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Relapse prevalence, symptoms, and health care engagement: patient insights from the Multiple Sclerosis in America 2017 survey

Open AccessPublished:September 06, 2018DOI:https://doi.org/10.1016/j.msard.2018.09.002

      Highlights

      • Online survey of 5,300 MS patients, 50% moderately and 14% severely disabled.
      • 1 in 5 reported > 2 relapses a year and 2/3 with serious relapse symptoms.
      • Those relapsing most often were least apt to contact their HCP.
      • Barriers to contact include lack of HCP helpfulness and medication effectiveness.
      • HCP follow-up was variable, yet significantly linked to patient satisfaction.

      Abstract

      Background

      Underestimation of relapse in multiple sclerosis (MS) is detrimental to the patient as well as to their relationship with their MS healthcare professional (HCP).

      Objective

      To obtain direct insight into relapse prevalence, symptoms, and HCP engagement from patients with MS who responded to the Multiple Sclerosis in America (MSIA) 2017 survey.

      Methods

      Information on patient demographics, health insurance coverage, symptoms, disability, relapses, and related HCP interactions were captured. Descriptive analyses were conducted and relapses were annualized. Chi-square tests were used to evaluate frequency of patient engagement, i.e. speaking with or seeing their HCP during relapse with annualized relapse frequency and topics discussed.

      Results

      Of the 5,311 patient-respondents, the mean age was 51.2 years (84.3% female, 89.3% Caucasian); 40.1% were on disability, and 96.8% had health insurance coverage. A total of 72.2% of patients were diagnosed with relapsing-remitting MS (RRMS); 74.8% of patients not reporting a diagnosis of primary progressive MS (PPMS) (n = 4819) were using disease-modifying therapy. In the 2 years preceding the survey, 73.1% experienced a relapse for a median number of 2 relapses; this corresponded to an annualized relapse distribution among all patients of 44.1% with < 1 relapse, 35.5% with 1–2 relapses, and 20.2% with > 2 relapses. In patients reporting relapses, 62.5% cited an average relapse duration of < 1 month, 10.9% cited 1–2 months, and 13.6% cited > 2 months (12.9% were unsure/didn't recall). Leading symptoms experienced with MS relapse were fatigue (77.4%), numbness/tingling (70.0%), and walking or balance issues (68.8%). With respect to HCP engagement during relapse, 46.9% of patients reported doing so always/often, vs. sometimes (27.3%), rarely (18.5%), and never (7.3%). The most common reasons cited for not engaging an HCP were that the relapse was not severe enough (57.9%), the HCP was unhelpful or didn't specifically tell the patient to contact them (30.9%), the treatment didn't work well or wasn't tolerated (25.6%), or the preference to manage alone (24.4%). A higher percentage of patients with 1 relapse coincided with the highest frequency of HCP engagement during relapse, and the highest percentage of patients with ≥ 5 relapses coincided with the lowest frequency of HCP engagement during relapse. Key relapse-related and MS-related topics were discussed more by patients who always/often engage their HCP during relapse. HCP follow-up after relapse was variable, with 35.0% of patients reporting follow-up within 1 month of first contact, 50.3% reporting follow-up at the next office visit, and 14.7% reporting no follow-up.

      Conclusion

      MS relapse remains particularly challenging for certain patients; some experience > 2 relapses in 1 year, relapse durations > 1 month, and relapse symptoms that interfere with daily functioning (e.g. walking/balance by 68.8%). Approximately 25% of patients reported rarely or never engaging their HCP during relapse. Common reasons for not engaging, like HCP helpfulness and treatment effectiveness/tolerance, warrant further exploration. Results indicating the benefits of timely touchpoints on both the part of the patient and HCP during relapse include the relationship between higher frequency of engagement with lower relapse frequency and more discussion of both relapse-related and MS-related discussion topics. Survey limitations apply.

      Keywords

      1. Introduction

      Relapses are a hallmark of multiple sclerosis (MS); the relapsing-remitting form, RRMS, affects approximately 85% of the MS population [
      • Berkovich R.R.
      Acute multiple sclerosis relapse.
      ,
      • Goodin D.S.
      • Frohman E.M.
      • Garmany G.P.
      • et al.
      Therapeutics and technology assessment subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines.
      ,
      National Multiple Sclerosis Society
      What is MS?: Relapsing Remitting MS.
      ]. While relapses are more common in patients with RRMS, all types of MS patients are subject to relapse, including those with primary or secondary progressive MS [
      • Goodin D.S.
      • Frohman E.M.
      • Garmany G.P.
      • et al.
      Therapeutics and technology assessment subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines.
      ,
      • Sellebjerg F.
      • Barnes D.
      • Filippini G.
      • et al.
      EFNS guideline on treatment of multiple sclerosis relapses: report of an EFNS task force on treatment of multiple sclerosis relapses.
      ]. A relapse or exacerbation is a worsening of symptoms or the appearance of new neurologic symptoms during an episode of acute disease activity in the absence of fever or infection, followed by a period of partial or complete recovery separated by at least 30 days from the onset of the last relapse, which lasts for more than 24 hours [
      • Berkovich R.R.
      Acute multiple sclerosis relapse.
      ; NMSS;
      • Sellebjerg F.
      • Barnes D.
      • Filippini G.
      • et al.
      EFNS guideline on treatment of multiple sclerosis relapses: report of an EFNS task force on treatment of multiple sclerosis relapses.
      ;
      National Multiple Sclerosis Society
      Managing Relapses.
      ;
      • Lublin F.D.
      • Reingold S.C.
      • Cohen J.A.
      • et al.
      Defining the clinical course of multiple sclerosis.
      ,
      • McDonald W.I.
      • Compston A.
      • Edan G.
      • et al.
      Recommended diagnostic criteria for multiple sclerosis: guidelines from the international panel on the diagnosis of multiple sclerosis.
      ]. Pathophysiologically, a relapse is caused by inflammatory and demyelinating lesions in any part of the central nervous system [
      • Goodin D.S.
      • Frohman E.M.
      • Garmany G.P.
      • et al.
      Therapeutics and technology assessment subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines.
      ,
      • Sellebjerg F.
      • Barnes D.
      • Filippini G.
      • et al.
      EFNS guideline on treatment of multiple sclerosis relapses: report of an EFNS task force on treatment of multiple sclerosis relapses.
      ,
      • Lublin F.D.
      • Reingold S.C.
      • Cohen J.A.
      • et al.
      Defining the clinical course of multiple sclerosis.
      ,
      • Repovic P
      • Lublin F.D.
      Treatment of multiple sclerosis exacerbations.
      ].
      Understanding the true frequency of MS relapse has been challenging. Specific patient types are included in clinical studies and are typically not observed for sufficiently long periods [
      • Kalincik T.
      Multiple sclerosis relapses: epidemiology, outcomes and management: a systematic review.
      ,
      • Ollendorf D.A.
      • Jilinskaia E.
      • Oleen-Burkey M.
      Clinical and economic impact of glatiramer acetate versus beta interferon therapy among patients with multiple sclerosis in a managed care population.
      ]. Recent clinical trials for disease-modifying treatments (DMTs) have reported variable annualized relapse rates of 0.46–1.8 before the trial (mean of 1.5 relapses) and 0.18–0.49 after the trial [Cohen et al., 2012;
      • Derfuss T.
      • Ontandeda D.
      • Nicholas J.
      • Meng X.
      • Hawker K.
      Relapse rates in patients with multiple sclerosis treated with fingolimod: subgroup analyses of pooled data from three phase 3 trials.
      ]. Studies based on administrative health insurance claims data quantify MS relapse based on patients’ healthcare-seeking behavior and reflect mostly commercially insured patient populations which may be healthier or of higher socioeconomic status [
      • Ollendorf D.A.
      • Jilinskaia E.
      • Oleen-Burkey M.
      Clinical and economic impact of glatiramer acetate versus beta interferon therapy among patients with multiple sclerosis in a managed care population.
      ]. This has likely led to an underestimation of relapse frequency, and possibly relapse duration as well. Obtaining an estimate of the prevalence of MS relapse from patients may provide a different and much-needed perspective by reflecting a broader cross-section of patients at various places in the MS disease spectrum. This range of results from various type of studies is central to developing a comprehensive and well-informed understanding of MS relapse and its distribution among the patient population, which can be married with other estimates.
      Although DMTs aim to reduce the frequency of relapses, they do not help in the targeted management of relapses. While treatment of MS relapse enhances the rate of recovery from short-term functional disability related to a period of relapse [
      • Goodin D.S.
      • Frohman E.M.
      • Garmany G.P.
      • et al.
      Therapeutics and technology assessment subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines.
      ,
      • Sellebjerg F.
      • Barnes D.
      • Filippini G.
      • et al.
      EFNS guideline on treatment of multiple sclerosis relapses: report of an EFNS task force on treatment of multiple sclerosis relapses.
      ], residual deficits stemming from incomplete recovery can result in accrued impairment, which may impact longer-term disease prognosis [
      • Goodin D.S.
      • Reder A.T.
      • Bermel R.A.
      • et al.
      Relapses in multiple sclerosis: Relationship to disability.
      ,
      • Repovic P
      • Lublin F.D.
      Treatment of multiple sclerosis exacerbations.
      ,
      • Lublin F.D.
      The incomplete nature of multiple sclerosis relapse resolution.
      ,
      • Lublin F.D.
      • Baier M.
      • Cutter G.
      Effect of relapses on development of residual deficit in multiple sclerosis.
      ,
      • Stoppe M.
      • Busch M.
      • Krizek L.
      • Bergh F.T.
      Outcome of MS relapses in the era of disease-modifying therapy.
      ]. Thus, timely detection, evaluation, and treatment of relapse to resolution are critical priorities [
      • Berkovich R.R.
      Acute multiple sclerosis relapse.
      ,
      National Multiple Sclerosis Society
      Recommendations regarding corticosteroids in the management of multiple sclerosis.
      ,
      • Stoppe M.
      • Busch M.
      • Krizek L.
      • Bergh F.T.
      Outcome of MS relapses in the era of disease-modifying therapy.
      ]. MS care providers, as well, play an integral role. Relapses are powerful reminders to patients of the unpredictability of MS and remain one of patients’ biggest concerns about the disease [
      • Berkovich R.R.
      Acute multiple sclerosis relapse.
      ; Repovic and Lubin, 2011]. Consequently, successful relapse management allows patients a sense of control over their disease [
      • Berkovich R.R.
      Acute multiple sclerosis relapse.
      ; Repovic and Lubin, 2011]. This, in turn, may engender patients’ belief in treatment and trust in their healthcare team.
      In addition to shaping meaningful care, the foundational relationship between the patient with MS and their MS healthcare provider (MS-HCP, hereafter referred to as HCP) influences treatment decisions and patient self-management that affect health outcomes. In a recent study that surveyed patients with MS and their HCPs (primarily neurologists), Tintoré et al. found that the openness of patient-physician dialogue affected patient satisfaction with their overall MS treatment (with DMTs) and outcomes, although the study did not evaluate the occurrence of relapses nor the effect on relapses [
      • Tintoré M.
      • Alexander M.
      • Costello K.
      • et al.
      The state of multiple sclerosis: current insight into the patient/health care provider relationship, treatment challenges, and satisfaction.
      ].
      Similarly, the present study also uses a survey of MS patients as the source of information about the relationship with their HCP. The aim of this study was to obtain direct insight into the patients’ experiences with MS relapse, their associated healthcare seeking behavior, and their perceptions regarding MS care, captured in the Multiple Sclerosis in America (MSIA) 2017 survey [

      Data on file. Health Union, LLC. 2017.

      ].

      2. Materials and methods

      The MSIA 2017 survey and recruitment assets were submitted to Pearl Institutional Review Board and received an exemption determination. The survey was subsequently fielded by Health Union during the first quarter of 2017 to MS patients via multiple online sources, including MultipleSclerosis.net and the site's corresponding Facebook page. No honorarium was offered and standard data privacy and confidentiality procedures were followed.
      The survey contained 124 questions directed to MS patients. All patients attested to being at least 18 years of age, diagnosed with MS by an HCP, and living in the U.S. Eighteen questions were used in the present study and are shown in the Appendix; these focus on patient demographics, health insurance coverage, employment, disability (using the Patient-Determined Disease Steps [PDDS], a self-assessment scale of MS disease status), MS diagnosis and symptoms, relapse history and experience, and patient-HCP engagement [
      • Hohol M.J.
      • Orav E.J.
      • Weiner H.L.
      Disease Steps in multiple sclerosis: A simple approach to evaluate disease progression.
      ]. The PDDS, as developed by the North American Research Consortium on Multiple Sclerosis (NARCOMS), rates disability primarily based on the effect of MS on the patient's ability to walk, although it also takes MS symptoms and overall daily activities into consideration. Disability is considered mild (PDDS score 0–2) if symptoms are minor or walking is unaffected, moderate (PDDS score 3–5) if gait is affected or patient requires use of a cane, and severe (PDDS score 6–8) if the patient requires bilateral support, a wheelchair, or is bedridden [
      • Hohol M.J.
      • Orav E.J.
      • Weiner H.L.
      Disease Steps in multiple sclerosis: A simple approach to evaluate disease progression.
      ]. Certain questions were conditionally asked of survey participants based upon prior survey response (e.g., those related to relapse experience were posed only to those reporting relapse). The relevant survey question(s) from the Appendix and the associated sample size in each section of the tables and in each figure are noted. Unless otherwise specified, the population size for each question is the total sample of 5,311.

      3. Data analysis

      Patient demographics as well as MS-related and relapse-related characteristics were analyzed descriptively. The number of relapses over the 2-year period preceding the survey participation were annualized and stratified into three groups by relapse frequency: < 1, 1–2, and > 2. Patient-HCP engagement during relapse was defined as speaking with or seeing their HCP during relapse; responses were categorized into always/often, sometimes, and rarely/never.
      Relapse symptoms experienced over the 2-year period preceding the survey participation were categorized into 7 functional systems (Table 1). Each relapse symptom was categorized into 1 functional system. In a small number of patients, relapse symptoms could not be categorized into functional systems (e.g., “other symptom not listed”) and were therefore excluded from this part of the analysis [Multiple Sclerosis Trust, 2017;
      National Multiple Sclerosis Society
      Glossary.
      ;
      National Multiple Sclerosis Society
      Kurtzke Functional Systems Scores (FSS).
      ;
      National Multiple Sclerosis Society
      MS Symptoms.
      ; Health Union, 2015;
      Multiple Sclerosis.net Editorial Team
      Migraines and MS.
      ,
      • Hersh CM
      • Fox RJ
      Multiple Sclerosis.
      ]. Fatigue was categorized separately given its constitutional nature and its effect on many different functional systems. Frequencies were generated for the functional systems affected. Tetrachoric correlations (rtet) were calculated to determine interrelationships between the functional systems [
      • Ekstrom J
      The Phi-coefficient, the Tetrachoric Correlation Coefficient, and the Pearson-Yule Debate.
      ]. Moderate positive associations were defined as rtet = 0.5–0.7, while weak positive associations and no association were defined as rtet = 0.3–0.5 and rtet< 0.3, respectively [
      • Mukaka M.M
      A guide to appropriate use of correlation coefficient in medical research.
      ].
      Table 1Categorization of relapse symptoms into functional systems.
      Functional SystemPyramidalFatigue
      Constitutional symptom, therefore separated from functional systems. Note: (N = 3,857; Q10).
      CerebellarBrainstemSensoryBladder/BowelCerebralVisual
      Symptoms• Foot drop
      Multiple Sclerosis Trust
      A-Z of MS.


      • Muscle spasms/spasticity [
      National Multiple Sclerosis Society
      Glossary.
      ]

      • Muscle weakness [
      National Multiple Sclerosis Society
      Glossary.
      ]

      • Paralysis [NMSS Kurtzke FSS, 2018]
      • Fatigue [NMSS Kurtzke FSS, 2018]• Loss of coordination [
      National Multiple Sclerosis Society
      Glossary.
      ]

      • Walking/balance/

      coordination problems [
      National Multiple Sclerosis Society
      Glossary.
      ]

      • Tremors [NMSS Kurtzke FSS, 2018]
      • Speech difficulties [NMSS Kurtzke FSS, 2018]

      • Trouble swallowing [NMSS Kurtzke FSS, 2018]

      • Hearing issues/loss [
      National Multiple Sclerosis Society
      MS Symptoms.
      ]

      • Sensitivity to sound [
      National Multiple Sclerosis Society
      MS Symptoms.
      ]

      • Dizziness/vertigo/

      lightheadedness [
      Health Union LLC. MS Symptoms
      ]

      • Headaches/

      migraines [MS.net Migraines and MS, 2017]
      • Heat sensitivity/ intolerance [
      National Multiple Sclerosis Society
      Glossary.
      ]

      • Cold sensitivity/ intolerance [
      National Multiple Sclerosis Society
      Glossary.
      ]

      • Numbness, tingling, or other altered sensations (eg, “pins and needles”) [
      National Multiple Sclerosis Society
      Glossary.
      ]

      • Pain [NMSS Kurtzke FSS, 2018]

      • Sexual dysfunction
      Multiple Sclerosis Trust
      A-Z of MS.
      • Bladder problems [NMSS Kurtzke FSS, 2018]

      • Bowel problems [NMSS Kurtzke FSS, 2018]
      • Anxiety
      Multiple Sclerosis Trust
      A-Z of MS.


      • Cognitive dysfunction (memory loss, difficulty concentrating, brain fog) [
      National Multiple Sclerosis Society
      Glossary.
      ]

      • Depression or mood changes [NMSS Kurtzke FSS, 2018]
      • Eye pain [Hersh and Fox, 2014]

      • Vision problems/optic neuritis [NMSS Kurtzke FSS, 2018]
      low asterisk Constitutional symptom, therefore separated from functional systems. Note: (N = 3,857; Q10).
      Responses were recoded to facilitate interpretation. Means were calculated for continuous variables and percentages for categorical variables. Chi-square tests were used to evaluate relapse frequency and topics discussed by frequency of patient-HCP engagement during relapse as well as patient satisfaction by timing of HCP follow-up after the patient's initial reporting of the relapse  (≤ 1 month versus > 1 month). Results were rounded to 1 significant figure; as a result, they do not always sum to 100% [

      Data on file. Health Union, LLC. 2017.

      ; Results on file, Mallinckrodt Pharmaceuticals, 2018].

      4. Results

      4.1 Patient demographics and MS characteristics

      The demographics of all patients who completed the survey are shown in Table 2. The mean age was 51.2 years, with the largest proportion of patients being ages 40–59 years; most were female (84.3%) and Caucasian (89.3%).
      Table 2Demographics, employment status, and health insurance characteristics.
      Note: N = 5,311 unless otherwise noted. The Question number (Q) noted in each section indicates the pertinent survey question listed in the Appendix.
      In terms of employment status, the largest proportion of patients reported being on disability (40.1%), followed by those actively employed (35.1%). Almost all (96.8%) had some form of health insurance. Patients were distributed across the United States, as shown in Fig. 1.
      Fig 1
      Fig. 1Geographic distribution of patients. Proportion of MSIA 2017 patients who dwelled in different regions of the U.S. (N = 4,454; Q6).
      Table 3 shows the MS-related characteristics of those surveyed. Relapsing-remitting MS was the most common MS diagnosis (72.2%), followed by secondary progressive MS (SPMS 12.1%) and primary-progressive MS (PPMS 9.3%); 6.5% did not know or recall the type of MS. Most (74.8%) patients who did not report a diagnosis of PPMS (n = 4,819) were using DMTs. Based on their response to the PDDS, patients were most often moderately (49.7%) or mildly (36.2%) disabled. Among patients who experienced MS-related symptoms within the previous month, symptoms that most affected their daily function were fatigue (31.1%), walking/balance/coordination problems (20.2%), and cognitive dysfunction (11.0%). For their MS care, most patients (88.4%) reported currently seeing a general neurologist or a neurologist who specialized in MS.
      Table 3MS-related characteristics.
      Note: N = 5,311 unless otherwise noted. The Question (Q) number noted in each section indicates the pertinent survey question listed in the Appendix.
      *See Materials and Methods for explanation of severity level determination using PDDS.

      4.2 MS relapse-related findings

      A total of 73.1% of patients (n = 3,882) reported experiencing at least 1 relapse in the 2 years preceding the survey; the median number of relapses reported was 2. The annualized relapse distribution for all patients was: 44.1% with < 1 relapse, 35.5% with 1–2 relapses, and 20.2% with > 2 relapses (Fig. 2). Relapse duration was reported as <1 month by 62.5% of patients, whereas 24.5% reported their relapse duration exceeded 1 month (i.e., 10.9% reported 1–2 months, 13.6% reported > 2 months); 12.9% were unsure, as shown in Fig. 3.
      Fig 2
      Fig. 2Proportion of patients with MS relapse during 1 year (annualized). Proportion of patients who had < 1, 1–2, or> 2 relapses before the survey (N=5,311; Q12).
      Fig 3
      Fig. 3Duration of average MS relapse. Proportion of patients whose relapse duration was < 1 month, 1–2 months, or > 2 months (N=3,882; Q13).
      Of the 10 leading symptoms during relapse (Fig. 4), the most common was fatigue (77.4% of patients), followed by numbness or tingling (70.0%), walking or balance issues (68.8%), muscle weakness (61.4%), cognitive dysfunction including memory loss, difficulty concentrating, and brain fog (58.8%), muscle spasms (56.7%), pain (54.8%), loss of coordination (53.5%), depression (49.6%), and heat sensitivity or intolerance (49.5%).
      Fig 4
      Fig. 4Ten leading symptoms experienced with MS relapse. Proportion of patients who experienced the 10 most common relapse symptoms during their MS relapses. The graph presents the 10 leading symptoms in descending order of frequency (N=3,882; Q14).
      The leading functional system affected by relapse was the sensory system (86.6%) (Fig. 5). In 70%−80% of patients, the cerebellar (79.1%), pyramidal (78.7%), cerebral (74.7%), and brainstem systems (70.2%) were affected; fatigue affected 77.9% of patients. Bladder/bowel and visual functional systems were affected in 53.7% and 43.1% of patients, respectively.
      Fig 5
      Fig. 5Leading functional systems affected by MS relapse. Distribution of symptoms among patients who experienced relapse preceding the survey by functional system, shown as percent of patients affected. (N = 3,857; Q10). .
      As shown in Table 4, moderate positive correlations were observed between pyramidal and cerebellar functional systems (rtet= 0.64), cerebral and brainstem systems (rtet= 0.57), and fatigue and the cerebral functional system (rtet= 0.56). Correlations between brainstem and sensory (rtet= 0.49), brainstem and cerebellar (rtet= 0.49), and sensory-pyramidal (rtet= 0.49) approached moderate levels, while other correlations indicated weaker positive relationships.
      Table 4Correlation between functional systems affected during MS relapse.
      ***Blue: No correlation; Purple: Weak correlation; Green: Moderate correlation.
      Note: (N = 3,857; Q10).

      4.3 Patient-HCP engagement

      As shown in Fig. 6, less than half (46.9%) of patients reported always/often contacting their HCP during relapse, and more than half (53.1%) engaged their HCP sometimes (27.3%), rarely (18.5%), or never (7.3%) during relapse.
      Fig 6
      Fig. 6Proportion of patients who engage their HCP during relapse. Percent of patients who engage their HCP during relapse grouped by frequency of engagement: always/often, sometimes, rarely, and never (N=3,882; Q15).
      A higher percentage of patients with < 1 relapse in 1 year (29.9%) was seen among patients who always/often engaged their HCP during relapse, vs. sometimes (19.2%) or rarely/never (16.7%). A higher percentage of patients with > 2 relapses in 1 year were seen among those who rarely/never (36.1%) engaged their HCP during relapse vs. those who did so sometimes (32.3%) and always/often (20.9%). Similar percentages of patients with 1–2 relapses, ranging from 47.3% to 49.2%, were seen among patients who engaged their HCP during relapse always/often, sometimes, and rarely/never (Fig. 7).
      Fig 7
      Fig. 7Frequency of HCP engagement during relapse by annualized relapse frequency. Percent of patients experiencing< 1, 1–2, or> 2 relapses in 1 year who engage their HCP always/often, sometimes, or rarely/never during relapse (N=3,882; Q12, Q15).
      The most common reasons for not engaging their HCP during relapse are shown in Fig. 8 (N = 2,931). The leading reason cited by 57.9% of patients was that the relapse was not severe enough to warrant HCP engagement. Other reasons provided were: the HCP was either unhelpful or didn't tell the patient to contact them during relapse (30.9%), relapse medications were not effective or tolerable (25.6%), patient preference to manage the relapse alone (24.4%), financial or insurance barriers that affected HCP engagement (16.1%), or relapse medication on hand already (10.0%).
      Fig 8
      Fig. 8Most common reasons reported by patients for not always contacting their HCP during relapse. The most common reasons that patients did not always contact their HCP during relapse, and the percent of patients who cited this reason (N=2,931; Q16).
      Relapse symptoms and severity, followed by relapse treatments, treatment effectiveness in resolving relapse, and satisfaction with relapse treatment were the most to least common topics explored. A higher percentage of patients who always/often engage their HCP during relapse reported key topics that are typically discussed during the interaction, compared with those who engage their HCP less frequently during relapse (as shown in Fig. 9). For example, 72.2% of patients who always/often engage their HCP during relapse typically discuss relapse symptoms and severity during the interaction, compared with 62.7% of patients who sometimes engage and 46.8% who rarely engage their HCP. This same trend of diminishing frequency of discussion with diminishing frequency of HCP engagement during relapse was evident across the range of relapse-related topics reported: prescription treatments available for relapse, effectiveness of treatment options in relapse resolution, and satisfaction with the treatment's resolution of the relapse.
      Fig 9
      Fig. 9Relapse-related topics discussed with HCP by frequency of HCP engagement during relapse. Percent of patients who discussed relapse-related topics, by the frequency of HCP engagement during relapse: always/often, sometimes, or rarely (N=3,559; Q16, Q17).
      A similar trend was observed for MS-related topics that were not relapse-specific. A larger percentage of patients who always/often engage their HCP during relapse discussed the topics of potential changes to their overall MS treatment plan and advancement or worsening of their MS more often than those who sometimes or rarely engage their HCP during relapse (data not shown). The number of topics discussed during patient-HCP engagement during the relapse was associated with the frequency of HCP engagement during relapse. For example, the average number of topics discussed was highest for those who always/often engage their HCP during relapse (5.2 topics), compared with those who sometimes engage their HCP (4.1 topics) and those who rarely engage their HCP (2.9 topics).
      Among all patients who engaged with their HCP during relapse (i.e. always, often, sometimes, or rarely; N = 3,318), 35.0% of patients reported their HCP followed up within 1 month of initial contact about the relapse. Approximately 50% (50.3%) reported follow-up at the next office visit (either a follow-up visit or the next scheduled office visit), and 14.7% reported no HCP follow-up (Fig. 10). Patients whose HCPs followed up within 1 month of initial contact about the relapse (N = 1,160) were more likely to be satisfied with their HCP and their MS treatment plan than patients who were not contacted by their HCP within 1 month of initial contact for their relapse (χ² = 88.3 and χ² = 71.3; df = 1 and P < 0.001 for both).
      Fig 10
      Fig. 10HCP follow-up after initial contact for relapse. Percent of patients who engaged with their HCP during relapse and who reported that their HCP followed up. Timing of HCP follow-up (≤ 1 month, at next office visit, no follow-up) after being engaged by the patient during relapse, from time of first contact by the patient for the relapse (N = 3,318; Q18).

      5. Discussion

      The patient perspective has become increasingly important in research because it helps identify important factors from patients’ health experiences, results that are more relevant to the broader understanding of living with a chronic health condition, and other key insights [
      • Johnson D.S.
      • Bush M.T.
      • Brandzel S.
      • Wernli K.J.
      The patient voice in research–evolution of a role.
      ]. The voice of the patient should serve as a critical component and driver of research. In MS in particular, patient-focused research has become common and is used to glean insights and information that may be lost or omitted when the focus is more restricted, i.e., when studies are determined solely by traditional clinical endpoints or clinically driven evaluations [
      • Nickerson M.
      • Cofield S.S.
      • Tyry T.
      • Salter A.R.
      • Cutter G.R.
      • Marrie R.A.
      Impact of multiple sclerosis relapse: the NARCOMS participant perspective.
      ]. Voice of patient research in this context provides a broader understanding about the experience of patients with MS and their healthcare-seeking behavior and perceptions during relapse, which may challenge currently thinking (e.g., regarding relapse prevalence or duration).
      The general similarity of the demographic parameters of the MSIA 2017 patients and published MS cohorts highlights its representativeness of the larger MS population within the United States in terms of gender, age, race, and geography [
      • Nickerson M.
      • Cofield S.S.
      • Tyry T.
      • Salter A.R.
      • Cutter G.R.
      • Marrie R.A.
      Impact of multiple sclerosis relapse: the NARCOMS participant perspective.
      ,
      • Noonan C.W.
      • Williamson D.M.
      • Henry J.P.
      • et al.
      The prevalence of multiple sclerosis in 3 US communities.
      ,
      • Dilokthornsakul P.
      • Valuck R.J.
      • Nair K.V.
      • Corboy J.R.
      • Allen R.R.
      • Campbell J.D.
      Multiple sclerosis prevalence in the United States commercially insured population.
      ]. This study included patient types not often captured in MS research, as seen by the varied employment status and health insurance coverage; 64.1% were not actively working and 39.9% had Medicare or Medicaid insurance. In contrast with the more-frequently evaluated commercially insured MS population captured in many MS studies, which is likely younger, healthier and employed, MSIA 2017 may reflect often underrepresented patient subgroups. Our study lends important insights from a large, diverse, real-world sample of patients with MS, from an online MS community [Cohen et al., 2012]. Important insights were uncovered, providing helpful and potentially actionable opportunities to inform MS care practices.
      • I.
        Relapses remain a challenge for MS patients. Currently, most MS studies report mean annualized relapse rates, which typically reflect too brief an observation time and therefore underestimate relapse frequency. As well, most studies do not look at measures of relapse severity, such as associated duration or symptoms. In our study, almost 75% of patients who were eligible for maintenance therapy (DMTs) reported currently taking it. Specific DMTs used were not further queried nor were medication compliance details. However, approximately 20% of MS patients reported having had > 2 relapses in 1 year, almost 25% reported relapse lasting more than 1 month, and more than 2/3 experienced serious relapse symptoms which may incur further health risks. For example, walking/balance/coordination issues affected 68.8% of patients during relapse and could potentially lead to falls. Where higher baseline disability was seen (63.8% had moderate to severe disability), additional impacts of relapse would be detrimental to the patient, especially if underreported.
      • II.
        Over 50% of patients who experienced relapses said that they contact their HCP sometimes (27.3%), rarely (18.5%), or never (7.3%) during relapse. Although relapses are heterogenous and do not always require treatment per NMSS, over 25% of patients reported rarely or never contacting their HCP during relapse [
        National Multiple Sclerosis Society
        Managing Relapses.
        ;
        • Emrich L
        When to report MS relapses to your doctor.
        ]. Lack of HCP engagement during relapse can impact critical exchange of detail and timely assessment of the relapse to corroborate severity, determine appropriate treatment, and assess longer-term changes as needed. Lack of engagement may further preclude the opportunity to discuss treatment options that are suitable, effective, and enhance likelihood of prompt relapse recovery.
      • III.
        Reasons for not engaging one's HCP during relapse warrant investigation. Approximately 58% of patients felt their relapse was not severe enough for HCP engagement. This is in contrast to the serious relapse symptoms reported by large percentages of patients, such as walking/balance/coordination issues (68.8%), muscle weakness (61.4%), cognitive dysfunction including memory loss, difficulty concentrating, and brain fog (58.8%), and loss of coordination (53.5%), among others. Our analysis of functional systems impacted by relapse indicated pyramidal and sensory systems (> 85% of patients) occurred more often than visual and bladder/bowel systems impacts (43% and 53% of patients, respectively). Relapse symptoms impacting cerebellar systems in 79% of patients are concerning as they can lead to serious bodily injury (e.g., falls, fractures); as such, they should be of considerable concern to patients, their doctors, and the healthcare system. This is in contrast to the most commonly reported reason for not engaging one's HCP during relapse, i.e. that the relapse was not severe enough. Patients may not perceive their symptoms to be severe, but they may not be able to evaluate and/or recognize the full scope or severity of symptoms present or they may feel reluctant to communicate certain symptoms to their HCP [
        • Tintoré M.
        • Alexander M.
        • Costello K.
        • et al.
        The state of multiple sclerosis: current insight into the patient/health care provider relationship, treatment challenges, and satisfaction.
        ]. HCP engagement and open discussion are critical in evaluating and confirming relapse and assessing the implications for patient care. Absence of these key touchpoints may further adversely affect the patient-HCP bond by encouraging misconceptions about the value of care and available treatment options and by limiting communication vital to successful management of the individual disease course.
      • IV.
        As well, moderately positive correlations between pyramidal and cerebellar systems and between brainstem and cerebral systems suggest certain functional system impacts of relapse occurred together (e.g., muscle spasms and balance; speech difficulties and cognitive dysfunction). These correlations may be helpful for providers and may facilitate the explicit evaluation of symptoms that may be more likely interrelated. This highlights the importance of timely, transparent, and thorough patient-HCP dialogue when assessing symptoms, severity, and impact of relapse.
      • V.
        Patients experiencing the lowest number of relapses in 1 year were most prevalent among those that always/often engaged their HCP during relapse, and patients experiencing the highest number of relapses in 1 year were most prevalent among those who rarely/never engaged their HCP during relapse. There may be an inherent association between patients who relapse less often and severity, disease control, and/or medication compliance. HCP engagement would likely improve the probability and robustness of relapse understanding, assessment, and subsequent treatment selection and provide an opportunity for broader care modifications regarding maintenance therapy. The proportion of patients with the most relapses who rarely/never engaged their HCP during relapse warrants further exploration, as it may reflect patients who are disengaged but have important unmet needs.
      A higher proportion of patients who more frequently engage their HCP during relapse reported discussion of relapse-related and MS-related (non-relapse-specific) topics during engagement. Frequency of patient-HCP engagement during relapse was also associated with the number of topics discussed. The topics most commonly covered were relevant to the acute relapse (e.g. relapse symptoms and severity, relapse treatments). Topics less commonly covered were more important for broader and ongoing care (e.g., treatment effectiveness in resolving relapse, satisfaction with relapse treatment, potential changes to the overall MS treatment plan, and advancement or worsening of their MS). Considering this, timely and comprehensive patient-HCP discussion is clearly integral during relapse.
      VI. HCP follow-up within 1 month of initial patient outreach about the relapse was key in ensuring satisfaction. While only 35% of patients reported HCP follow-up within 1 month of their reporting the relapse, such timely follow-up was significantly associated with increased patient satisfaction with both the HCP and the overall MS treatment plan. HCP follow-up after relapse may help to ensure relapse resolution, account for considerations for future relapses (understanding the patient's experience and treatment effectiveness during the specific relapse), and improve the patient-HCP relationship. Timely feedback regarding treatment dissatisfaction, tolerability, or effectiveness may warrant and inform future discussions and treatment considerations [
      • Emrich L
      When to report MS relapses to your doctor.
      ,
      • Stoppe M.
      • Busch M.
      • Krizek L.
      • Bergh F.T.
      Outcome of MS relapses in the era of disease-modifying therapy.
      ].
      A recent survey study of both MS patients and HCPs (primarily neurologists) which examined the patient-HCP relationship and communication therein found that inherent challenges exist in communication and perceptions of the HCP and the patient [
      • Tintoré M.
      • Alexander M.
      • Costello K.
      • et al.
      The state of multiple sclerosis: current insight into the patient/health care provider relationship, treatment challenges, and satisfaction.
      ]. Approximately 18–20% of patients reported being uncomfortable speaking about difficulty walking, tremors, and muscle spasms, with “sensitive symptoms” posing far more discomfort, e.g., sexual difficulties (54%), bladder/bowel problems (28%), mood swings (26%), difficulty swallowing (21%), and cognitive/memory issues/trouble concentrating (21%). Only 2%–3% of neurologists identified symptoms such as difficulty in walking, tremors, and spasms as uncomfortable topics for their patients; however, they overestimated patients’ discomfort talking about the “sensitive symptoms,” including sexual difficulties (87%), bladder/bowel problems (54%), mood swings (37%), and cognitive/memory issues/trouble concentrating (37%). As well, the study found that openness of patient-physician dialogue positively affected patient satisfaction with MS-related treatment and outcomes. In the present study, the greater number of discussion topics among patients who always/often engage their HCP during relapse would be a similar indicator of such openness. A strong patient-HCP relationship backed by trust and patient-centric care would clearly be key to overcoming such barriers.

      6. Limitations

      Data collected by online surveys represent convenience samples, which are subject to participation bias. Patients may therefore not be generalizable to the larger MS population. Nevertheless, as described, the demographics of the MSIA 2017 survey population fell within the ranges of other published studies, with some important underserved subgroups also represented herein. Given the cross-sectional survey design, causality cannot be established.
      Currently, there are no validated instruments for evaluating MS relapse. The lack of validated instruments may have affected comprehension and interpretation of items by survey participants [
      National Multiple Sclerosis Society
      Clinical Study Measures.
      ]. Lack of validated instruments should not preclude the exploration of important research questions. Health Union and members of their patient community were involved in evaluating and structuring questions to increase clarity, simplicity, and conciseness to mitigate these issues.
      Our study is subject to recall bias. For the MSIA 2017 survey, a reference period of 2 years before the survey was used for questions pertaining to relapse occurrence and relapse symptoms. Although this is a lengthy reference period, prior studies have shown relapses are more likely to occur during this timeframe vs. a shorter one. Thus using a 2-year recall period may ensure richer insights into patient experiences with MS relapse. In addition, a 2-year reference period has been used by several other studies involving patient recall [
      • Kalincik T.
      Multiple sclerosis relapses: epidemiology, outcomes and management: a systematic review.
      ].
      Patients may have misclassified relapses (e.g., pseudo-relapses), potentially more so if not engaging with their HCP sufficiently. This misclassification risk would be present in most patient-survey research. However, the high proportion of insured patients at more advanced stages of disease, per the MS disability status and age, may indicate patients with longer durations of disease who are more knowledgeable about their disease and thereby minimize such a risk.
      Similarly, patient-reported symptoms in this study may have differed in breadth and severity than if they were clinically confirmed or clinically observed symptoms. Other studies have included patient-reported symptoms as well, realizing that there is a value to the patient perspective, considering that symptoms inadvertently can be overlooked or potentially underreported by patients to their HCPs. While our findings on functional systems impacted by relapse generally agree with those of prior studies (where symptoms may have been clinically observed, patient-reported and subsequently clinically confirmed, or only patient-reported), this study shares specific methodology for categorization of relapse symptoms into functional systems [
      • Kalincik T.
      • Buzzard K.
      • Jokubaitis V
      Risk of relapse phenotype recurrence in multiple sclerosis.
      ,
      • Stoppe M.
      • Busch M.
      • Krizek L.
      • Bergh F.T.
      Outcome of MS relapses in the era of disease-modifying therapy.
      ]. Prior ambiguity in this categorization may help to explain differences in results, as would the heterogenity of patients in each study.
      HCP follow-up within 1 month of initial contact by the patient about relapse was evaluated as a specific factor in patient satisfaction. Both patients and HCPs have a role to play in taking initiative on timely communications following relapse, with regard to relapse resolution, effectiveness and/or tolerability of treatment, or other considerations. A timeframe of 30 days was chosen since relapses are defined using a 30-day reference period to distinguish them from a prior relapse [
      National Multiple Sclerosis Society
      Managing Relapses.
      ]. However, several different steps can take place during a relapse, and the time associated with each step (e.g., initiation of the relapse, contact or visit with the HCP, and receipt and completion of relapse treatment) may mean that the length of such a window is variable or longer than 30 days. Investigation into appropriate adaptation for clinical practice should be considered.

      7. Conclusions

      Given the challenges in understanding the frequency and severity of MS relapse and healthcare-seeking behavior during relapse, this study contributes valuable insights from an online MS community in the United States. It confirms that rate, duration, and symptoms of relapse vary for MS patients, with some patients definitively experiencing higher disease activity than others. Subgroups that are particularly affected that have been identified in this study include those who experienced > 2 relapses in 1 year (20.2%), with relapse duration of ≥ 1 month (24.5%), and relapse symptoms that posed challenges to daily functioning as well as risks of further adverse consequences.
      Although timely and appropriate treatment of relapse is associated with a short-term benefit to the speed of functional recovery from relapse and mitigation of residual deficits, more than 50% of patients reported not regularly engaging their HCP during relapse. Approximately 25% of patients engage their HCP rarely or not at all during relapse. Inherent difficulties already exist when it comes to patient-HCP communication and transparency, as past research shows. As these study results highlight, fewer relapses coincide with more HCP engagement and more HCP engagement is associated with increased discussion of MS- and relapse-related topics, leading to improved disease management.
      Among patients who engage their HCP during relapse, almost 2/3 of patients reported not receiving follow-up within 1 month of initial HCP contact about the relapse. Timely HCP follow-up is associated with greater patient satisfaction with the MS care provider and the MS treatment plan. Patient outreach by the HCP and/or their care team to better understand the outcome of the relapse would be beneficial. This could also be a means to connect with patients who might otherwise be lost to the HCP and possibly the healthcare system, to strengthen the patient-HCP relationship, and to alter the trajectory of the individual's MS care.
      To enhance the patient-HCP MS care partnership and patient outcomes, clear parameters driving engagement during relapse and during follow-up after relapse should be identified and prioritized. Benefits may be realized from doing so. Further insights into the decision-making behavior as well as the assumptions of patients and HCPs are needed to continue to inform development of effective management strategies.

      Author conflict statements

      Tara Nazareth: Tara Nazareth was an employee and stockholder of Mallinckrodt Pharmaceuticals at the time of this research.
      Andrew Rava: Andrew Rava was a contractor at Mallinckrodt Pharmaceuticals at the time of this research and does not own Mallinckrodt stock.
      Jackie Polyakov: Jackie Polyakov is currently an employee of Mallinckrodt Pharmaceuticals.
      Edward Banfe: Edward Banfe is currently an employee of Mallinckrodt Pharmaceuticals and owns Mallinckrodt stock.
      Royce W. Waltrip II: Royce W. Waltrip II is currently an employee of Mallinckrodt Pharmaceuticals and owns Mallinckrodt stock.
      Kristine Zerkowski: Kristine Zerkowski is an employee of Health Union.
      Leslie B. Herbert: Leslie B. Herbert is an employee of Health Union.

      Funding statement

      Mallinckrodt Pharmaceuticals is the sponsor and sole funder of the research study. Health Union was responsible for the collection of the data and both Health Union and Mallinckrodt were responsible for the analysis and interpretation of the data from Health Union's multiple sclerosis patient survey. Mallinckrodt funded the writing, and both parties decided to collaborate and to submit the manuscript to Multiple Sclerosis and Related Disorders.

      Acknowledgements

      The authors thank Fern Alexander, PhD, for medical writing services and conceptual contributions and Esther Tazartes, MS, for editing services, which were funded by Mallinckrodt Pharmaceuticals.

      Appendix 1. MSIA 2017 Survey Questions Utilized in the Study. Appendix Legend

      This is an abridged version of Health Union's proprietary Multiple Sclerosis in America (MSIA) 2017 survey instrument that contains only those survey questions utilized for this analysis. Use of this survey is prohibited without the express written consent of Health Union, LLC.
      Tabled 1
      Question 1
      What is your gender?
      ○ Female
      ○ Male
      ○ Other
      Tabled 1
      Question 2
      What best describes your race/ethnicity? If you prefer not to answer, simply select that option.
      ○ White/Caucasian
      ○ Black/African-American
      ○ Hispanic/Latino
      ○ Asian/Pacific Islander
      ○ Native American
      ○ Multiracial
      ○ Other
      ○ Prefer not to answer
      Tabled 1
      Question 3
      What is your age?
      <Drop down menu with options “Under 18” to “75 or older”>
      “Under 18″ = TERMINATE
      Tabled 1
      Question 4
      What best describes your employment status?
      ○ Employed, full time
      ○ Employed, part time
      ○ Self-employed
      ○ Unemployed, looking
      ○ Unemployed, not looking
      ○ On disability
      ○ Fully retired
      ○ Student
      ○ Do not work outside the home/Stay-at-home parent
      Tabled 1
      Question 5
      What best describes your health insurance?
      ○ Group coverage, through my employer or the employer of a spouse or family member
      ○ Private insurance, purchased directly from the insurance company
      ○ Health insurance exchange, enrolled through Affordable Care Act
      ○ Medicare
      ○ Medicaid
      ○ Military coverage, VA, or government employee insurance
      ○ Other insurance type/Not sure of what type
      ○ I do not have/I'm unsure if I have health insurance
      Tabled 1
      Question 6 (Optional)
      What is your five-digit zip code?
      Tabled 1
      Question 7
      What type of MS are you CURRENTLY diagnosed with?
      ○ Relapsing-remitting (RRMS)
      ○ Primary-progressive (PPMS)
      ○ Secondary-progressive (SPMS)
      ○ I don't know or I don't recall
      Tabled 1
      Question 8
      Are you currently using, or have you ever used, the following medications for management of your MS?
      ONLY DISPLAY BRANDED TREATMENTS HEARD OF
      Tabled 1
      Never usedUsed in the past, but no longer useCurrently use
      AUBAGIO® (teriflunomide)
      AVONEX® (interferon beta-1a)
      BETASERON® (interferon beta-1b)
      COPAXONE® (glatiramer acetate)
      GILENYA® (fingolimod)
      Glatopa™ (glatiramer acetate)
      LEMTRADA® (alemtuzumab)
      OCREVUS® (ocrelizumab)
      PLEGRIDY™ (peginterferon beta-1a)
      Rebif® (interferon beta-1a)
      RITUXAN® (rituximab)
      TECFIDERA® (dimethyl fumarate)
      TYSABRI® (natalizumab)
      ZINBRYTA™ (daclizumab)
      Other disease-modifying treatment (DMT)
      Tabled 1
      Question 9 [MS Patient-Determined Disease Steps (PDDS)]
      Please read the choices listed below and choose the one that best describes your own situation.
      ○ I may have some mild symptoms, mostly sensory due to MS, but they do not limit my activity. If I do have an attack, I return to normal when the attack has passed.
      ○ I have some noticeable symptoms from my MS, but they are minor and have only a small effect on my lifestyle.
      ○ I don't have any limitations in my walking ability. However, I do have significant problems due to MS that limit daily activities in other ways.
      ○ MS does interfere with my activities, especially my walking. I can work a full day, but athletic or physically demanding activities are more difficult than they used to be. I usually don't need a cane or other assistance to walk, but I might need some assistance during an attack.
      ○ I use a cane, a single crutch, or some other form of support (such as touching a wall or leaning on someone's arm) for walking all the time or part of the time, especially when walking outside. I think I can walk 25 feet in 20 seconds without a cane or crutch. I always need some assistance (cane or crutch) if I want to walk as far as 3 blocks.
      ○ To be able to walk 25 feet, I have to have a cane, crutch, or someone to hold on to. I can get around the house or other buildings by holding on to furniture or touching the walls for support. I may use a scooter or wheelchair if I want to go greater distances.
      ○ To be able to walk as far as 25 feet, I must have 2 canes, crutches, or a walker. I may use a scooter or wheelchair for longer distances.
      ○ My main form of mobility is a wheelchair. I may be able to stand and/or take one or two steps, but I can't walk 25 feet, even with crutches or a walker.
      ○ I am unable to sit in a wheelchair for more than one hour.
      Tabled 1
      Question 10
      Ask if experienced symptoms within the past 3 months; Display selected symptoms from past 3 months
      Which symptom affects your ability to function in your daily life the most?
      ○ Anxiety
      ○ Bladder problems
      ○ Bowel problems
      ○ Cognitive dysfunction (memory loss, difficulty concentrating, brain fog)
      ○ Cold sensitivity/intolerance
      ○ Depression or mood changes
      ○ Dizziness/vertigo/lightheadedness
      ○ Eye pain
      ○ Fatigue
      ○ Foot drop
      ○ Hearing loss/issues
      ○ Headaches/migraines
      ○ Heat sensitivity/heat intolerance
      ○ Loss of coordination
      ○ Muscle spasms/spasticity
      ○ Muscle weakness
      ○ Numbness, tingling, or other altered sensations (eg, “pins and needles”)
      ○ Pain
      ○ Paralysis
      ○ Sensitivity to sound
      ○ Sexual dysfunction
      ○ Speech difficulties
      ○ Tremors
      ○ Trouble swallowing
      ○ Vertigo
      ○ Vision problems/Optic neuritis
      ○ Walking/balance/coordination problems
      ○ Other symptom (not listed)
      Tabled 1
      Question 11
      Display selected HCPs ever seen for MS
      What type of healthcare professional CURRENTLY treats you specifically for your MS?
      ○ Ophthalmologist or neuro-ophthalmologist (Eye doctor)
      ○ Neurologist specializing in MS
      ○ General neurologist
      ○ Primary care physician/Family physician/Internal medicine physician
      ○ Nurse practitioner/Physician assistant
      ○ Radiologist
      ○ Emergency room (ER) physician
      ○ Alternative/holistic medicine specialist
      ○ Pain management doctor
      ○ Physical/speech/occupational therapist
      ○ Orthopedist
      ○ Psychologist
      ○ Gastroenterologist
      ○ Urologist
      ○ Clinical researcher
      ○ Dietician/nutritionist
      ○ Other healthcare professional
      ○ I don't currently see a healthcare professional for my MS
      Tabled 1
      Question 12
      Over the past 2 years, how many MS relapses/exacerbations have you experienced?
      <Drop-down menu with options ranging from “0″ to “40″, then “More than 40″>
      Tabled 1
      Question 13
      How long does a relapse/exacerbation last on average for you?
      ○ Less than 1 week
      ○ 1 up to 2 weeks
      ○ 2 weeks up to 1 month
      ○ 1 to 2 months
      ○ 3 up to 6 months
      ○ 6 up to 9 months
      ○ More than 9 months
      ○ Unsure/don't recall
      Tabled 1
      Question 14
      What symptoms have you experienced with your relapses/exacerbations over the past 2 years? (Select all that apply)
      □ Anxiety
      □ Bladder problems
      □ Bowel problems
      □ Cognitive dysfunction (memory loss, difficulty concentrating, brain fog)
      □ Cold sensitivity/intolerance
      □ Depression or mood changes
      □ Dizziness/vertigo/lightheadedness
      □ Eye pain
      □ Fatigue
      □ Foot drop
      □ Hearing loss/issues
      □ Headaches/migraines
      □ Heat sensitivity/heat intolerance
      □ Loss of coordination
      □ Muscle spasms/spasticity
      □ Muscle weakness
      □ Numbness, tingling, or other altered sensations (eg, “pins and needles”)
      □ Pain
      □ Paralysis
      □ Sensitivity to sound
      □ Sexual dysfunction
      □ Speech difficulties
      □ Tremors
      □ Trouble swallowing
      □ Vertigo
      □ Vision problems/Optic neuritis
      □ Walking/balance/coordination problems
      □ Other symptom (not listed)
      Tabled 1
      Question 15
      How often do you talk with or visit your doctor/healthcare professional when you are having a relapse/exacerbation?
      ○ Never
      ○ Rarely
      ○ Sometimes
      ○ Often
      ○ Always
      Ask if did not select “Always” for discussions with HCP when having a relapse/exacerbation
      Tabled 1
      Question 16
      Why do you not always contact your doctor/healthcare professional when you have a relapse/exacerbation? (Select all that apply)
      □ My relapses/exacerbations are not always severe enough to warrant it
      □ Financial/cost/insurance issues/don't have insurance
      □ My doctor/healthcare professional didn't tell me I should
      □ I don't find my doctor/healthcare professional to be helpful
      □ I prefer to manage my relapses/exacerbations on my own
      □ I have a prescription medication ready if I have a relapse/exacerbation
      □ I haven't found a treatment that works well for my relapses/exacerbations
      □ I can't tolerate most medication/treatments
      □ Other reason (please specify):_______
      Ask if contact HCP when having a relapse/exacerbation (Rarely, Sometimes, Often, Always)
      Tabled 1
      Question 17
      When you are speaking with your doctor/healthcare professional about relapse/exacerbation, what is typically discussed? (Select all that apply)
      □ Symptoms/severity of the relapse/exacerbation
      □ Duration of the relapse/exacerbation
      □ Frequency of relapse/exacerbation
      □ Prescription medications/medical treatments available for relapse/exacerbation
      □ Other (non-prescription medication) treatment options for relapse/exacerbation (eg, rehab, vitamins, rest, etc.)
      □ Effectiveness of treatment options in resolving relapse/exacerbation
      □ Overall satisfaction with medication or treatment received to resolve relapse/exacerbation
      □ Potential change in overall MS treatment plan
      □ Advancement of MS or worsening of disease
      □ Residual disability or incomplete resolution of symptoms
      □ When to contact them when I'm having a relapse/exacerbation
      □ Other (please specify):_______
      Ask if they ever used any treatment for relapse/exacerbation
      Tabled 1
      Question 18
      When does your doctor or healthcare team follow-up with you about your relapse/exacerbation?
      ○ 1 to 2 weeks after my initial contact with them about my relapse/exacerbation
      ○ 2 weeks to a month after my initial contact with them about my relapse/exacerbation
      ○ At a follow-up office visit
      ○ At my next scheduled/routine office visit
      ○ They usually don't

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