| 1. |
- Burkill, S., et al.
(författare)
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MS and the association of the DQB1*0302 allele with pain
- 2019
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 25:Suppl. 2, s. 437-438
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: There is an established association between multiple sclerosis (MS) and pain treatment, in particular neuropathic pain. Murine models have confirmed an association between carriage of the DQB1*0302 allele and development of neuropathic pain-like behavior after peripheral nerve injury. Observational studies in patients with spinal disc herniation identified an association between the DQB1*0302 allele and pain, indicating a possible link in humans. This HLA allele has not been previously investigated for its influence on susceptibility to pain in MS patients.Aim: To determine whether the DQB1*0302 genotype is associated with pain in MS patients or member of the general population without MS.Methods: Three Swedish studies (EIMS, GEMS and IMSE) were combined in which enrolled MS patients were matched with 1-2 randomly selected individuals without MS by sex, age and region of residence. Register data was obtained and prescriptions for pain and neuropathic pain were identified as proxy measures for pain. Blood samples were collected and genotyped. Individuals were included if genotype data were available (MS=3877, non-MS=4548). Logistic regression had pain medication use as the outcome, to examine associations with genotype, stratified by MS status.Results: Homo- or heterozygous MS patients with the DQB1*0302 allele had no significantly increased risk of pain (adjusted OR 1.02, 95% CI 0.85-1.23) or neuropathic pain (OR 1.14, 0.97-1.34) compared with MS patients without the allele. Non-MS comparators carrying at least one allele had an increased risk of pain (OR 1.18, 1.03-1.35). Additionally, a zygosity effect appeared present particularly for women in the non-MS cohort, as homozygous individuals had a higher risk of pain compared with heterozygotes. No association was observed for MS patients.Conclusions: The DQB1*0302 allele was associated with increased risk of pain among the non-MS cohort. Zygocity also impacted on pain risk in this cohort, particularly for women. The same was not observed in MS patients, for which no increased risk was detected. In view of previous data, immune functions seem to be involved in the development of pain and the observed associa-tion is likely due to peripheral nerve injuries or peripheral neu-ropathies. The allele was not associated with pain in the MS population, which often stems from CNS lesions.
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| 2. |
- Castelo-Branco, A., et al.
(författare)
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Treatment patterns in patients with multiple sclerosis : a single hospital cohort study in Sweden
- 2021
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 27:Suppl. 2, s. 732-732
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: An increasing number of disease-modifying therapies (DMT) for multiple sclerosis (MS) has led to switching between treatments.Objectives: In a Swedish MS cohort study, we analysed switching treatment patterns, including prescribed symptomatic medications, before and after an MS diagnosis.Methods: A national incident MS cohort diagnosed in 2008–2016 in the Swedish National Patient Register was linked to the national Prescribed Drug Register. A subcohort in the electronic medical records (EMR) of the Karolinska University Hospital was analysed for medication usage.Results: Patients with an MS diagnosis in the EMR cohort (n=1289) were identified (female, 68.2%; mean age (standard deviation), 38.8 (12.2) years). Prescribed symptomatic medications in the year before cohort entry included analgesics (23.2%), antidepressants (13.9%), opioids (13.4%), systemic corticosteroids (11.2%), and anxiolytics (10.0%). In the 4 years after cohort entry, medications included analgesics (65.2%), systemic antibacterials (55.9%), anti-inflammatory and antirheumatics (50.1%), antidepressants (34.8%), anxiolytics (21.1%), antiepileptics (19.1%) and ophthalmic drugs (16.6%). Of 1289 patients, 1040 were prescribed a DMT (80.7%). Median time (months, interquartile range) to first usage of new DMTs by age group was 1.71, 0.82–4.30 (<40 years); 1.87, 0.95–7.00 (40–59 years); and 3.96, 1.15–12.16 (⩾60 years). The most common DMTs (n=patients) were first-line (n=1054): interferons (55.9%), rituximab (15.7%), dimethyl fumarate (9.1%), natalizumab (7.4%), glatiramer acetate (7.1%), fingolimod (3.5%); second-line (n=551): rituximab (29.4%), natalizumab (19.4%), dimethyl fumarate (17.6%), fingolimod (16.3%), glatiramer acetate (7.8%), interferons (3.1%), teriflunomide (2.2%); third-line (n=184): rituximab (51.1%), natalizumab (13.0%), interferons (9.8%), fingolimod (9.8%), dimethyl fumarate (6.0%).Conclusions: These data indicate high usage of prescribed symp-tomatic medications before and after the MS diagnosis, which may indicate the consequences of prodromal and early sympto-matic MS. Most patients were treated with a DMT within months of diagnosis, with predominant initial use of interferons, and switching to more potent agents in later lines of therapy. Prescribing patterns are changing and expected to evolve further with earlier use of powerful agents.
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| 3. |
- Montgomery, Scott, 1961-, et al.
(författare)
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Infections in patients with multiple sclerosis : a nationwide cohort study in Sweden
- 2019
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 25:Suppl. 2, s. 388-388
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Previous studies suggest that susceptibility to infections is not raised among multiple sclerosis (MS) patients in general, but certain specific infections, such as those of the urinary or respiratory tract, are more common in patients with higher disability. However, contemporary MS cohorts to a higher degree are treated with newer disease-modifying treatments (DMTs) that exert stronger effects on the immune defence. Here we investigated the rate of infections in patients before and after MS diagnosis as compared with a matched MS-free population.Methods: Incident MS patients diagnosed in 2008-2016 were identified in the Swedish National Patient Register. MS patients were matched to 10 MS-free individuals by age, sex, and region of residence. Incidence rates per 10,000 person-years and incidence rate ratios (IRRs) of first infection by site and type were calculated after the MS diagnosis date.Results: In total, 6,602 MS patients were identified and compared with 61,828 without MS (female, 69%; median age, 40 years). During the year before MS diagnosis, MS patients showed higher proportions of urinary and kidney infections, meningitis and encephalitis, and bacterial infections compared with the MS-free cohort.After MS diagnosis, an increased risk of non-serious (IRR 1.65; 95% CI 1.56-1.75) and serious (admitted to hospital) infections (IRR 2.59; 95% CI 2.33-2.89) was detected among MS patients relative to the MS-free cohort. The risk of some bacterial (IRR 2.23; 95% CI 1.98-2.52) and some viral infections (IRR 1.70; 95% CI 1.48-1.96) was higher in MS patients of both sexes while only males showed an increased risk of fungal infections (IRR 1.91; 95% CI 1.26-2.89). Relative to the MS-free cohort, MS patients had an increased risk of all infection types, such as meningitis and encephalitis (IRR 6.16; 95% CI 4.47-8.48), other opportunistic infections (IRR 2.72; 95% CI 2.08-3.55), urinary and kidney infections (IRR 2.44; 95% CI 2.24-2.66), herpes virus (IRR 2.32; 95% CI 1.77-3.05), pneumonia and influenza (IRR 1.92; 95% CI 1.66-2.23), and skin infections (IRR 1.89; 95% CI 1.65-2.16).Conclusions: After MS diagnosis, patients had higher incidences of non-serious and serious infections compared with a cohort without MS. MS patients had an increased risk of being diagnosed during follow-up with most infection types compared with controls. This risk was particularly high for meningitis and encephalitis.
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| 4. |
- Montgomery, Scott, 1961-, et al.
(författare)
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Risk of osteoporosis and fractures in patients with multiple sclerosis : a nationwide cohort study in Sweden
- 2019
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 25:Suppl. 2, s. 387-388
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: While multiple sclerosis (MS) is usually diagnosed in young adults, many individuals living with the diagnosis are above age 40 years. Osteoporosis and fractures, which are morbidities generally associated with ageing but also physical inactivity, were determined in patients before and after MS diagnosis and compared with a matched MS-free population.Methods: Incident MS patients diagnosed in 2008-2016 were identified in the Swedish National Patient Register and matched with 10 MS-free individuals by age, sex, and region of residence. Incidence rates (IR) per 10,000 person-years and incidence rate ratios (IRRs; vs the MS-free cohort) of osteoporosis and fractures by sex and age at event were calculated after MS diagnosis based on ICD-10 codes from inpatient and outpatient specialist care.Results: In total, 6,602 MS patients were identified and compared with 61,828 without MS (female, 69%; median age, 40 years). Before MS diagnosis, MS patients showed significantly increased proportions of osteoporosis (0.5% vs 0.3%) and fractures (12.6% vs 11.4%) compared with the MS-free cohort.After diagnosis, MS patients had an increased risk of osteoporosis (IRR 1.69; 95% confidence interval [CI] 1.22-2.35). The increased risk of osteoporosis among MS patients was observed for both sexes (females, IRR 1.60; 95% CI 1.13-2.28 and males, IRR 2.56; 95% CI 1.04-6.31), as well as in the older age strata 40-59 years (IRR 2.39; 95% CI 1.47-3.89) and ⩾60 years (IRR 1.69; 95% CI 1.06-2.70), but not among those aged < 40 years. Similarly, an increased risk of fractures among MS patients (IRR 1.37; 95% CI 1.24-1.51) was shown for both females (IRR 1.40; 95% CI 1.25-1.58) and males (IRR 1.29; 95% CI 1.07-1.55), as well as the age strata 40-59 years (IRR 1.52; 95% CI 1.31-1.76) and ⩾60 years (IRR 1.92; 95% CI 1.58-2.33), but not those aged < 40 years.Conclusions: The risk of osteoporosis and fractures was moderately increased in MS patients of both sexes and in the older age groups, which may relate to physical inactivity and an increased risk of falls.
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| 5. |
- Piehl, F., et al.
(författare)
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Cardiovascular disease in patients with multiple sclerosis : a nationwide cohort study in Sweden
- 2019
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 25:Suppl. 2, s. 49-50
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: The cardiovascular disease (CVD) rate among multiple sclerosis (MS) patients has been shown to be elevated; however, studies involving more recently diagnosed patients are rare. Here we estimated the rate of CVD in patients before and after MS diagnosis as compared with a matched MS-free population.Methods: Incident MS patients diagnosed in 2008-2016 were identified in the Swedish National Patient Register. MS patients were matched with 10 MS-free individuals by age, sex, and region of residence. Incidence rates (IR) per 10,000 person-years (PY) and incidence rate ratios (IRR) of cardiovascular outcomes were calculated after MS diagnosis (equivalent date for those without MS) and among those with no history of CVD before this date.Results: In total, 6,602 MS patients and 61,828 without MS (female, 69%; median age, 40 years) were identified. Before MS diagnosis, patients showed higher proportions of stroke (2.0% vs 0.6%), transient ischaemic attack (TIA) (0.4% vs 0.2%) and peripheral vascular disease (0.3% vs 0.2%) compared with the MS-free cohort. The year before MS diagnosis, larger proportions were prescribed diuretics (8.4% vs 6.9%), peripheral vasodilators (1.4% vs 1.0%), lipid-modifying agents (5.6% vs 4.8%), and calcium channel blockers (3.7% vs 3.1%).After MS diagnosis, patients had a higher risk of major adverse cardiovascular events (MACE) (IRR 1.35; 95% confidence interval [CI] 1.06-1.71), heart failure (HF) (IRR 1.36; 95% CI 1.02-1.80), and TIA (IRR 1.59; 95% CI 1.05-2.42) compared with the MS-free cohort. The risk of bradycardia (IRR, 2.61; 95% CI 1.14-5.97) was higher only in MS patients with no history of CVD. CVD incidence rates in MS patients were comparable between sexes except for the HF rate, which was higher among males (28.28 per 10,000 PY, 95% CI 18.79-40.87) than females (11.81 per 10,000 PY, 95% CI 7.71-17.30). The relative risk of MACE (IRR 2.40; 95% CI 1.15-5.00), TIA (IRR 7.03; 95% CI 2.62 -18.87), HF (IRR 3.28; 95% CI 1.46-7.37), and bradycardia (IRR 4.51; 95% CI 1.54-13.20) were higher among younger MS patients (aged < 40 years at diagnosis).Conclusions: After MS diagnosis, MS patients showed an increased incidence of MACE, TIA, and HF compared with those without MS, irrespective of CVD history. The age-matched rela-tive risk was particularly high among younger MS patients. In particular, the relative risk of bradycardia was only higher among younger patients and patients with no history of CVD.
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| 6. |
- Piehl, F., et al.
(författare)
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Risk of comorbidity in patients with multiple sclerosis : a nationwide cohort study in Sweden
- 2019
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 25:Suppl. 2, s. 102-102
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Substantial progress in the treatment of multiple sclerosis (MS) has been made since the 1990s. However, the presence of comorbidity and the impact of treatment are less defined. Here we determined rates of comorbidity before and after MS diagnosis as compared with a matched MS-free population.Methods: A national incident MS cohort diagnosed in 2008-2016 was identified in the Swedish National Patient Register with data further linked to the national Prescribed Drug Register and Cause of Death Register. In addition, a sub-cohort of MS patients was identified in the electronic medical records (EMR) of the Karolinska University Hospital. MS patients were matched with and compared to 10 MS-free individuals by age, sex, and region of residence. Incidence rates (IR) per 10,000 person-years and incidence rate ratios (IRR) of comorbidities were calculated after MS diagnosis.Results: In total, 6,602 MS patients were identified in the national cohort and were compared with 61,828 MS-free controls (female, 69%; median age, 40 years), while a sub-cohort from one hospital of 1,289 patients had a MS diagnosis recorded in EMR and was compared with 11,721 individuals without MS (female, 68%; median age, 37 years). The national MS cohort had higher proportions before MS diag-nosis compared with MS-free controls of autoimmune disease (1.3% vs 0.7%), bladder dysfunction (1.2% vs 0.2%), retinal disorders (2.4% vs 1.2%) and epilepsy (1.5% vs 0.8%). Similar patterns were observed for the single-hospital cohort, except for epilepsy. Bipolar disorder was more common among single-hospital MS patients (1.6% vs 0.7%).After MS diagnosis, patients in the national cohort had higher IR compared with MS-free controls of autoimmune disease (IRR 3.60; 95% confidence interval [CI], 2.88-4.51), bladder dysfunction (IRR 47.44; 95% CI, 36.81-61.14) and epilepsy (IRR 2.36; 95% CI, 1.75-3.17). Similar patterns were observed in the single-hospital cohort. Toxic liver disease was higher (IRR 3.51; 95% CI 1.37-8.98) in the MS cohort in the national cohort only, while bipolar disorder was higher only in the single-hospital cohort (IRR 1.88; 95% CI 1.10-3.22).Conclusions: Before a diagnosis of MS, patients already displayed an increased rate of comorbidity compared with MS-free controls. After diagnosis, patients with MS continued to display increased risk of several comorbidities, some of which may be explained by surveillance bias due to more frequent contact with healthcare.
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| 7. |
- Smith, K. A., et al.
(författare)
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Rapid discontinuation of baclofen as a treatment for spasticity among MS patients with incident and prevalent diagnoses
- 2022
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 28:Suppl. 3, s. 663-663
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Baclofen is the first line drug choice for spasticity; a common MS feature influencing function and quality of life. Its prescription and discontinuation patterns among persons with MS (pwMS) are described incompletely.Objective & Aim: To characterize baclofen prescription patterns in a nationwide cohort study of people with prevalent (pMS) and incident (iMS) MS.Method: Data was linked from the Swedish MS register and national health registers for PwMS aged 18-65 years at diagnosis. Baclofen initiation was identified using the Prescription Drug Register excluding prescriptions from 1 July 2005—30 June 2006 (1st year of the register) and before MS diagnosis, to identify new prescriptions. Follow-up was from first dispensation until discontinuation, 31 Dec 2014 or death. Discontinuation was defined as no renewed prescription within gaps of 90, 150, or 180 days from last dispensation. Failure functions were plotted and Cox regression estimated hazard ratios.Results: A total of 188 (10%) of iMS (N=1826) and 628 (19%) of pMS (N=3519) received a new baclofen prescription. Discontinuation among iMS and pMS was similar using different time gaps: 49% (CI 0.42-0.57) iMS and 51% (CI 0.48-0.56) pMS discontinued within 150 days and approx. 90% discontinued overall. Approx. 65% of individuals discontinued within 1-year and 80% by 2-years. iMS with progressive course were treated for longer than relapsing course, and though similar among pMS differences between courses were less evident. Stratifying by EDSS (0-2.5, 3.0-5.5 and 6+) at baclofen initiation showed that PwMS with higher EDSS persisted longer than EDSS 0-2.5 but discontinuation was high among all groups. Cox regression showed EDSS associated with discontinuation, with iMS of EDSS 3-5.5 and 6+ 72% (CI 0.44-1.16) and 61% (CI 0.35-1.05); pMS 78% (CI 0.59-1.03) and 65% (CI 0.49-0.85) less likely to discontinue. No other MS characteristics (duration, age, course, sex, diagnosis/onset age), depression or seizures were associated. Though not statistically significantly associated, females and those with a progressive course were less likely to discontinue.Conclusions: Baclofen has similarly high discontinuation rates among patients with iMS and pMS, possibly reflecting low tolerability or efficacy. Only increased disability indicated by higher EDSS was associated with longer baclofen persistence highlighting the need for more tolerable and efficacious pharmacological treatments for spasticity in PwMS.
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| 8. |
- Smith, K., et al.
(författare)
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Central nervous system infections in adolescence and MS risk after age 20 years
- 2020
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 26:3 Suppl., s. 42-42
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Infectious agents in MS etiology have been previously investigated. Theories of pathogenic mechanisms include molecular mimicry or activation of macrophages and natural killer cells with subsequent infiltration of the blood brain barrier. Epstein-Barr virus (EBV) infection often signaled by infectious mononucleosis (IM) is a notable MS risk factors, but other infections including Chlamydia pneumoniae, among others, are also associated with MS. Adolescence is a potentially critical period for susceptibility MS and asso-ciations with exposures in adolescence such as concussion, pneumonia, BMI, and EBV/IM have been found. No studies to our knowledge have examined CNS infection as a risk factor for MS.Objectives: To determine if CNS infection in childhood (age 0-11 years) or adolescence (age 11-20) is associated with MS risk after age 20 years.Methods: A cohort born in Sweden between 1970-1994 followed until 31 December 2014, was identified using the Total Population Register, excluding those diagnosed with MS before age 20 years (y) (N=2,422,969). ICD codes from the National Patient Register identified diagnoses of MS after age 20y (n=4,022) (two or more diagnoses), and CNS infection (bacterial and viral) before age 20y. Diagnoses of IM, pneumonia, and other bacterial or viral infections were identified. Infections were classified as present/absent at 0-10y or 11-20y. Cox regression was used to determine associations of CNS infection with MS, with follow-up from age 20y to first MS diagnosis, adjusting for gastrointestinal, genitourinary, respiratory, skin, other infections, sex and parental socioeconomic position.Results: CNS infection before age 11y was not associated with MS. CNS infection in adolescence was statistically significantly associated with increased MS risk producing an adjusted hazard ratio of 2.80 (95%CI 1.90-4.12). Excluding encephalomyelitis (as this includes acute disseminated encephalitis, often a precursor of MS) the estimate was 1.85 (95%CI 1.11-3.07): an accurate estimate of risk lies between these two hazard ratios. Further adjustment for other infec-tions did not alter the estimates notably.Conclusions: This novel finding of CNS infection in adolescence associated with MS risk suggests such infections may cause cellular damage in the CNS triggering autoimmune processes pertinent to multiple sclerosis pathogenesis. It also adds to the evidence of a critical susceptibility period in adolescence for MS initiation.
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