- Email: [email protected]
0482 Analysis of genetic variants of chemokines for association with multiple sclerosis
Poster Abstracts Conclusions: New methods enable clinicians to solve the main problems of existing scales without increasing patient burden. Item banks are not subject to floor and ceiling effects, are lffghly sensitive to change across the entire spectrum of disability, and will be invaluable tools for measuring patient outcomes in future clirfical trials.
0479 Is it Raseh to compare thee on another scale? Hobart, JC L2'3'4, Styles, IM 3, Baron, R a, Thompson, AJ 4, Andrich, D ~.
2Peninsula Medical School, Plymouth, UK,"2School of Education, Murdoch University, Perth, WA; 3Institute of Neurology, Queen Square, London, UK Introduction: Patient completed rating scales are increasingly used as outcome measures in clinical trials. One major problem is that there are many different scales, the results of which cannot be compared directly, even though they clearly measure a common health construct (e.g. physical functioning). Tiffs inability to compare studies and undertake meta-analyses, is not new and was one of the driving forces behind the development of sophisticated psychometric methods which enabled scales measuring a common construct to be equated. Our aim was to determine if four scales purporting to measure physical functioning could be equated on the sanre metric so that their results can be compared directly. Methods: Data were Rasch analysed from 563 people with multiple sclerosis (MS) who completed: the physical functioning scales of the MS Impact Scale (MSIS-29) and Short Form 36 health survey (SF-36), the Functional Assessment of MS (FAMS) mobility scale, and the selfreport Barthel Index (BI). Results: Analyses indicated that the four scales measure a common construct, but measure at different places, and across different ranges, of the physical functioning variable. It was possible to construct a common metric on which all possible scores from all four scales could be compared. Conclusion: The four scales studied measure physical functioning, and their results have been equated. Soplffsticated methods offer investigators the opportunity to overcome the limitations of rating scales and advance outcomes measurement for clinical trials of neurological diseases. Future clinical trials have the potential to benefit from these methods. 0480 Evaluating injection site pain and reactions during interferon beta treatment: results from the bright (Betaferon ® versus Rebif ~ investigating higher tolerability) study
Bauul, K 1, O'Leary, Ca. 1Klinik Hennigsdorf, Hennigsdorf, Germany:
2Southern General Hospital NHS Trust, Glasgow, UK Background: Interferon beta-lb (IFNB-lb; Betaferon(r)) subcutaneously (sc) every other day (cod) is an effective, well-tolerated treatment for relapsing forms of multiple sclerosis (MS). Data suggest that high-dose, high-frequency IFNB (250 meg IFNB-Ib sc eod or 44 mcg IFNB- l a s c [Rebif(r)] three times weekly [tiw]) is more effective than low-dose, low-fiequency IFNB-la intranruscularly (Avonex(r)). Injection site reactions (ISRs) can occur with IFNB therapy, but their frequency tends to decrease with time. Evidence also suggests injection site reactions (ISRs) and injection site pain (lISP) are more frequent and severe with sc IFNB-la than IFNB-lb. BRIGHT will assess the frequency and severity of ISRs and ISP associated with these treamrents in patients with relapsing-remitting MS. Methods: BRIGHT is a multicentre, international, prospective, observational study comparing 250 meg I F N B - l b sc eod with 44 meg I F N B - l a sc tiw. Patients must have started treatment within 3 months prior to recruitment and completed the titration phase. Autoinjector use is recommended. Patients self-admirfister injections, assess pain severity for 15 consecutive injections using a 0 100 m r visual analogue scale diary immediately after injection, and 30 and
Tuesday, November 8, 2005
$221
60 minutes post-injection, and rate pain quality after the 1st, 7th and 15th injections. Investigators determine the occurrence and severity of ISRs. Results: To date > 247 patients have been recruited from 43 centres in 11 European countries. Data fi'om at least 300 patients will be analysed. Conclusion: BRIGHT will determine the influence of ISP on patient satisfaction with therapy and highlight any differences in ISRs and ISP between these two treatments. 048I Fatigue and SleepineSs in Multiple Sclerosis: Pilot Study Beran R 1;2, Ainley L A E 1, Holland G a. 1Strategic Health
Evaluators, Sydney, Australia; ant Luke's Hospital Complex, Brisbane, Australia Background: MS related fatigue is a major disability without therapeutic options. Tiffs pilot study exanrines nature and causes of MS fatigue, hypothesising altered sleep architecture especially periodic limb movement in sleep (PLMS) as causative. Method: Following ethics approval, 12 people with MS consented to complete blinded Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS) and Fatigue hnpact Scale (FIS) plus polysomnography (PSG), drug screelffng and multiple sleep latency test (MSLT). Equal subsets, based on ESS, were compared for demographics, MS criteria and PSG. A control cohort of 14 fatigued non-MS patients were compared for demographics and PSG. Comparative analyses for ESS plus FSS and FIS sub division, FSS alone and FSS with FIS (excluding ESS) were performed. Results: Similar subgroup demographics and MS criteria suggested an homogeneous MS population without confounding MSLT or drugs. Comparison between the 12 MS and 14 fatigued non-MS revealed differences for: minimum oxygenation (13 - 0.0316); PLMS with arousal (PLMA) (p - 0.0387); time in non R E M sleep (]3 _ 0.0308); latency to R E M (]3 _ 0.0101); and mean duration hypopneas/ apnoeas (13 -- 0.0453). Comparing fatigued MS with non-MS cohorts (divided re ESS) eliminated differences suggesting fatigue as the relevant variable. Comparing MS subsets (divided re ESS) indicated trends to altered sleep architecture re RDI, duration of hypopneas/ apnoeas and PLMS with significance for P L M A (]3 -- 0.0447). Siglffficance was eliminated when dividing re ESS plus FSS and FIS, FSS alone or FSS plus FIS alone, although supporting tire ESS based division. Conclusion: ESS (examining sleepiness) offers a more definitive tool for fatigue in MS. Sleep disorders, especially PLMA, suggest therapeutic options. Larger studies, including treatnlent evaluation, are warranted.
0482 Analysis of Genetic Variants of Chemokines for Association with Multiple Sclerosis Bugeja, M 1, Booth, D 1, Bennetts, B 2, Heard, R 1, Stewart, G 1. 1Institute for Immunology and Allergy Research, Westmead Millennium Institute, University of Sydney, NSW, Australia; 2Department of Molecular Genetics, The Children's Hospital at tVestmead, University of Sydney, NSW, Australia Background: Multiple sclerosis (MS) is a complex genetic disease, believed to result fi'om the interaction of a number of genes, each with modest effect. A fundamental feature of MS pathogenesis is the migration of autoanrigen-spedfic lymphocytes to the central nervous system, under the control of chemokines. The chemokine genes are predominantly localised to two genetic clusters: one on chromosome 17q11.2-12, the other at 4q13.3-21.1. Both regions have been implicated in a nmnber of genome-wide MS association screens, and several of the chemokines are differentially expressed in MS patients compared to healthy controls. We have comprehensively scanned
0479 Is it Raseh to compare thee on another scale? Hobart, JC L2'3'4, Styles, IM 3, Baron, R a, Thompson, AJ 4, Andrich, D ~.
2Peninsula Medical School, Plymouth, UK,"2School of Education, Murdoch University, Perth, WA; 3Institute of Neurology, Queen Square, London, UK Introduction: Patient completed rating scales are increasingly used as outcome measures in clinical trials. One major problem is that there are many different scales, the results of which cannot be compared directly, even though they clearly measure a common health construct (e.g. physical functioning). Tiffs inability to compare studies and undertake meta-analyses, is not new and was one of the driving forces behind the development of sophisticated psychometric methods which enabled scales measuring a common construct to be equated. Our aim was to determine if four scales purporting to measure physical functioning could be equated on the sanre metric so that their results can be compared directly. Methods: Data were Rasch analysed from 563 people with multiple sclerosis (MS) who completed: the physical functioning scales of the MS Impact Scale (MSIS-29) and Short Form 36 health survey (SF-36), the Functional Assessment of MS (FAMS) mobility scale, and the selfreport Barthel Index (BI). Results: Analyses indicated that the four scales measure a common construct, but measure at different places, and across different ranges, of the physical functioning variable. It was possible to construct a common metric on which all possible scores from all four scales could be compared. Conclusion: The four scales studied measure physical functioning, and their results have been equated. Soplffsticated methods offer investigators the opportunity to overcome the limitations of rating scales and advance outcomes measurement for clinical trials of neurological diseases. Future clinical trials have the potential to benefit from these methods. 0480 Evaluating injection site pain and reactions during interferon beta treatment: results from the bright (Betaferon ® versus Rebif ~ investigating higher tolerability) study
Bauul, K 1, O'Leary, Ca. 1Klinik Hennigsdorf, Hennigsdorf, Germany:
2Southern General Hospital NHS Trust, Glasgow, UK Background: Interferon beta-lb (IFNB-lb; Betaferon(r)) subcutaneously (sc) every other day (cod) is an effective, well-tolerated treatment for relapsing forms of multiple sclerosis (MS). Data suggest that high-dose, high-frequency IFNB (250 meg IFNB-Ib sc eod or 44 mcg IFNB- l a s c [Rebif(r)] three times weekly [tiw]) is more effective than low-dose, low-fiequency IFNB-la intranruscularly (Avonex(r)). Injection site reactions (ISRs) can occur with IFNB therapy, but their frequency tends to decrease with time. Evidence also suggests injection site reactions (ISRs) and injection site pain (lISP) are more frequent and severe with sc IFNB-la than IFNB-lb. BRIGHT will assess the frequency and severity of ISRs and ISP associated with these treamrents in patients with relapsing-remitting MS. Methods: BRIGHT is a multicentre, international, prospective, observational study comparing 250 meg I F N B - l b sc eod with 44 meg I F N B - l a sc tiw. Patients must have started treatment within 3 months prior to recruitment and completed the titration phase. Autoinjector use is recommended. Patients self-admirfister injections, assess pain severity for 15 consecutive injections using a 0 100 m r visual analogue scale diary immediately after injection, and 30 and
Tuesday, November 8, 2005
$221
60 minutes post-injection, and rate pain quality after the 1st, 7th and 15th injections. Investigators determine the occurrence and severity of ISRs. Results: To date > 247 patients have been recruited from 43 centres in 11 European countries. Data fi'om at least 300 patients will be analysed. Conclusion: BRIGHT will determine the influence of ISP on patient satisfaction with therapy and highlight any differences in ISRs and ISP between these two treatments. 048I Fatigue and SleepineSs in Multiple Sclerosis: Pilot Study Beran R 1;2, Ainley L A E 1, Holland G a. 1Strategic Health
Evaluators, Sydney, Australia; ant Luke's Hospital Complex, Brisbane, Australia Background: MS related fatigue is a major disability without therapeutic options. Tiffs pilot study exanrines nature and causes of MS fatigue, hypothesising altered sleep architecture especially periodic limb movement in sleep (PLMS) as causative. Method: Following ethics approval, 12 people with MS consented to complete blinded Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS) and Fatigue hnpact Scale (FIS) plus polysomnography (PSG), drug screelffng and multiple sleep latency test (MSLT). Equal subsets, based on ESS, were compared for demographics, MS criteria and PSG. A control cohort of 14 fatigued non-MS patients were compared for demographics and PSG. Comparative analyses for ESS plus FSS and FIS sub division, FSS alone and FSS with FIS (excluding ESS) were performed. Results: Similar subgroup demographics and MS criteria suggested an homogeneous MS population without confounding MSLT or drugs. Comparison between the 12 MS and 14 fatigued non-MS revealed differences for: minimum oxygenation (13 - 0.0316); PLMS with arousal (PLMA) (p - 0.0387); time in non R E M sleep (]3 _ 0.0308); latency to R E M (]3 _ 0.0101); and mean duration hypopneas/ apnoeas (13 -- 0.0453). Comparing fatigued MS with non-MS cohorts (divided re ESS) eliminated differences suggesting fatigue as the relevant variable. Comparing MS subsets (divided re ESS) indicated trends to altered sleep architecture re RDI, duration of hypopneas/ apnoeas and PLMS with significance for P L M A (]3 -- 0.0447). Siglffficance was eliminated when dividing re ESS plus FSS and FIS, FSS alone or FSS plus FIS alone, although supporting tire ESS based division. Conclusion: ESS (examining sleepiness) offers a more definitive tool for fatigue in MS. Sleep disorders, especially PLMA, suggest therapeutic options. Larger studies, including treatnlent evaluation, are warranted.
0482 Analysis of Genetic Variants of Chemokines for Association with Multiple Sclerosis Bugeja, M 1, Booth, D 1, Bennetts, B 2, Heard, R 1, Stewart, G 1. 1Institute for Immunology and Allergy Research, Westmead Millennium Institute, University of Sydney, NSW, Australia; 2Department of Molecular Genetics, The Children's Hospital at tVestmead, University of Sydney, NSW, Australia Background: Multiple sclerosis (MS) is a complex genetic disease, believed to result fi'om the interaction of a number of genes, each with modest effect. A fundamental feature of MS pathogenesis is the migration of autoanrigen-spedfic lymphocytes to the central nervous system, under the control of chemokines. The chemokine genes are predominantly localised to two genetic clusters: one on chromosome 17q11.2-12, the other at 4q13.3-21.1. Both regions have been implicated in a nmnber of genome-wide MS association screens, and several of the chemokines are differentially expressed in MS patients compared to healthy controls. We have comprehensively scanned