of 38), patient choice (39%; n = 15 of 38), and disease severity (37%; n = 14 of 38; FIGURE 2).
Treatment Goals
When asked to select the 3 most important treatment goals for patients with new diagnoses of RRMS, HCPs reported reducing relapses (63%; n = 24 of 38), delaying progression to disability (58%; n = 22 of 38), and maintaining quality of life (QOL; 50%; n = 19 of 38; FIGURE S1).
When grouped by job role, 64% (n = 9 of 14) of nurses reported maintaining QOL to be among their top 3 treatment goals compared with 42% (n = 10 of 24) of MS specialists and general neurologists (for full results see TABLE S1). HCPs who had been in their current role less than 6 years and those who had been in their role for 6 to 10 years chose the same top 4 treatment goals (modifying or reducing relapses, delaying progression to disability, maintaining an acceptable quality of life and no evidence of disease activity [NEDA]), albeit in a slightly different order. HCPs who had been in their role for more than 10 years also placed relapse reduction and maintaining an acceptable QOL in their top 4 but not delaying progression to disability or NEDA, which were chosen by only 7% and 14% of HCPs in this group, respectively. Instead, finding an approach that fits the patient's lifestyle and educating the patient were among the top 4 responses for these HCPs. For full results, see TABLE S2.
Treatment Setting
The majority of HCPs stated that the primary treatment center where they managed the majority of their patients with MS were either tertiary hospitals (39%; n = 15 of 38) or district hospitals (32%; n = 12 of 38). This was followed by 37% (n =14 of 38) of HCPs who considered their primary treatment center to be a hub (centers with a full array of services available), 16% (n = 6 of 38) of HCPs who considered themselves to be from spoke treatment centers (centers in which limited services are available and patients are routed to a relevant center for more specialized services and treatments), and 11% (n = 4 of 38) from centers that are not considered a spoke but refer patients to other hospitals for certain DMTs (hereafter, all nonhub centers are referred to as referring centers [n = 10]). Respondents were asked to choose all applicable descriptors of their treatment center and, thus, results are not mutually exclusive (sum up to > 100%).
HCPs from referring centers reported that a neurologist (70%, n = 7 of 10), MS specialist nurse (60%, n = 6 of 10), or no one (30%, n = 3 of 10) attended hub multidisciplinary meetings to discuss patients with RRMS. The most common reason to refer patients to a hub was when DMT could not be prescribed at the referring center (90%, n = 9 of 10) and the mean (SD) estimated wait time for patients to be seen at the hub following referral was 67.9 (66.5) days (n = 8). See TABLES S3 and S4 for further details. Eighty percent (n = 8 of 10) of HCPs from referring centers reported that the distance between the hub and spoke center influences treatment choice; reasons given for this included patient preference for treatments that do not require traveling or missing work (100%; n = 6 of 6) and for treatments that can be given by their local health care team (17%; n = 1 of 6). Two of 8 HCPs did not provide a reason.
Patient Education and Discussion
Of 38 HCPs, 82% (n = 31 of 38) reported that they always discuss different treatment approaches with patients with new diagnoses of RRMS and 18% (n = 7 of 38) sometimes discuss different treatment approaches. The HCPs perceived that an estimated (mean [SD]) 45.9% (27.9%) of patients with new RRMS diagnoses would prefer to initiate a high-efficacy DMT. HCPs (n = 38) reported that when deciding on a treatment approach, patients considered convenience of treatment (76%; n = 29 of 38) and adverse effect profile (68%; n = 26 of 38) the most and travel plans/lifestyle and well-established programs/known DMTs (both 11% [n = 4 of 38]) the least. Thirty-seven percent of HCPs (n = 14 of 38) believed that patients would consider clinical efficacy data when deciding on a treatment approach. See TABLE S5 for more details.
DISCUSSION
This survey of UK HCPs aimed to provide an understanding of clinical treatment decision-making and the factors underlying these decisions and to describe the treatment of patients with new diagnoses of RRMS. The results show that there is variation in HCPs’ treatment goal priorities and that the majority of HCPs agree that early treatment of RRMS is essential. Results also indicate that although escalation and early HET treatment approaches are estimated to be used in similar proportions of patients overall, a wide variability remains. In addition, a third of HCPs do not prescribe DMT in their ideal way and more would prefer to treat a higher proportion of patients with the early HET approach. Also, the physical distance between a referring center and an MS treatment hub is an influencing factor in treatment choice.
That most HCPs surveyed indicated early treatment of RRMS is essential is in line with the 2015 guidelines from the Association of British Neurologists (ABN).8 This is also in line with the published findings of studies, such as those by Lefort et al, who retrospectively assessed the impact of early treatment (defined as initiation within the first 12 months from MS clinical onset) vs later treatment (defined as initiation after 12 months) across treatment centers in France between 1996 and 2012.9 The study observed that in a cohort of 5279 patients with RRMS, 1882 (36%) could be defined as having received early treatment and that, whether matched for age or stratified by age, early treatment led to significant delays in the length of time it took for patients to progress to a sustained Expanded Disability Status Scale (EDSS) score of 3.0.9 Several studies support the theory of a therapeutic window in the early stages of MS, with early DMT initiation being observed to improve both clinical and patient-centered outcomes in the short and long term.10-14
In line with the review by Ontaneda et al, HCPs in this survey reported that the escalation treatment approach was used slightly more frequently than the early HET approach in the UK.3 However, approximately 33% of HCPs subsequently reported that, ideally, they would treat two-thirds of patients with RRMS with early HET. As yet, there is no evidence from randomized trials to support a first-line treatment approach. However, data from an international secondary-data study (using data from national MS registries) that compared the treatment approaches of Sweden (n=2700) and Denmark (n = 2161) between 2013 and 2016 observed that using a more efficacious DMT as initial treatment was superior to treatment escalation in patients with RRMS.15 Another real-world study investigating outcomes in patients with MS in Wales observed that 5-year outcomes as measured by EDSS were significantly more favorable in patients on early HET compared with those on a first-line escalation approach.16 Thus, ongoing clinical trials, including TREAT-MS (NCT03500328) and DELIVER-MS (NCT03535298), will provide important information on this moving forward.17
When asked their top 3 goals when treating patients with new diagnoses of RRMS, in addition to the clinical factors of modifying/reducing relapse and delaying progression to disability, maintaining QOL was cited by 64% of nurses and 42% of MS specialists/general neurologists. In an online cross-sectional survey, neurologists (n = 101) reported slowing the rate of brain volume loss, reducing 2-year disability progression, risk of infection, and 1-year relapse rate as treatment goals for patients without highly active disease. Lowering the 1-year relapse rate and slowing the rates of brain volume loss and 2-year disability progression were rated as treatment goals for patients with highly active disease.18 It is interesting to note that HCPs who had been in their role for more than 10 years included factors such as patient partnership, educating the patient, and finding an approach that fits the patient's lifestyle (albeit, not in the top 3). Maintaining QOL is not a clear clinical outcome outlined in the 2015 ABN guidelines and, as a whole, these results suggest that HCPs consider these wider factors alongside traditional clinical efficacy parameters when making treatment decisions.8 QOL can be affected by multiple factors including those that are mental, physical, and psychosocial. Mental health has been found to affect QOL more than physical health in the early years of RRMS, suggesting that this domain could be targeted to improve QOL for patients with RRMS.19 Anxiety about and fear of relapse, in particular, appears to be an important factor to be addressed in order to improve QOL.20,21
The NHS hub and spoke arrangement is a working organizational model in which services are arranged across a wider network of service delivery centers.22 Anchor service delivery centers (hubs) offering a full range of services are supplemented by secondary service centers (spokes) that offer a smaller array of services and refer patients to the hub center for treatments that are not or cannot be delivered locally. In this survey, HCPs from referring centers report that the most common reason to refer patients to hub centers was prescription of DMTs. HCPs reported that the distance between the hub and spoke centers influenced treatment choices, as patients avoided the need to travel or take time off from work. These results reinforce findings from a systematic review concluding that a distance decay effect (whereby patients living farther away from health care centers experience worse health outcomes) cannot be ruled out due to the potential for delayed medical care and the patient not receiving the most efficacious treatment.23 Consequently, our results support the likely need to invest resources into bringing care and access to all treatments closer to the patient's home.
Due to the inherent design of this survey, there are some important limitations. HCPs’ answers may be subject to recall bias, as they were subjective and based upon recollection. Survey responses could also have been affected by nonresponse bias with those who chose to take part potentially having different views, experiences, and approaches than those who did not take part. However, the survey did include a range of specialist HCPs from across the UK. Although the survey may have been affected by the COVID-19 pandemic and its aftermath, the observed 25% response rate is broadly consistent with other neurology clinical practice surveys.24 In addition, responses were reported by HCPs and not observed. As each center was represented by 1 HCP for best national representation, this survey was unable to observe any possible within-center variation in clinician practice. This survey included a small number of HCPs who represented a small number of health care centers across the UK. Thus, it may not represent the entire HCP community and health care centers of the UK. However, a random sampling approach was used to minimize any bias in sampling. Multiple interviewers were involved in carrying out the survey and, subsequently, there could have been variation in the way that some questions were conveyed and interpreted. The impact of this was minimized by the semistructured form of the questionnaire.
The authors, with both medical and nursing expertise, planned comprehensively and collected data from a wide range of MS centers in the UK. We used an industry partner to collect nonpatient direct data from many centers, which is a strength of this manuscript. Novartis has medications that fall under both treatment approaches. We don't believe the results to have been influenced by this choice, but we acknowledge the potential of reporting bias due to the involvement of Novartis MSLs in arranging and conducting the survey interviews.
While these limitations are inherent to the study design, the randomized invitation to MS clinicians included geographically dispersed centers across the UK and multiple center types and HCP roles, lending strength and breadth to the survey in informing on the self-reported current practice of HCPs treating patients with RRMS. At the time of writing, several new DMT options have been licensed and are available for patients being treated in the NHS. Each of these new DMT options has their own considerations and, thus, future research might explore how the introduction of these DMTs has changed practices and beliefs around treatment approaches since the original survey.
CONCLUSIONS
The survey highlighted significant variation among HCPs in reported use of early HET or escalation treatment approaches and factors reported to influence the choice of treatment. However, the majority of HCPs agreed that early treatment of RRMS is essential. Moving forward, we hope that the results we have presented stimulate discussion around the standardization of treatment approaches and goals for patients with RRMS to provide optimal care irrespective of treatment setting.
Most health care professionals (HCPs) agreed that early treatment of relapsing-remitting multiple sclerosis (RRMS) is essential.
Use of escalation or early high-efficacy treatment varied significantly, and respondents reported a discrepancy in ideal vs actual treatment approaches.
Treatment goals for RRMS varied for HCPs according to job role and time worked in that role.
Distance to a referral center influenced treatment received.
ACKNOWLEDGMENTS:
The authors thank the health care professionals who participated in the survey and the Novartis UK Medical Team who contributed to the collection of the data. OPEN Health (Marlow, UK) supported the authors in conducting the survey, analyzing the results, and medical writing (especially Will Cottam, PhD). This survey was funded by Novartis Pharmaceuticals UK Ltd. The authors also thank Shashank Jain (Novartis Healthcare Pvt Ltd, India) for his medical writing assistance.
REFERENCES
FUNDING: Financial support for medical writing assistance was provided by Novartis Pharmaceuticals UK Ltd. Authors had full control of the content and made the final decisions on all aspects of this article. Novartis Pharmaceuticals UK organized the PANORAMA survey in collaboration with the steering committee and provided the financial support for this work.
CONFLICTS OF INTEREST: Nikos Evangelou, DPhil, has received research funding from the Patient-Centered Outcomes Research Institute and Roche and personal compensation for speaking, advisory board work, and travel from Biogen, Merck, and Novartis. Miriam Mattoscio, MD, PhD, has served as Scientific Committee Member of the Italian Multiple Sclerosis Foundation (FISM) and received compensation for participating in scientific committee meetings, advisory boards, travel support, and speaker honoraria from FISM, Merck Serono, MS Academy, Novartis, and Roche. Mhairi Coutts, RGN, has received honorarium and speaker fees from Bristol Myers Squibb and Novartis, and has participated in an advisory board for Coloplast. Manoharan Andiappan, PhD, was an employee of OPEN Health when the work was undertaken. Teresa Sawtell, MRes, was an employee of Novartis Pharmaceuticals UK Ltd while the work was undertaken and holds Novartis stock or stock options. Katherine Rhys, BS, is an employee of Novartis Pharmaceuticals UK Ltd.
PRIOR PRESENTATION: This work was presented in poster form at the MS Trust Annual Conference; March 27-29, 2022; Hinckley, United Kingdom; and at the Association of British Neurologists Annual Meeting; May 18-20, 2022; Harrogate, United Kingdom.
Author notes
At the time of the study