Overall, 74 neurologists participated in the physician survey, of which 53/74 were in EU5 (71.6%) and 21/74 in the US (28.4%). Neurologists reported caring for a median of 4.0 (Q1, Q3: 2.0; 6.0) patients with MOGAD in a typical month. Around half of neurologists had clinical trials experience in MOGAD at the time of the survey (currently involved: 5.4%, have been, but not currently involved: 47.3%, Table 1).

Neurologists completed PRFs for 268 patients with MOGAD, of which 213/268 were in EU5 (79.5%) and 55/268 in the US (20.5%). Overall, the median patient age at survey completion was 36.0 years (Q1, Q3: 28.0; 43.0 years), with a marginally younger population in EU5 compared to the US [median patient age 35.0 (Q1, Q3: 27.0; 43.0) and 38.0 (Q1, Q3: 35.0; 43.0), respectively]. In total, 173/268 (64.6%) of patients were female. Overall, most [229/268 (85.4%)] surveyed patients were White/Caucasian, with 195/213 (91.5%) in the EU5 sample and 34/55 (61.8%) in the US sample. Most of the patients, 171/268 (63.8%) did not have a physician-reported comorbidity as separate from their MOGAD diagnosis; among those who did have a comorbidity, the most prevalent was depression [39/97 (40.2%)]. The sample of patients included a higher proportion of monophasic patients [i.e., those who had not yet experienced a relapse at the time of data collection, 178/268 (66.4%)] than relapsing patients [90/268 (33.6%)] with similar characteristics (Table 2, Table S1).

In total, 66 patients (patient response rate: overall, 24.6%; EU5, 27.7%; US, 12.7%) completed PSCs, with no PSCs completed for the UK and Italy. Of the patients that completed the PSC questionnaire, 36/66 (54.5%) had a monophasic course and 30/66 (45.4%) had relapsing disease (Table S2).

The overall median age of patients at symptom onset was 32.5 years (Q1, Q3: 24.6; 39.7) and the median age at definitive diagnosis (positive serum MOG antibody test) was 33.3 years (Q1, Q3: 25.6; 40.1). Between regions, median age at symptom onset and at definitive diagnosis were greater in the US sample [36.8 (Q1, Q3: 31.8; 40.7) median years, and 37.4 (Q1, Q3: 31.8; 42.4) median years, respectively] than in the EU5 sample [30.9 (Q1, Q3: 23.7; 39.6) median years, and 31.7 (Q1, Q3: 24.0; 39.7) median years, respectively] (Table 2).

Prior to receiving a definitive MOGAD diagnosis, 64.2% of patients (172/268) were given preliminary or alternative diagnoses. Among patients who received a preliminary or alternative diagnoses, the three most frequent were optic neuritis [72/172 (41.9%)] multiple sclerosis [47/172 (27.3%)] and transverse myelitis [44/172 (25.6%)] (Fig. 2).

At the point of data collection, patients had been diagnosed with MOGAD a median (Q1, Q3) of 18.5 (8.3, 35.4) months. In EU5 this was a median (Q1, Q3) 19.3 (9.7, 40.0) months and in the US this was 16.2 (7.9, 25.9) months. When stratified by disease course, this was a median (IQR) 24.1 (14.7, 51.4) months in relapsing patients and 16.0 (6.7, 29.4) months in monophasic patients. Of those who received a preliminary or alternative diagnosis prior to definitive MOGAD diagnosis (n = 172/64.2%), the overall median (Q1, Q3) of physician-reported time from symptom onset to alternative diagnosis was 19.0 (0.0; 59.0) days, while the median (Q1, Q3) time from symptom onset to definitive diagnosis of MOGAD was 67.0 (31.0; 151.0) days. The overall median (Q1, Q3) time from alternative diagnosis to definitive diagnosis was 31.0 (16.0; 89.0) days (Fig. 1a). When looking at the frequency distribution of time from symptom onset to definitive diagnosis, 12% of patients had a diagnostic journey of 1 year or more (Fig. 1b). Among patients who received preliminary/alternative diagnoses, 96% (165/172) received acute treatment during their first symptomatic episode, compared with 84% (81/96) who didn’t receive a preliminary/alternative diagnosis (Fig. 2).

a Time from symptom onset to alternative diagnosis and MOGAD definitive diagnosis, among MOGAD diagnosed patients who received an alternative diagnosis prior to MOGAD (n = 172), informed by participating neurologists. Abbreviations: Q1, Q3, interquartile range; MOGAD, myelin-oligodendrocyte glycoprotein antibody-associated disease; n, number of PRF responses; PRF, patient record form. The dates of symptom onset, alternative diagnosis and MOGAD diagnosis were recorded separately in the PRF, and unknown was allowed as a response in each case; therefore, the final number of patients included in each time point measurement could differ. b Distribution of time from symptom onset to alternative diagnosis and MOGAD diagnosis among patients with an alternative diagnosis (n = 139)

Alternative diagnoses before definitive MOGAD diagnosis, among MOGAD diagnosed patients who received an alternative diagnosis prior to MOGAD (n = 172), informed by participating neurologists. Abbreviations: ADEM, acute disseminated encephalomyelitis; AQP-4 NMOSD, aquaporin-4 neuromyelitis optica spectrum disorder; MOGAD, myelin-oligodendrocyte glycoprotein antibody-associated disease; n, number of PRF responses; PRF, patient record form. *Categories are not mutually exclusive

Overall, 50.8% of patients first consulted with a neurologist about their MOGAD symptoms, either the neurologist currently responsible for the patient’s care (91/268, 34.0%) or another neurologist (45/268, 16.8%). Signs prompting MOGAD antibody testing, where known, were most commonly negative serology for AQP-4 antibodies [165/268 (61.6%)], detection of longitudinally extensive myelitis [126/268 (47.0%)] and bilateral optic neuritis [116/268 (43.3%)]. The presence of extensive T2 and gadolinium (Gd)-enhancing lesion of the optic nerve or chiasm [60/268 (22.4%)], and perineural Gd-enhancement of the optic nerve upon MRI [53/268 (19.8%)], also prompted MOG antibody testing in ≥ 20% of patients in the overall sample. In 220/268 (82.1%) of cases, it was the neurologist currently responsible for the patient’s care who provided the patient with their diagnosis of MOGAD (Table 3).

To confirm MOGAD diagnosis, patients underwent a median 12.0 [Q1, Q3: 9.0; 19.0] assessments, tests and/or scans (see Table S3 for full list). The median number of assessments was 14.0 (Q1, Q3: 9.0; 20.0) in the EU5 sample and 9.0 (Q1, Q3: 5.0; 12.0) in the US sample. MOG antibody detection (cell-based assay) was used in all patients across regions to aid MOGAD diagnosis. Other frequently used tests (> 80% of all patients) included brain MRI (90.3%), spinal MRI (87.3%), and protein electrophoresis (81.7%). Additional assessments used to diagnose MOGAD in > 50% of all patients included physical examination (72.0%), complete blood count (62.7%), visual evoked potential (60.4%), visual field test (57.8%), visual acuity test (56.0%) and white cell count in the CSF (54.1%) Although the frequency of use for each test was generally lower in the US sample than in the EU5 sample, test ranking remained largely consistent across regions (Table S2).

Initial optic, myelitic, and/or meningeal/encephalitic presenting symptoms were present in substantial proportions of patients [182/268 (67.9%), 175/268 (65.3%) and 152/268 (56.7%) of patients, respectively]. The most common sign/symptoms across all categories were decreased visual acuity and muscle weakness, present in 139/268 (51.9%) and 120/268 (44.8%) of patients overall, respectively. Other signs/symptoms present in > 20% of patients included eye movement pain (35.4%), paraesthesia (28.4%), decreased visual field (26.2%), fatigue (25.7%), paraparesis (22.8%), and headache (21.6%) (Fig. 3).

Initial presenting signs and symptoms among patients with MOGAD grouped by symptom category, informed by participating neurologists

The severity of initial presenting symptoms was wide ranging but generally moderate (Figure S1). Potentially disabling or serious signs were present in a limited number of patients with a prevalence < 10%. (i.e., cranial nerve palsy, unilateral blindness or bilateral blindness, seizures, respiratory failure, and coma).

Overall, relapses were reported in 90/268 (33.6%) of patients. In patients with relapses, 77.8% of patients (70/90) were reported to have had only one relapse between the first symptomatic episode and survey completion. The median time from initial symptomatic episode to first relapse was 17.0 (Q1, Q3: 4.9; 29.0) months. Among patients with a relapse, symptoms were similarly distributed between optic, myelitic and meningeal/encephalitic symptoms (Table 4).

In total, 246/268 patients (91.8%) received treatment for an acute attack (i.e., provided to a patient at the first MOGAD attack). At the point of data collection, 79/246 (32%) of patients who received acute treatment were relapsing patients, compared to 167/246 (68%) of monophasic patients, with similar results also seen for patients receiving maintenance treatment [relapsing patients: 81/223 (36%) vs monophasic patients: 142/223 (64%)]. Of treatments received, the most frequently used was IV methylprednisolone, used in 203/268 (75.7%) of patients; more frequently among monophasic patients. Other treatments received by > 5% of patients included oral prednisolone/prednisone (7.1%), PLEX (6.0%), IV prednisolone (5.6%) and IVIg (5.2%) (Fig. 4a).

a Acute treatment received reported during the initial symptomatic episode among patients with MOGAD, informed by participating neurologists. b Maintenance treatment received after the initial symptomatic episode among patients with MOsGAD, informed by participating neurologists. Abbreviations: EU5, France, Germany, Italy, Spain, and United Kingdom; IV, intravenous; IVIg, IV immunoglobulins; MOGAD, MOGAD, myelin-oligodendrocyte glycoprotein antibody-associated disease; n, number of PRF responses; PLEX, plasma exchange; PRF, patient record form; RTX, rituximab

No maintenance treatment (long-term therapy aimed at preventing further MOGAD episodes) was prescribed to 44/267 (16.5%) of patients. The most common reasons given for this were that the patient refused medication [24/44 (54.6%)], that the patient was considered to have a very low risk of relapse [10/44 (22.7%)] and/or other not specified reason [8/44 (18.2%)] (data not shown). Maintenance treatment was received by 81/90 (90.0%) of relapsing patients compared to 142/177 (80.2%) of monophasic patients. Among patients who received maintenance treatment [223/267 (83.5%)], the most commonly received treatments were oral prednisolone/prednisone [75/267 (28.1%)] and rituximab [75/267 (28.1%)]. Other maintenance treatments received by < 20% of the patients included azathioprine (16.1%) mycophenolate (9.4%), IVIg (6.4%) and PLEX (2.6%) (Fig. 4b).

Hospitalisations over the last 12 months before survey completion were reported in 78/268 (29.1%) of patients overall. The median number of nights spent in hospital was 7.0 (Q1, Q3: 5.0; 9.0). The primary reason given for hospital admission was to receive plasmapheresis or infusion of treatment [38/78 (48.7%) of patients]. MOGAD relapses and complications were reasons for admission in 10/78 (12.8%) and 6/78 [7.7%] of patients, respectively. Where known, 48.7% of admissions (38/78) were not through the emergency room (ER), and 92.3% of patients (72/78) did not visit the intensive care unit (ICU) (Table 5).

Neurologist-reported overall patient quality of life was most-frequently described as ‘very good’, ‘good’ or somewhat good’ [171/268 (63.8%) patients]. The extents to which MOGAD limited physical functioning, social functioning, and emotional wellbeing was most frequently described by neurologists as ‘a little’ [100/268 (37.3%), 94/268 (35.1%) and 92/268 (34.3%), respectively], followed by ‘a moderate amount’ [77/268 (28.7%), 68/268 (25.4%) and 67/268 (25.0%), respectively] (Table 6). As reported via the SF-36 questionnaire, patients most frequently self-reported that physical health/emotional problems interfered with normal social activities ‘not at all’ [26/66 (39.4%)] or ‘moderately’ [19/66 (28.8%)].

With respect to employment, 40.7% of patients were reported by physicians to be in full-time employment (109/268). Of those patients that were not in full-time employment (part-time work/on long-term sick leave/unemployed/retired due to MOGAD), 66.7% of these patients self-reported that this was due to reasons relating to MOGAD [monophasic patients (34/51 [66.7%]), relapsing patients (22/39 [56.4%]), with more missing responses among the relapsing patients]. In responses to the WPAI questionnaire, patients self-reported that the median of overall self-reported percentage of impairment while working, overall work impairment, and activity impairment due to MOGAD were 30.0% (Q1, Q3: 10.0%; 50.0%), 30.0% (Q1, Q3: 17.5%; 50.0%) and 30.0% (Q1, Q3: 10.0%; 50.0%), respectively (Table 7).