To Örebro University

BACKGROUND: Multiple sclerosis (MS) is a progressive disease that may affect respiratory muscle function. Pulmonary dysfunction may be subclinical, and posture changes can reduce lung volumes, especially in the presence of respiratory muscle weakness.

OBJECTIVE: To determine whether lung function differs between sitting and supine positions in individuals with moderate MS, and to explore associations with respiratory muscle strength and disability.

METHODS: Forty-eight participants with moderate MS (13 men, 35 women; median Expanded Disability Status Scale (EDSS) 4.5, range: 4.0-6.5) underwent spirometry (VC, FVC, FEV1, PEF) in sitting and supine positions. Respiratory muscle strength was assessed using maximal inspiratory (MIP) and expiratory pressures (MEP).

RESULTS: VC and FVC did not differ significantly between positions. FEV1 and PEF were slightly reduced in the supine position (p ≤ 0.001), with median relative decreases of -6% and -10%, respectively. These changes did not correlate with EDSS, MIP, or MEP. No sex-related differences were observed.

CONCLUSION: FEV1 and PEF are reduced in the supine position in individuals with moderate MS, indicating early positional respiratory changes. These alterations appear independent of disability level or respiratory muscle strength. However, it remains uncertain whether these changes differ from those of healthy individuals. Controlled studies are warranted to clarify their clinical significance.

BACKGROUND: Rituximab, a B-cell-depleting therapy widely used for multiple sclerosis (MS), is associated with a progressive decline in immunoglobulin G (IgG) levels, raising concerns regarding infection risk. This study evaluates IgG dynamics and antibiotic use in a real-world MS cohort.

METHODS: A retrospective cohort study was conducted on MS patients treated with Rituximab over a 10-year period. Patients included had at least two infusions and a follow-up of ≥6 months after the last infusion. IgG levels and antibiotic prescriptions were registered longitudinally.

RESULTS: The study included 213 patients (72% female, mean age 40.1 ± 10.6 years). Mean IgG decreased from 11.5 ± 2.4 g/L at baseline to 9.0 ± 1.7 g/L after five years, with an average decline of 0.35 g/L/year (95% CI 0.25-0.44; p < 0.001). Hypogammaglobulinemia (<6.7 g/L) occurred in 7.5% of patients. Cumulative rituximab dose was a significant predictor of lower IgG (p < 0.001). Antibiotic prescriptions were recorded in 62% of patients (mean 2.5 per patient), most commonly for urinary (29%) and respiratory (17%) tract infections. In multivariable analysis, lower IgG levels did not significantly predict the risk of antibiotic prescription.

CONCLUSION: Rituximab treatment resulted in a significant, dose-dependent IgG decline. However, this decline was not associated with an increased risk of antibiotic-treated infections, suggesting a dissociation between total IgG levels and functional immune competence in this cohort. These findings support continued use of rituximab with vigilant monitoring, though dose adjustments may be warranted for patients with rapidly decreasing IgG.

Introduction: Cladribine is a deoxyadenosine analogue prodrug that induces immune reconstitution by selectively targeting B- and T-lymphocytes. Cladribine tablets (CladT) are administered in two courses, 12 months apart, for persons with MS (PwMS) with relapsing multiple sclerosis (RMS). Post-marketing surveillance is important for evaluation of long-term safety and effectiveness in a real-world setting. CLADCOMS (CLADribine tablets long-term Control Of MS) is a post-marketing investigator driven study.

Objectives/Aims: To investigate the proportion of PwMS free from disease activity with a CladT treatment duration of at least 36 months.

Methods: CLADCOMS includes patients with RMS from eight academic neurology clinics in Sweden who started CladT treatment after 23rd of March 2018. Data are prospectively registered in the Swedish Neuroregistry using highly structured annual follow-ups. Descriptive data, relapses, MRI activity, and B-cell lymphocytes levels were obtained from the registry. All statistics were performed using Wilcoxon Signed Rank Test.

Results: By March 2025, a total of 147 patients had a treatment duration with CladT of 36 months. The majority of PwMS in this cohort were treatment-naïve (33%) prior to CladT initiation, or had been treated with natalizumab (19%), anti-CD20 (16%) or dimethyl fumarate (12%).

The proportion of PwMS being relapse-free over 36 months was 78.2 %, compared to 61.8%, in the year prior CladT start (p= 0.013). For previously treatment-naïve PwMS, 68.7% were relapse-free, compared to 31.2% in the year prior to CladT start (p=0.012). The proportion with new T2 lesions on annual imaging significantly decreased from 11% during the first 12 months to 3% (p<0.01) during year 3. More results will be included in the final presentation.

Analys of total B-cell lymphocyte counts showed a drop from baseline (0.42x109/L cells ±0.80) to year 1 (0.20 x109/L cells ±0.18),(p<0.005). The proportion of CD19+/CD27+ B-cells dropped from 12% ± 9% at baseline to 3% ± 3% after 12 months (p<0.005) and the proportions of CD19+ B-cells increased from 68.0% ±13.5% at baseline to 83.0% ±8.7 after 12 months (p<0.005).

Conclusion: CladT treatment showed clinical stability after 36 months regardless of previous treatment. The unique immune modulation helps to explain the durability of the effect of CladT. However, continued follow-up is needed to assess the effectiveness and safety of treatment with CladT to investigate time to disease re-activation after full treatment.

Introduction: Cladribine is a deoxyadenosine analogue prodrug targeting proliferating B- and T-lymphocytes. Cladribine tablets (CladT) are administered in two courses, 12 months apart, for persons with MS (PwMS) with relapsing MS (RMS). Some PwMS may receive one or more further doses at the discretion of their neurologist.

CladT is included in the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology 10” (IMSE 10).

Objectives/Aims: To assess the safety and effectiveness of CladT with focus on PwMS treated with CladT with at least 3 years of follow up.

Methods: Data on Extended Disability Status Scale (EDSS), MS Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), MS Impact Scale (MSIS-29), European Quality of Life -5 Dimensions Test (EQ-5D), Visual Analog Scale (VAS) scores, relapses, lesions and Adverse Events (AEs) were collected from the nationwide Swedish Neuro Registry (NeuroReg). Effectiveness measures and changes in relapse rates were assessed using Wilcoxon Signed Rank Test.

Results: A total of 459 CladT exposed (PwMS) have been included in IMSE 10 since the launch of CladT in April 2018 of which 90% remained with CladT while 47 patients (10%) discontinued treatment at any time after initiation. The most common reason for discontinuation was lack of effect (75%). All AEs reported to the Swedish Medical Products Agency will be shown.

A total of 194 (42%) had CladT exposure for ⩾36 months of which 23% were treatment naïve prior to CladT initiation. 19% switched from natalizumab, 10% from dimethyl fumarate and 10% from anti-CD20 to CladT treatment. In this cohort 93% did not switch to another treatment during the following 36 months since treatment initiation with CladT.

The 36-months cohort demonstrated clinical stability with a numerical trend for improvement in mean MSSS, SDMT, MSIS-29 Psychological/Physical scores compared with baseline. All other outcomes remained stable. The mean annual relapse rate (ARR) decreased significantly (p<0.05) during all treatment years compared to the ARR in the year prior to treatment start (0.32±0.60 to 0.06±0.26 year1, 0.04±0.22 year2, 0.01±0.07 year 3). The number of PwMS with new T2 lesions decreased from 8% year 1 of CladT treatment to 2% year 2 and 3% year 3.

Conclusion: Most PwMS exposed for ⩾36 months to CladT display clinical stability and significant improvements in ARR and T2 lesions. Longer observation times will be needed to assess the effectiveness and safety of CladT beyond 36-month exposure.

Introduction: Ofatumumab is a human CD20 monoclonal antibody targeting B-cells and a small population of CD20+ T-cells. The treatment is administered once a month (after initial dosing) with subcutaneous injections for persons with MS (PwMS) with relapsing MS (RMS). Ofatumumab is included in the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology 12” (IMSE 12).

Objectives/Aims: To assess effectiveness and safety of ofatumumab with focus on 12 months treatment outcomes.

Methods: Data on Extended Disability Status Scale (EDSS), MS Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), MS Impact Scale (MSIS-29), relapses and Adverse Events (AEs) were collected from the nationwide Swedish Neuro Registry (NeuroReg). Effectiveness measures and relapse rates were assessed using Wilcoxon Signed Rank Test. All reported AEs were collected from the Swedish Medical Products Agency (MPA).

Results: 188 ofatumumab treated PwMS have been included in IMSE 12 since March 2021. 38% of PwMS had switched from rituximab (age 38.9 ± 10.4, duration (months) since diagnosis (DSD) 107.2 ± 74.5), 25% from natalizumab (age 40.6 ± 10.3, DSD 77.6 ± 76.6), 12% had been treatment naïve/no treatment registered prior start with ofatumumab (age 45.2 ± 12.0, DSD 2.6 ± 4.5) and 25% from other treatments (age 42.2 ± 10.6, DSD 129.2 ± 77.3).

15 PwMS discontinued treatment due to AEs (n=9; 5 unspecified, 2 headaches and 2 infections), other reasons (n=4) and pregnancy (n=2). 9 AEs were reported to the MPA (7 serious, 2 non-serious) from 4 individuals.

107 PwMS have been treated with ofatumumab for ⩾12 months. The ⩾12month cohort demonstrated a non-significant trend for improvement in mean EDSS, MSSS and SDMT score compared with baseline (EDSS; 2.6 ± 2.5 to 2.5 ± 2.6, p=0.478, MSSS; 3.7 ± 3.1 to 3.5 ± 3.0, p=0.394 SDMT; 55.7 ± 11.5 to 56.0 ± 11.1, p=0.491). The mean annual relapse rate (ARR) decreased significantly (p=0.005) during first year of treatment (0.03 ± 0.22) compared to the ARR (0.10 ± 0.30) one-year prior treatment initiation. The number of PwMS with new T2 lesions decreased significantly (p=0.04) from 6 PwMS the first treatment year with new T2 lesions to none the second treatment year.

Conclusion: PwMS treated for ⩾12 months display clinical stability. Significant improvements were seen in both ARR and the proportion of patients with new T2 lesions. Longer observation times will be needed to assess the effectiveness and identify potential AEs of ofatumumab.

Introduction: Cladribine is a deoxyadenosine analogue prodrug targeting proliferating B- and T-lymphocytes. Cladribine tablets (CladT) are administered in two courses, 12 months apart, for Persons with MS (PwMS) diagnosed with remitting multiple sclerosis (RMS). CladT is included in the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology substudy 10” (IMSE 10).

Objectives/Aims: To assess effectiveness of CladT with focus on age at treatment start.

Methods: Two subgroups in the IMSE 10 study was compared, below <50 or above ⩾ 50 years of age at treatment start. Data on Extended Disability Status Scale (EDSS), MRI activity and annual relapse rate were collected from the nationwide Swedish Neuro Registry (NeuroReg). Effectiveness measures and relapse rates were assessed using Wilcoxon Signed Rank Test.

Results: By March 2025, a total of 459 CladT exposed PwMS have been included in IMSE 10 since the launch of CladT in April 2018. This cohort was divided into two subgroups, Below <50 (n=372) and Above ⩾50 (n=87) years of age at treatment start.

The proportion of PwMS that discontinued their treatments was five times higher in the younger subgroup (13%) compared to the older subgroup (2.3%) and the most common reason was “Lack of effect” (75.5%). The only given reason for the older subgroup was “other reasons” (100%).

The younger subgroup had a mean EDSS that was stable at 1.5 during the first and third treatment year. While the older subgroup showed a decrease in mean EDSS from 3.1 at baseline to 2.8. The mean annual relapse rate (ARR) decreased significantly the third year (mean± SE 0.01 ± 0.01, p<0.005, mean± SE 0.00 ± 0.00, p<0.05) compared to the ARR one-year prior CladT start (mean± SE 0.21 ± 0.03, mean± SE 0.17 ± 0.05) for the younger and older subgroups, respectively.

During the first year of treatment 9% of PwMS in the younger subgroup and 10% of PwMS in the older subgroup had new T2 lesions. During the second and third treatment year both subgroups had a decrease in MRI activity to 4% (year2, p=0.0005, year3, p=0.0009) in the younger subgroup and 0% (year 2, p=0.03, year3, p=0.07) in the older subgroup.

Conclusion: This data shows that PwMS below and above 50 years of age at treatment start exposed to CladT display clinical stability and a tendency for improvement compared with baseline in several of the investigated outcome measures. PwMS above 50 years at CladT start showed a tendency for less MRI activity compared to PwMS below 50 years of age at treatment start.

Introduction: Cladribine is a deoxyadenosine analogue prodrug that induces immune reconstitution by selectively targeting B- and T-lymphocytes. Cladribine tablets (CladT) are administered in two courses, 12 months apart, for persons with MS (PwMS) with relapsing multiple sclerosis (RMS). Post-marketing surveillance is important for evaluation of long-term safety and effectiveness in a real-world setting. CLADCOMS (CLADribine tablets long-term Control Of MS) is a post-marketing investigator driven study.

Objectives/Aims: To assess effectiveness of CladT at 36 months follow up with the focus on the number of treatments prior to CladT initiation.

Methods: CLADCOMS includes patients with RMS from eight academic neurology clinics in Sweden who started CladT treatment after 23rd of March 2018. PwMS being treatment naïve or exposed to one DMT prior to CladT were compared to PwMS exposed to two or more DMTs prior to CladT start. Data are prospectively registered in the Swedish Neuroregistry using highly structured annual follow-ups. Descriptive data, relapses and MRI activity were obtained from the registry. All statistics were performed using Wilcoxon Signed Rank Test.

Results: By March 2025, a total of 147 PwMS had a treatment duration with CladT of at least 36 months. In this cohort 74 PwMS had 0-1 DMTs (“low” subgroup) prior to CladT initiation and, 73 PwMS had 2 or more DMTs (“high” subgroup) prior to CladT. In the “low” subgroup, 66% were treatment-naïve and 11% had been exposed to natalizumab. In the “high” subgroup, the mean number of prior treatments was 4 which included anti-CD20 (29%) and natalizumab (29%).

The proportion of PwMS being relapse-free in the group with 0-1 DMT prior was 70% over 36 months of treatment compared to 36% the year before CladT initiation (p=0.005). The proportion of PwMS with new T2 lesions significantly (p=0.05) decreased from 11% during the first treatment year to 5% during the third year.

In the group with ⩾2 DMTs prior CladT, there was no significant difference in the proportion of PwMS being free of relapses in the year prior to treatment start (81%) and third treatment year (84%). There was a non-significant decrease in MRI lesion activity during the first treatment year (7%) and third treatment year (2%).

Conclusion: CladT treatment showed an improvement in clinical effectiveness after 36 months in the subgroup of PwMS with 0-1 prior treatments, where both relapse activity and MRI lesion activity decreased significantly. For the group with ⩾2 DMTs prior CladT the signs of residual inflammatory disease activity remained stable during the entire treatment period.

Introduction: Cladribine is a deoxyadenosine analogue prodrug targeting proliferating B- and T-lymphocytes. Cladribine tablets (CladT) are administered in two courses, 12 months apart, for persons with MS (PwMS) with relapsing MS (RMS). AntiCD20 (aCD20) and Natalizumab (NTZ) are the two most used MS drugs in Sweden. The effects of switching from these drugs to CladT needs further investigations to understand the impact on the clinical effectiveness of such a switch.

CladT is included in the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology 10” (IMSE 10).

Objectives/Aims: To assess the effectiveness of CladT with focus on PwMS treated with NTZ or aCD20 prior to CladT.

Methods: The cohort was divided into 3 groups based on treatment prior to CladT; NTZ, aCD20 and other. Data on Extended Disability Status Scale (EDSS), relapses and lesions were collected from the Swedish Neuro Registry. Wilcoxon Signed Rank Test and the McNemar’s statistical tests were used.

Results: A total of 459 CladT exposed PwMS have been included in IMSE 10. 82 PwMS were treated with NTZ prior to CladT and 87 with aCD20. The remaining 290 PwMS defined as other included 142 treatment naïve, 48 with dimethyl fumarate and 23 with missing data on prior treatment.

Mean EDSS values did not change significantly for the three groups over the 3-year follow-up period.

The ARR decreased significantly from 1 year prior to TS compared to the first and third year with CladT for all three groups (NTZ: 0.26 to 0.03 (yr1)/0.03(yr2)/0(yr3), aCD20: 0.16 to 0.05(yr1)/0.08(yr3), other: 0.38 to 0.08(yr1)/0.03(yr2)/0.01(yr3)). However, the aCD20 group had a significantly lower ARR the year prior to TS than the other two groups resulting in a non-significant decrease during the second follow-up year. The remaining two groups had significant decreases in ARR all three years.

The proportion of PwMS with new T2 lesions during CladT treatment dropped from 12% the first treatment year to 3% the following two years. This decrease was greater for PwMS previously treated with NTZ or other than aCD20. However, none of these differences were significant.

Conclusion: CladT was generally effective for the cohort as a whole. When the cohort was divided by previous treatment data showed greater improvements for PwMS previously treated with NTZ or other than aCD20. However, it is important to note that patients switching from aCD20 had a different profile with a higher initial EDSS level, lower ARR and fewer lesions than the remaining two groups.

Introduction: Rituximab, a B-cell-depleting therapy, is widely used for multiple sclerosis (MS). While effective, long-term treatment may reduce immunoglobulin G (IgG) levels, potentially increasing infection risk.

Objectives/Aims: This study evaluates IgG dynamics and antibiotic use in MS patients receiving Rituximab in Örebro County, Sweden.

Methods: A retrospective cohort study was conducted on MS patients treated with Rituximab over a 10-year period. Patients included had at least two infusions and a follow-up of ⩾6 months after the last infusion. IgG levels and antibiotic prescriptions were registered longitudinally.

Results: A total of 213 patients (72% female, mean age 40.1 ± 10.6 years) were included, with a mean follow-up time of 44.8 ± 10.6 months. The mean IgG level at treatment initiation was 11.5 ± 2.4 g/L, declining to 10.4 ± 2.3 g/L after the last infusion, with a mean decrease of 1.1 ± 1.4 g/L. Hypogammaglobulinemia (IgG < 6.7 g/L) occurred in 4% of patients. Serum IgG levels demonstrated a significant decline over the course of Rituximab treatment (p < 0.001). However, linear mixed modeling did not detect a statistically significant acceleration over time.

Antibiotic prescriptions were recorded in 63% of patients, with a mean of 2.5 ± 3.3 prescriptions per patient. The most common indications were urinary tract infections (29%) and respiratory tract infections (19%). No significant correlation was found between lower IgG levels and higher antibiotic use.

Conclusion: Rituximab treatment in MS was associated with a significant decline in IgG levels over time. However, the incidence of infections requiring antibiotics did not correlate with IgG decline, suggesting that most patients maintain sufficient immune function. These findings support the continued use of Rituximab in MS while highlighting the need for monitoring IgG levels during long-term treatment.

BACKGROUND AND OBJECTIVES: Myasthenia gravis (MG), an autoimmune disease characterized by fluctuating muscle weakness, is believed to result from complex gene-environment interactions, yet few risk factors have been identified. The objective of this study was to determine the effect of nicotine and alcohol on MG disease risk.

METHODS: The Genes and Environment in Myasthenia Gravis study is a Swedish, nationwide cross-sectional case-control study where prevalent patients with MG were invited to submit an extensive questionnaire on lifestyle and environment. Data collection took place between November 2018 and August 2019, and cases were matched by sex and year of birth to population controls. Year of disease onset was used as index year. Associations between use of alcohol, tobacco smoke, Swedish snuff, and MG risk were investigated using multivariable logistic regression.

RESULTS: A total of 1,067 patients with MG (mean age at onset 48 (SD 21) years, 53% female) were matched to 2,087 controls. Any alcohol consumption was associated with a lower MG risk compared with not drinking at all (odds ratio [OR] 0.48, 95% CI 0.39-0.59, p < 0.001, exposed cases n = 616). Effects were observed in a similar direction across disease subtypes, with the strongest association in the late-onset MG group (onset ≥50 years). Although neither cigarette smoke nor use of Swedish snuff affected the disease risk of the whole group, subset specific effects were observed. Smoking at onset was associated with an increased risk of early-onset MG (EOMG, onset 18-49 years; OR 1.60, 95% CI 1.17-2.20, p = 0.003, n = 133), which was accentuated in acetylcholine receptor antibody-positive EOMG (OR 2.08, 95% CI 1.34-3.25, p = 0.001, n = 74). Use of Swedish snuff, which contains high levels of nicotine, at disease onset was also associated with an increased risk of EOMG (OR 1.61, 95% CI 1.02-2.54, p = 0.039, n = 43).

DISCUSSION: We observed an inverse correlation of MG risk and alcohol consumption. Furthermore, smoking and the use of Swedish snuff at disease onset were positively associated with EOMG. We recognize limitations related to retrospective data and limited number of available controls. However, multiple sensitivity analyses were performed supporting the robustness of our results.