Пациентский опыт Myelin Oligodendrocyte Glycoprotein Antibody-Associated Beacy: качественные пациенты и клинические интервью, информирующие о разработке концептуальной модели.

Key Summary Points

Why carry out this study
Currently, little is known about the key symptoms and health-related quality of life (HRQoL) impacts of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) from the patient perspective This non-interventional study sought to explore the patient experience of MOGAD through patient and clinician qualitative concept elicitation interviews to develop a conceptual model of MOGAD
What was learned from this study
The final conceptual model shows the breadth of MOGAD symptoms and their impact Key symptoms reported by patients were eye pain, fatigue, body aches/pain, headaches, and blurred vision; and key HRQoL impacts reported by patients were difficulty with carrying out household chores, inability to work, depression, and difficulty walking The conceptual model and study findings may help inform future clinical trials to ensure that symptoms and HRQoL impacts most important to patients are addressed by treatments

Introduction

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare, autoimmune demyelinating central nervous system disease [ 1 – 4 ]. MOGAD affects men and women, and a higher incidence has been reported in children than in adults [ 4 , 5 ]. Epidemiological data are limited; however, estimated global incidence is between 0.16 and 0.34 per 100,000 people annually [ 4 , 6 – 9 ].

Common manifestations of MOGAD include optic neuritis (ON), transverse myelitis (TM), and acute disseminated encephalomyelitis (ADEM) [ 10 – 14 ]. MOGAD may occur as a single flare (monophasic) or recurrent flares (relapsing) [ 15 ]. MOGAD symptoms overlap with other neuroinflammatory diseases, such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), making diagnosis difficult [ 14 , 16 , 17 ]. The possibility of overlapping autoimmune encephalitis and MOGAD may also require consideration [ 18 , 19 ]. Although clinical diagnostic criteria for MOGAD have been published [ 4 ], treatment guidelines have not yet been established, and there are currently no approved treatments [ 1 ].

Due to the rarity of MOGAD and its recent establishment as a distinct disease entity, there is a paucity of in-depth, qualitative data on MOGAD signs, symptoms, and impacts on health-related quality of life (HRQoL) from the patient perspective. Qualitative research, including concept elicitation methods, can be a powerful method for gaining and understanding patient insights. Furthermore, qualitative research in the target population during medical product development is endorsed by the US Food and Drug Administration [ 20 ] and an important component of new pharmacometrics, such as multicriteria decision analysis, to ensure a fit-for-purpose clinical outcome assessment strategy [ 21 ]. Qualitative research on the patient experience of MOGAD could highlight unmet needs, inform future research, and optimize the value of potential therapeutic agents [ 22 – 24 ]. Data from qualitative research can be used to develop conceptual models of the patient experience of disease. Both specific concepts (including signs, symptoms, and disease impacts) and the relationships between those concepts are included within the model [ 25 , 26 ]. A conceptual model also includes hierarchization of concepts based on concept frequency and/or insights into which concepts have greatest impact to highlight those that are most proximal to the patient experience [ 25 , 26 ].

This study aimed to understand key concepts related to the patient experience of MOGAD. Concept elicitation interviews explored the symptoms and HRQoL impacts considered to be most bothersome/clinically relevant and most important to improve with treatment from the perspectives of patients and treating clinicians. Insights were used to refine a conceptual model of MOGAD, integrating findings from published literature and from the interviews.

Methods

Study Design Overview

Cross-sectional, semi-structured, qualitative concept elicitation interviews were conducted with adult patients with MOGAD and clinicians who specialized in the treatment and management of patients with MOGAD. Interviewed clinicians provided feedback on a preliminary conceptual model of MOGAD based on a targeted literature review. Findings from the clinician and patient interviews were used to refine the conceptual model.

Ethical Approval

This study was conducted in accordance with the Declaration of Helsinki, International Conference on Harmonization guidelines for Good Clinical Practice, and other current data-protection guidance. Ethical approval was provided by Western Copernicus Group Independent Review Board (IRB no. 20222224; valid from December 19, 2022, to May 2, 2023). Written informed consent was obtained from each patient and clinician prior to study participation.

Targeted Literature Review

Prior to the qualitative interviews, a targeted review of published qualitative literature was conducted. Searches were conducted in June 2021 via computerized bibliographic databases (MEDLINE ® , EMBASE™, and PsychINFO ® ). Search terms included keywords and Medical Subject Headings terms relating to the disease area (e.g., myelin oligodendrocyte glycoprotein, MOGAD) and qualitative research (e.g., interview, focus groups). Supplementary searches of Google Scholar and patient blogs/forums/stories were performed to provide further insight. No time limits were applied to searches. Abstracts identified were screened for eligibility (Appendix A1) and full-text review. Full-text articles were reviewed using inductive thematic analysis [ 25 ], allowing themes to be explored freely rather than searching for themes based on pre-existing theory. Coded data were extracted into a Microsoft Excel spreadsheet for analysis and data filtering. The literature review findings informed the development of the preliminary conceptual model and interview guides for the patient and clinician interviews (Fig.  1 ).

Overview of study methods. MOGAD, myelin oligodendrocyte glycoprotein antibody-associated disease

Qualitative Interviews

Participants

Patient eligibility criteria included: aged 18–89 years of age (inclusive) at the time of consent; had a history of relapsing MOGAD with at least one relapse in the previous 24 months (documented evidence or patient-report of relapse); had any of the following clinical presentations: ON (single, recurrent, or simultaneous bilateral), TM (including the longitudinally extensive TM), ADEM or MOG antibody-associated encephalitis, brain stem encephalitis, or combined presentations (e.g., ON + TM); and were MOG-IgG seropositive (confirmed via cell-based assay). Patients were required to be fluent in English and have the cognitive and linguistic capabilities to participate in a 60-min telephone interview (with breaks, if needed) to discuss their experience of MOGAD. Patients were excluded if they had concurrent autoimmune disease diagnoses (including MS and NMOSD) or were either taking part in or had taken part in a clinical trial for MOGAD in the 3 months prior to the study.

Given the qualitative nature of this study, no sample size calculation was conducted. Sample size was determined based on the principle of conceptual saturation (the point at which no new concept-relevant information is expected to emerge in further interviews) [ 27 ]. In homogeneous populations, saturation is typically achieved in 10–12 interviews [ 28 , 29 ]. Given the rarity of MOGAD, a sample size of 12 was deemed adequate.

Eligible clinicians had experience in the diagnosis, management, and treatment of patients with MOGAD, were fluent in English, and were willing and able to participate in a 60-min telephone interview to discuss the patient experience of MOGAD and provide feedback on the preliminary conceptual model.

Recruitment

Patients were recruited via independent clinicians and patient organizations. Patients were pre-screened; if criteria were met, patients were asked to provide evidence of their MOGAD diagnosis, any relevant eligibility criteria, and clinical characteristics. Evidence of eligibility was provided through a clinician-completed case report form (CRF) or through alternative evidence, which included a copy of the patient’s medical records stating both a clinician-confirmed diagnosis of MOGAD and MOG-IgG seropositivity (via a cell-based assay). Participating patients completed a demographic form to collect information on socio-demographic and clinical characteristics.

Clinicians were identified by the study sponsor and referred to the research team for selection in the study. Clinicians completed a screening form to collect information on demographic characteristics, clinical background, and experience in treating patients.

Qualitative Interviews

Patient and clinician interviews lasted 60 min and were conducted via Microsoft Teams. All interviewers were trained in qualitative research methods and had experience of conducting concept elicitation interviews. Semi-structured interview guides were used to guide discussions. Patient interviews were designed to explore the signs and symptoms of MOGAD and impacts on HRQoL. Open-ended questioning was first used to gain a spontaneous and unbiased response, followed by more targeted questioning to obtain further detail, where possible. Clinician interviews were designed to gain clinical insights on the signs, symptoms, and impacts experienced by patients and insights that could be applied to clinical trials (e.g., symptoms clinicians considered most important to assess in clinical trials). Clinicians also provided feedback on the preliminary conceptual model to determine the clinical relevance and comprehensiveness of the concepts included.

Data Analysis

Interviews were audio-recorded, transcribed verbatim, and identifiable information removed. Transcripts were analyzed using thematic analysis methods [ 25 ] and coded using ATLAS.ti software [ 30 ]. Themes were identified through inductive (directly from the data) and abductive (applying prior knowledge) inference [ 31 ]. A coding scheme ensured consistent application and grouping of codes across transcripts. Coded statements were classified into domains/concepts and a list of participant quotations for each domain/concept was generated. The principle of conceptual saturation was applied to the patient interviews. Transcripts were ordered chronologically, divided into three groups and findings were compared from each group of interviews (notably, the concepts that emerged from interviews) in an iterative fashion. Conceptual saturation was deemed to have been achieved for concepts that did not emerge in the last group of interviews only (i.e., emerged spontaneously in the prior two groups).

Results

Literature Review

Thirty-three abstracts were identified, of which five met eligibility criteria and were reviewed as full-text articles. In addition, four patient blogs were identified and included. Based on these sources, a preliminary conceptual model including 33 symptoms and 20 HRQoL impacts was developed.

Interview Participant Information

Patient Demographic and Clinical Characteristics

Patients ( N  = 12) had a mean age (minimum–maximum) of 36.2 (26–67) years, were predominantly women ( N  = 8/12) and were white ( N  = 5/12) or Black/African American ( N  = 5/12; Table  1 ). Four patients were unable to provide confirmation of their diagnosis via a clinician-completed CRF but provided alternative evidence of their MOGAD diagnosis. Therefore, clinical characteristics are only reported for eight patients (Table  1 ). TM was the most common manifestation ( n  = 6/8) and patients had experienced a relapse within 12 months ( n  = 5/8) or within 12–24 months prior to their interview ( n  = 3/8).

Table 1 Patient demographic and clinical characteristics Demographic characteristic Total ( N  = 12) Age, years  Mean (minimum–maximum) 36.2 (26–67) Sex, n  Female 8  Male 4 Ethnicity, n  Non-Hispanic, non-Latino, non-Spanish origin 12 Race, n  Asian 1  Black or African American 5  White 5  Other 1 Geographical location, n  USA 10  Canada 1  Australia 1 Highest level of education, n  Middle and high school (USA) a 1  College or associate degree (vocational or academic) 3  Undergraduate degree (bachelor’s, professional, or equivalent) 5  Graduate degree (master’s, doctorate, or equivalent) 3 Work status, n  Working full time (in paid job or as volunteer) 6  Working part time (in paid job or as volunteer) 2  Part-time student 1  Unable to work because of condition 2  Retired 1 Clinical characteristic Total ( N  = 8) b History of relapsing MOGAD, n  Past 0–12 months 5  Past 12–24 months 3 Optic neuritis-unilateral, n  Recurrent unilateral 1  Never experienced 7 Optic neuritis-bilateral, n  Recurrent bilateral 2  Never experienced 6 Transverse myelitis, n  Previously experienced in the past 6  Never experienced 2 MOGAD encephalomyelitis/brain stem encephalitis/ADEM, n  Currently experiencing 1  Previously experienced in the past 4  Never experienced 3 ADEM, acute disseminated encephalomyelitis; CRF, case report form; MOGAD, myelin oligodendrocyte glycoprotein antibody-associated disease a Grade 6–12; high school diploma/General Education Diploma or equivalent b Four patients were unable to obtain a clinician CRF and provided alternative evidence of a clinical diagnosis of MOGAD

Patient demographic and clinical characteristics

ADEM, acute disseminated encephalomyelitis; CRF, case report form; MOGAD, myelin oligodendrocyte glycoprotein antibody-associated disease

a Grade 6–12; high school diploma/General Education Diploma or equivalent

b Four patients were unable to obtain a clinician CRF and provided alternative evidence of a clinical diagnosis of MOGAD

Clinician Characteristics

Two clinicians were interviewed ( n  = 1 woman; n  = 1 man). Both clinicians were experienced US-based neurologists and worked in academic settings. One clinician had 5 years’ experience of managing and treating patients with MOGAD, and the other had 6 years’ experience. One clinician reported seeing five patients with MOGAD per month and the other 12 patients per month.

Interview Findings

Signs and Symptoms

Thirty-two symptoms were reported across seven domains (Fig.  2 ). All patients reported experiencing at least one constitutional symptom, with all patients reporting fatigue and most reporting body aches/pain ( N  = 11/12). All patients reported experiencing at least one visual symptom, with most patients reporting multiple visual symptoms, including eye pain ( N  = 12/12), blurred vision ( N  = 11/12), and flashes of light or auras ( N  = 9/12). Almost all patients reported experiencing at least one general neurological symptom ( N  = 11/12), most frequently headaches ( N  = 11/12) and speech difficulties ( N  = 9/12). Most patients reported experiencing at least one neurological sensory-motor symptom, most frequently weakness ( N  = 10/12), numbness/tingling ( N  = 10/12), and balance difficulties ( N  = 10/12). Genitourinary, gastrointestinal, and respiratory and chest-related symptoms were also reported, most frequently, urinary symptoms/difficulties ( N  = 8/12), bowel symptoms ( N  = 5/12), and chest symptoms ( N  = 4/12). Samples of patient quotes for the most frequently reported symptoms across each domain and for each symptom are provided in Table  2 and Supplementary Table S1 , respectively. Some patients also discussed the duration of their symptoms; for example, symptoms such as weakness, fatigue, body aches/pain, eye pain, loss of appetite, numbness/tingling, and urinary symptoms/difficulties were experienced by some patients constantly (Supplementary Table S2).

Signs and symptoms of MOGAD reported by patients and clinicians. MOGAD, myelin oligodendrocyte glycoprotein antibody-associated disease

Table 2 Overview of most commonly reported symptoms across each symptom domain with example quotes from patient interviews Symptom domain/concept No. of patients a Example quotes from patient interviews Constitutional  Fatigue 12/12 “I always wake up feeling like I haven't slept…even when I am sleeping and I'm in a period where I am sleeping much better, I'm still always exhausted and always tired” Visual  Eye pain 12/12 “It’s more of a sharp pain. So when you look, it’s like a needle in your eye” Neurological: general  Headaches 11/11 “It’s mostly just throbbing headaches in different locations” Neurological: sensory-motor  Weakness 10/10 “It [weakness] just kind of didn’t stop. And so we found that there was distinct weakness in the right side…so there's always present symptoms”  Numbness/tingling 10/10 “Baseline the numbness and tingling is always there…that feeling of…limbs falling asleep”  Balance difficulties 10/10 “I feel unsteady on my feet…and I guess there’s some fear with that kind of a day too ‘cause I worry about falling” Genitourinary  Urinary symptoms/difficulties 8/8 “The urgency and frequency [to urinate] is kind of just there all the time” Gastrointestinal  Bowel symptoms 5/6 “Sometimes I couldn’t even control it. Like I could get up to walk across the room and have diarrhea…wake up in the middle of the night with it, have it in my sleep. It was really—it was horrible” Chest-related, respiratory, and throat  Chest symptoms 4/4 “I do have these…pains in my chest. And like something was taken out of there and I just need a couple of minutes before I could regain full energy in that part of my body” Patient IDs are not included to maintain anonymity and avoid potential identification of patients from their combination of symptoms, but quotes in this table represent statements from five different patients a All patients did not report each symptom domain (italics). The denominator represents the total number of patients that reported the respective symptom domain

Overview of most commonly reported symptoms across each symptom domain with example quotes from patient interviews

Patient IDs are not included to maintain anonymity and avoid potential identification of patients from their combination of symptoms, but quotes in this table represent statements from five different patients

a All patients did not report each symptom domain (italics). The denominator represents the total number of patients that reported the respective symptom domain

MOGAD symptoms reported by clinicians aligned with those reported by patients. Two symptoms (light sensitivity and sexual dysfunction) were reported in the clinician interviews only (Fig.  2 ).

Patients reported that body aches/pain and eye pain were the most bothersome symptoms of MOGAD (both N  = 3/12) and the most important to improve with treatment (both N  = 3/12). Similarly, clinicians reported that body aches/pain would be the most important symptom to improve in patients with MOGAD; however, they did not specify whether they were referring to general pain or specific pain (e.g., visual pain or headaches).

HRQoL Impacts

Fifty HRQoL impact concepts across eight domains were reported by interviewed patients (Fig.  3 ). All 12 patients described impacts on emotional wellbeing, activities of daily living (ADL), physical functioning, and social functioning (Fig.  3 a). Almost all patients described impacts on work/school ( N  = 11/12), cognitive functioning ( N  = 11/12), and sleep ( N  = 10/12), and seven patients reported impacts relating to finances (Fig.  3 a). The most frequently reported HRQoL impacts were: difficulty carrying out household chores ( N  = 11/12); inability to work ( N  = 11/12); depression ( N  = 10/12); difficulty walking ( N  = 10/12); difficulty driving ( N  = 9/12); impaired relationships with friends, family, and/or partner ( N  = 9/12); and reduced social participation ( N  = 9/12) (Fig.  3 b). Example patient quotes for the most frequently reported HRQoL impacts across each domain and for each impact are provided in Table  3 and Supplementary Table S3, respectively. Clinicians reported at least one HRQoL impact across all except one of the domains (financial); however, patients reported more HRQoL impacts than clinicians (50 vs. 16; Fig.  4 ).

a Impact of MOGAD on HRQoL reported at the domain level by patients and clinicians. b  HRQoL impact concepts reported by patients. HRQoL, health-related quality of life; MOGAD, myelin oligodendrocyte glycoprotein antibody-associated disease

Table 3 Overview of the most commonly reported HRQoL impacts across each impact domain with example quotes from patient interviews HRQoL impact domain/concept No. of patients a Example quotes from patient interviews Emotional wellbeing  Depression 10/12 “I do think when you're constantly not feeling well and you're…constantly in pain, constantly tired…how do you stay positive through all that?…I would say I have experienced depression…my mood has been very negatively affected” Activities of daily living  Difficulty carrying out household chores 11/12 “Standing washing the dishes is very difficult some days…I have a basement. That's where my washer and dryer are…some days using the steps to go up and down is harder than other days” Physical functioning  Difficulty walking 10/12 “As of right now I had a transverse myelitis attack in June 2021 and I’ve been on a cane and/or walker since. I’m finally seeing some…improvement in my mobility and I’m trying to capitalize on that as much as possible” Social functioning  Impaired relationships with friends/family and/or partner 9/12 “If I’m…having bad days, it’s hard to keep up with some of my friends…they want to talk to you every day…sometimes I have days where I don’t want to talk to anybody…I’m having brain fog. I’m having a migraine. Don’t talk to me. Leave me alone”  Reduced social participation 9/12 “Because of all the symptoms, I really didn’t have energy for anything outside of work…since the transverse myelitis attack, I've been very isolated…when you get severely sick to the point where you're not able to reciprocate it…people tend to fall out of the woodwork in my experience. I've definitely become very isolated” Work/school  Inability to work 11/11 “You know, I've lost my vision, kind of dropping everything, not being able to go to work…just to go and get those relapses under control” Cognitive functioning  Difficulty concentrating 8/11 “Well it’s very difficult to concentrate whenever your head is throbbing…it was also hard to keep a conversation…I couldn’t concentrate to save my life” Sleep  Insomnia 4/10 “Then the eye pains, my god. It was so bad that I couldn’t even sleep at night”  Nighttime awakenings 4/10 “When I for example have eye pain or a headache, I would probably not sleep or I would wake up around four times or during the night” Financial  Financial strain/burden (e.g., cost of treatment 7/7 “The only person that's working is my wife…it’s very difficult to pay rent, do grocery shopping, and stay up to date on my prescriptions…it's hard to have a job, so I don’t have [health] insurance” Patient IDs are not included to maintain anonymity and avoid potential identification of patients from their combination of symptoms, but quotes in this table represent statements from five different patients a All patients did not report each HRQoL domain (italics). The denominator represents the total number of patients that reported the respective HRQoL domain HRQoL, health-related quality of life; MOG, myelin oligodendrocyte glycoprotein; MOGAD, myelin oligodendrocyte glycoprotein antibody-associated disease

Overview of the most commonly reported HRQoL impacts across each impact domain with example quotes from patient interviews

Patient IDs are not included to maintain anonymity and avoid potential identification of patients from their combination of symptoms, but quotes in this table represent statements from five different patients

a All patients did not report each HRQoL domain (italics). The denominator represents the total number of patients that reported the respective HRQoL domain

HRQoL, health-related quality of life; MOG, myelin oligodendrocyte glycoprotein; MOGAD, myelin oligodendrocyte glycoprotein antibody-associated disease

Final conceptual model for the patient experience of MOGAD as determined by patient/clinician interviews, published literature, and patient blogs. a A clinician reported that fever is a precursor to a MOGAD attack rather than a symptom of MOGAD. b Currently, there are no treatments approved for use in MOGAD by any health authority. HRQoL, health-related quality of life; MOGAD, myelin oligodendrocyte glycoprotein antibody-associated disease

Patients reported that impacts on work/school were the most bothersome ( n  = 5/12) and the impacts they would most like to see improved ( n  = 4/12). One clinician reported that physical impacts are most bothersome for patients, particularly in association with vision loss.

Treatment

All patients reported that they were receiving, or had previously received, treatment for MOGAD symptoms. Patients reported 13 different types of treatment and three unspecified treatments (Supplementary Fig. S1 ). The most frequently reported treatments were corticosteroids ( N  = 10/12), immunoglobulin ( N  = 7/12), immunosuppressants ( N  = 3/12), and anti-epileptic medications ( N  = 3/12).

Conceptual Saturation

Conceptual saturation was achieved for 26/30 symptoms, with these symptoms emerging spontaneously in the first eight patient interviews. The four symptoms that did not achieve saturation (i.e., were not spontaneously mentioned prior to the final group of interviews) were fever, throat symptoms, difficulty breathing, and bowel symptoms, suggesting that these symptoms may be less proximal to the patient experience of MOGAD. Saturation was achieved for all HRQoL impact domains, with concepts relating to all domains emerging spontaneously in the first four patient interviews. Overall, the saturation analysis provides evidence that saturation was achieved and that the concepts have been thoroughly and sufficiently explored.

Final Conceptual Model

The final conceptual model includes 32 symptoms across seven domains and 50 HRQoL impacts across eight domains (Fig.  4 ). Compared to the preliminary model, some symptom and impact concepts have been classified at a broader level, and terminology has been refined to account for the number of symptom and impact concepts that emerged in the qualitative interviews. All symptom and impact concepts that were mentioned within the literature mapped onto those that emerged in the qualitative interviews.

Ten additional symptoms were identified in patient interviews, including loss of appetite, blurred vision, loss of color vision, sensory changes, dizziness, difficulty swallowing, neuropsychiatric symptoms, tremor, muscle spasms, and nausea. Two additional symptoms were identified in clinician interviews: light sensitivity and sexual dysfunction. All 12 newly emerged symptom concepts were added to the final conceptual model. Two additional HRQoL impact domains (cognitive functioning and financial impacts), as well as 37 new impact concepts across all domains, were added to the final conceptual model.

Discussion

To our knowledge, this is the first qualitative study to explore the patient experience of MOGAD. A conceptual model of MOGAD was developed to integrate insights from published literature and patient and clinician perspectives to incorporate the patient voice.

The final conceptual model captured 32 symptoms and 50 HRQoL impacts across multiple domains. Although the symptoms and impacts identified in the interviews were largely consistent with published retrospective studies, case reports, and literature reviews [ 32 – 35 ], several additional concepts were identified; as such, the study findings provided further qualitative depth than was previously available. Moreover, this conceptual model demonstrates the breadth and heterogeneity of MOGAD symptoms and impacts from the patient perspective and highlights the underappreciated burden of disease.

The small sample size means that frequency of individual symptoms should be interpreted with caution. Nevertheless, it is important to note that the most frequently reported symptoms were eye pain, fatigue, body aches/pain, blurred vision, and headaches, suggesting that these symptoms are core to the MOGAD patient experience.

Both clinicians reported eye pain as one of the most frequently experienced symptoms of MOGAD. The study findings are consistent with published literature; eye pain is common in patients with MOGAD, particularly in patients who present with ON [ 4 , 34 , 36 , 37 ]. An estimated 65–86% of patients experience MOGAD-related ON pain and pain on eye movement [ 34 ]. Similarly, headaches are estimated to affect 47–75% of patients [ 37 – 39 ]. Given that ON is the most common initial and relapse manifestation in adults [ 4 ], it is not surprising that eye pain and blurred vision were frequently reported in this study. However, only three patients reported experiencing ON, suggesting ON may have been under-represented or under-reported in the study sample.

Whilst acute and chronic symptoms were not differentiated in this study, some patients mentioned the duration of their symptoms. Symptoms including weakness, fatigue, body aches/pain, eye pain, loss of appetite, numbness/tingling, and urinary symptoms/difficulties were experienced as constant symptoms by some patients. This may provide preliminary insights into the chronicity of symptoms; however, further data would be needed to confirm this, given that symptom duration was not a primary focus of this study. This may also require the use of additional tools to assess patient quality of life, beyond those currently in common practice. Limited data on chronic MOGAD symptoms are available; however, a 51–86% prevalence of chronic MOGAD-related pain has been reported [ 33 , 40 ], and 54% of patients have reported frequent sleeping difficulties [ 41 ].

Although symptoms reported by patients and clinicians were generally concordant, clinicians reported light sensitivity and sexual dysfunction as symptoms of MOGAD while patients did not. Patients considered light sensitivity to be part of other symptoms, such as eye pain and headaches, rather than a standalone symptom. Erectile dysfunction has been reported in men with MOGAD, particularly in those presenting with TM at onset [ 13 , 36 ]. Given the sample size and proportion of women in the present study, it is possible that this symptom was not apparent in this patient sample; it is also possible that given the sensitivity of the topic, patients may not have felt comfortable disclosing it in their interview.

Eye pain and body aches/pain were reported by patients to be the most bothersome symptoms and the most important to improve with treatment. Similarly, interviewed clinicians considered pain as the most important symptom to improve with treatment. These findings provide insights that can be considered for the assessment of symptoms in clinical trials investigating treatments for MOGAD.

Literature on the HRQoL impacts of MOGAD is limited, but suggests that, similar to other neuroinflammatory diseases [ 42 , 43 ], MOGAD has a substantial impact on patients’ lives. Consistent with this, the most frequently reported HRQoL impacts by patients in this study were difficulties with household chores, inability to work, difficulty walking, and depression. Literature published on NMOSD, which has substantial symptom overlap with MOGAD, highlights the impact of disease on ADL and physical functioning [ 44 – 46 ]. Depression has also been previously reported in patients with MOGAD, with one study reporting that 31% of patients displayed evidence of depression [ 47 ] and another study reporting moderate or greater depression in 42% of patients, increasing to 60% in patients who experience MOGAD-related pain [ 33 ]. Consistent with inability to work being a frequently reported impact, patients with MOGAD report leaving employment at a rate of 14.5%, reducing weekly work hours by 38%, and 43% report losing wages post-MOGAD diagnosis [ 48 ]. A study reported that, of patients with MOGAD ( n  = 90) who were not in full-time employment, 62% were not in full-time employment due to reasons relating to MOGAD [ 49 ]. Additionally, a study in patients with NMOSD ( n  = 166) and MOGAD ( n  = 46) reported that 60% of patients were unemployed, and among those who work, many reduced their hours or take sick leave, which often affects salary [ 50 ]. In our study, patients considered the impact on work/school to be the most bothersome impact and most important to improve.

There was general concordance between impact domains reported by patients and clinicians, although as expected patients reported more detailed accounts of various impact concepts compared with clinicians.

Methodological limitations of this study include the small sample size (patients, n  = 12; clinicians, n  = 2), which reflects the qualitative nature of the study and the rarity of the disease. Study findings should be understood as highlighting some of the core experience for this rare disease rather than providing a complete clinical description of MOGAD; caution should be exercised when drawing conclusions based on the experiences of this limited sample. The findings from this study may not be fully generalizable across different countries and cultures, to pediatric or adolescent populations, or to populations of other ethnicities. Further, the experiences of patients with monophasic MOGAD were not captured, and there may be additional variability in patients’ experience of relapses, which was not explored. However, the sample size aligned with conceptual saturation principles [ 27 – 29 ], and conceptual saturation was achieved for the patient interviews, suggesting that the concepts have been thoroughly and sufficiently explored. Research with larger samples of patients, with representation across demographic and clinical characteristics, would be useful for investigating the generalizability of the conceptual model. Despite its limitations, our study provided considerable insight into the patient experience of MOGAD.

Conclusions

This study provides important insights into the experience of MOGAD from patient and clinician perspectives, addressing a gap in the literature and highlighting the underappreciated burden of the disease. The final conceptual model demonstrates the heterogeneity of the symptoms of MOGAD and the impact on patients’ HRQoL. The additional in-depth insights from the qualitative interviews help to improve understanding of the patient experience of MOGAD. Additionally, this study highlights the symptoms and HRQoL impacts proximal to the patient experience; incorporating measures that assess these is an important consideration for future treatment trials to ensure that they are addressed.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 267 KB)

Acknowledgements

The authors thank the patients and clinicians who took part in this research. The authors also recognize Valerie Ciaravino, Natasha Rubenstien, Rebecca Williams-Hall, and Anjali Batish for their contributions to the research. The authors thank Margarita Lens, MSci, CMPP, of UCB for publication and editorial support.

Medical Writing Assistance

Medical writing support was provided by Niall Harrison, MSc, CMPP, and Reece Bracewell, MBiolSci, of Mimas, OPEN Health Communications, and Melanie Francis, a contract writer working on behalf of OPEN Health Communications, and was funded by UCB in accordance with Good Publication Practice (GPP) guidelines ( http://www.ismpp.org/gpp-2022 ) .

Author contributions

Conceptualization: N/A; data curation: Charlotte Cox, Megan Mayhew, Julia Stein; formal analysis: Charlotte Cox, Megan Mayhew, Julia Stein, Béatrice Tugaut; funding acquisition: N/A; investigation: Charlotte Cox, Megan Mayhew, Julia Stein; methodology: Asha Paireddy, Charlotte Cox, Megan Mayhew, Julia Stein, Teresa Gasalla; project administration: N/A; resources: Charlotte Cox, Megan Mayhew, Julia Stein; software: N/A; supervision: Julia Stein, Béatrice Tugaut; validation: N/A; visualization: Charlotte Cox, Megan Mayhew, Julia Stein, Béatrice Tugaut; writing – original draft: Jeffrey L. Bennett, Asha Paireddy, Charlotte Cox, Megan Mayhew, Julia Stein, Teresa Gasalla, Béatrice Tugaut; writing – review and editing: Jeffrey L. Bennett, Asha Paireddy, Charlotte Cox, Megan Mayhew, Julia Stein, Teresa Gasalla, Béatrice Tugaut.

Funding

This study, conducted by Adelphi Values, and the journal’s Rapid Service Fee were funded by UCB. The funders were involved in study methodology, analyses, and decision to publish the results.

Data availability

Data from non-interventional studies are outside of UCB’s data-sharing policy and unavailable for sharing.

Declarations

Conflicts of Interest

Jeffrey L. Bennett has served as a Consultant for Horizon Therapeutics, Genentech, TG Therapeutics, Reistone Bio, Roche, Antigenomycs, Chugai, Mitsubishi Tanabe, EMD Serono, Beigene, Novartis, and ImCyse. He has served on scientific advisory and Data Safety Monitoring boards for Clene Nanomedicine and Roche. He serves on a Speakers Bureau for Alexion and received research support from Novartis and Alexion. Asha Paireddy is an employee of UCB. Charlotte Cox is an employee of Adelphi Values, a health outcomes agency that was commissioned by UCB to conduct the research. Megan Mayhew is an employee of Adelphi Values, a health outcomes agency that was commissioned by UCB to conduct the research. Julia Stein is an employee of Adelphi Values, a health outcomes agency that was commissioned by UCB to conduct the research. Teresa Gasalla is an employee of UCB. Béatrice Tugaut is an employee and shareholder of UCB.

Ethical Approval

This study was conducted in accordance with the Declaration of Helsinki, International Conference on Harmonization guidelines for Good Clinical Practice, and other current data-protection guidance. Ethical approval was provided by Western Copernicus Group Independent Review Board (IRB #20222224; valid from December 19, 2022 to May 2, 2023). Written informed consent was obtained from each patient and clinician prior to study participation.

Footnotes

Prior presentation: The results from this manuscript have been in part previously presented at the 40th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), 18–20 September 2024, Copenhagen, Denmark, and at the 42nd annual meeting of the Japanese Society of Neurological Therapeutics (JSNT), 7–9 November 2024, Tokyo, Japan.

References

Associated Data

Supplementary Materials

Supplementary file1 (PDF 267 KB)

Data Availability Statement

Data from non-interventional studies are outside of UCB’s data-sharing policy and unavailable for sharing.