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- 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. |
- 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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