The effect of interferon beta-1a on spasticity in primary progressive multiple sclerosis
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《神经病学神经外科学杂志》
Institute of Neurology, University College London, Queen Square, London, UK
Correspondence to:
A J Thompson
Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK; a.thompson@ion.ucl.ac.uk
It has been suggested that spasticity may be increased in primary progressive multiple sclerosis (PPMS) following treatment with interferon beta.1 In an open study using the Ashworth Scale and a reflex scale, Bramanti et al measured change in spasticity in 19 subjects treated with interferon beta-1b and in 19 untreated subjects. An increase in spasticity during treatment was seen in 68% of the treated participants compared with 11% of the untreated participants. To investigate this phenomenon further, we conducted a retrospective analysis of the spasticity studied in the recently published randomised controlled trial of interferon beta-1a in PPMS.2
We randomised 50 subjects to receive weekly for two years an intramuscular injection of either interferon beta-1a 30 μg (15 subjects); or interferon beta-1a 60 μg (15 subjects); or placebo (20 subjects). Following completion of the study, the clinical notes of all cases were reviewed and the occurrence of spasticity documented. Spasticity was not a predetermined outcome, but symptomatic spasticity had been recorded in the notes by the blinded treating physician, including both post-dose spasticity and any independent, sustained increase in the level of spasticity. Any increase in anti-spasticity medication was also documented. Statistical analysis was carried out on an intention to treat basis. Comparisons were made between the placebo and combined interferon group and the individual treatment groups using Fisher’s exact test.
Two years of follow up were completed by 49 participants; 43 completed the study on treatment, with the dose having been halved in seven patients.2 There were no significant differences in sustained increase in spasticity, post-dose spasticity, or anti-spasticity medication, when the combined interferon group was compared with the placebo group (table 1). No significant differences were seen between the individual treatment groups and the placebo group, except that a sustained increase in spasticity occurred less commonly in the group receiving interferon beta-1a 60 μg.
Table 1 Number of subjects experiencing an increase in spasticity
This study found no significant increase in spasticity in patients with PPMS treated with interferon beta-1a. There was a non-significant trend to an increase in post-dose spasticity in the interferon groups (33%) compared with the placebo group (15%). Transient increased spasticity following dosing with interferon beta has also been reported in secondary progressive and relapsing remitting MS.3,4 This phenomenon is not surprising, given that worsening of existing spasticity in association with intercurrent factors such as fever is a common experience in MS. However, there was no suggestion of a sustained increase in spasticity or increased requirements for anti-spasticity medication.
There are obvious limitations to this study, most notably the retrospective analysis. It is difficult to comment on the discrepancy between our findings and those of Bramanti et al, because of the different trial designs and the use of different types of interferon beta. Further investigation of the effect of interferon beta on spasticity would require a prospective randomised controlled study.
ACKNOWLEDGEMENTS
This study was funded by a generous grant from Biogen.
SML and AJT have been reimbursed by Biogen for attending or speaking at conferences.
References
Bramanti P, Sessa E, Rifici C, et al. Enhanced spasticity in primary progressive MS patients treated with interferon beta-1b. Neurology 1998;51:1720–3.
Leary SM, Miller DH, Stevenson VL, et al. Interferon beta-1a in PPMS: an exploratory, randomized controlled trial. Neurology 2003;60:44–51.
European Study Group on Interferon ?-1b in Secondary Progressive MS. Placebo-controlled multicentre randomized trial of interferon ?–1b in treatment of secondary progressive multiple sclerosis. Lancet 1998;352:1491–7.
Frese A, Bethke F, Ludemann P, et al. Enhanced spasticity in primary progressive MS patients treated with interferon ?-1b. Neurology 1999;53:1892–3, (letter).(S M Leary and A J Thompso)
Correspondence to:
A J Thompson
Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK; a.thompson@ion.ucl.ac.uk
It has been suggested that spasticity may be increased in primary progressive multiple sclerosis (PPMS) following treatment with interferon beta.1 In an open study using the Ashworth Scale and a reflex scale, Bramanti et al measured change in spasticity in 19 subjects treated with interferon beta-1b and in 19 untreated subjects. An increase in spasticity during treatment was seen in 68% of the treated participants compared with 11% of the untreated participants. To investigate this phenomenon further, we conducted a retrospective analysis of the spasticity studied in the recently published randomised controlled trial of interferon beta-1a in PPMS.2
We randomised 50 subjects to receive weekly for two years an intramuscular injection of either interferon beta-1a 30 μg (15 subjects); or interferon beta-1a 60 μg (15 subjects); or placebo (20 subjects). Following completion of the study, the clinical notes of all cases were reviewed and the occurrence of spasticity documented. Spasticity was not a predetermined outcome, but symptomatic spasticity had been recorded in the notes by the blinded treating physician, including both post-dose spasticity and any independent, sustained increase in the level of spasticity. Any increase in anti-spasticity medication was also documented. Statistical analysis was carried out on an intention to treat basis. Comparisons were made between the placebo and combined interferon group and the individual treatment groups using Fisher’s exact test.
Two years of follow up were completed by 49 participants; 43 completed the study on treatment, with the dose having been halved in seven patients.2 There were no significant differences in sustained increase in spasticity, post-dose spasticity, or anti-spasticity medication, when the combined interferon group was compared with the placebo group (table 1). No significant differences were seen between the individual treatment groups and the placebo group, except that a sustained increase in spasticity occurred less commonly in the group receiving interferon beta-1a 60 μg.
Table 1 Number of subjects experiencing an increase in spasticity
This study found no significant increase in spasticity in patients with PPMS treated with interferon beta-1a. There was a non-significant trend to an increase in post-dose spasticity in the interferon groups (33%) compared with the placebo group (15%). Transient increased spasticity following dosing with interferon beta has also been reported in secondary progressive and relapsing remitting MS.3,4 This phenomenon is not surprising, given that worsening of existing spasticity in association with intercurrent factors such as fever is a common experience in MS. However, there was no suggestion of a sustained increase in spasticity or increased requirements for anti-spasticity medication.
There are obvious limitations to this study, most notably the retrospective analysis. It is difficult to comment on the discrepancy between our findings and those of Bramanti et al, because of the different trial designs and the use of different types of interferon beta. Further investigation of the effect of interferon beta on spasticity would require a prospective randomised controlled study.
ACKNOWLEDGEMENTS
This study was funded by a generous grant from Biogen.
SML and AJT have been reimbursed by Biogen for attending or speaking at conferences.
References
Bramanti P, Sessa E, Rifici C, et al. Enhanced spasticity in primary progressive MS patients treated with interferon beta-1b. Neurology 1998;51:1720–3.
Leary SM, Miller DH, Stevenson VL, et al. Interferon beta-1a in PPMS: an exploratory, randomized controlled trial. Neurology 2003;60:44–51.
European Study Group on Interferon ?-1b in Secondary Progressive MS. Placebo-controlled multicentre randomized trial of interferon ?–1b in treatment of secondary progressive multiple sclerosis. Lancet 1998;352:1491–7.
Frese A, Bethke F, Ludemann P, et al. Enhanced spasticity in primary progressive MS patients treated with interferon ?-1b. Neurology 1999;53:1892–3, (letter).(S M Leary and A J Thompso)