Supplementary webappendix

Supplementary webappendix
This webappendix formed part of the original submission and has been peer reviewed.
We post it as supplied by the authors.
Supplement to: Ravnborg M, Sørensen PS, Andersson M, et al. Methylprednisolone
in combination with interferon beta-1a for relapsing-remitting multiple sclerosis
(MECOMBIN study): a multicentre, double-blind, randomised, placebo-controlled,
parallel-group trial. Lancet Neurol 2010; published online June 8. DOI:10.1016/S14744422(10)70132-0.
MECOMBIN investigators:
Denmark Skleroseklinikken N2082 at University Hospital of Copenhagen, Copenhagen (Mads
Ravnborg, Per Soelberg Sørensen); Department of Neurology at Hilleroed Hospital, Hilleroed (Michael
Brocksgaard Jensen), Department of Neurology at Glostrup Hospital, Glostrup (Jette Frederiksen);
Department of Neurology at Roskilde University Hospital, Roskilde (Anne Heltberg); Scleroseklinik at
Southwest Jutland Hospital Esbjerg, Vejle and Sønderborg (Egon Stenager); Scleroseklinikken at the
University Hospital of Aarhus, Aarhus C (Thor Petersen); Department of Neurology at Holstebro
Hospital, Holstebro (Karen Nygaard Madsen). Sweden Neurologiska kliniken at Karolinska University
Hospital, Huddinge, Stockholm (Jan Hillert); Neurocenter at St Goerans Hospital, Stockholm (Yngve
Hallström);
Neurocentrum
at
Norrland’s
University
Hospital,
Umeaa
(Anders
Svenningsson);
Neurologkliniken at Central Regional Hospital, Karlstad (Rune Johansson); Neurologkliniken at
Danderyd’s
Hospital,
Stockholm
(Claes
Martin);
Medicinmottagningen
at
Trelleborg
Hospital,
Trelleborg (Tryggve Karlsson); Forskningsenhet at Sahlgrenska University Hospital, Goeteborg (Jan
Lycke); Neurologkliniken at Karolinska University Hospital, Solna, Stockholm (Magnus Andersson);
Neurologkliniken at Malmoe University Hospital, Malmö (Ursula Heldmann); Neurokliniken at BB
Neurokonsult AB, Helsingborg (Svend Marup Jensen). Norway Department of Neurology at Ullevaal
University Hospital, Oslo (Elisabeth Gulowsen Celius); Department of Neurology at Innlandet Hospital
Trust, Lillehammer (Tone Hognestad); Department of Neurology at Vestfold Hospital Trust, Toensberg
(Mats Fredriksen); Department of Neurology at Foerde Central Hospital, Foerde (Wenche Telstad);
Department of Neurology at Buskerud Hospital Trust, Drammen (Astrid Edland); Department of
Neurology at Namdal Hospital, Namsos (Ole-Petter Dahl); Nevro Oest at St. Olavs Hospital, Trondheim
University Hospital, Trondheim (Harald Hovdal); Department of Neurology at Nordland Central
Hospital, Bodoe (Rolf Salvesen); Nevrologisk poliklinikk at University Hospital in Oslo, Oslo (Halfdan
Kierulf); Neurologist, Fredrikstad (Bente Bjørnstad); Department of Neurology at Haukeland University
Hospital, Bergen (Kjell-Morten Myhr). Finland Department of Neurology at Tampere University
Hospital, Tampere (Irina Elovaara); Department of Neurology at Helsinki University Central Hospital,
Helsinki (Markus Färkkilä); Department of Neurology at Kuopio University Hospital, Kuopio (Tuula
Pirttilä); Department of Neurology at Hyvinkää Hospital, Hyvinkää (Esko Kinnunen); Department of
Neurology at Oulu University Hospital, OYS (Mauri Reunanen); Department of Neurology at Jyväskylä
Central Hospital, Jyvläskylä (Taneli Sarasoja). Belgium Erasme University Hospital, University of
Brussels, Brussels
(Emmanuel
Bartholomé);
Clinique
Saint-Pierre, Ottignies
(Michel
Dupuis);
Rehabilitation and Multiple Sclerosis Centre, Overpelt (Vande Gaer); Centre Hospitalier Regional de la
Citadelle, Liege (Alain Maertens); Department of Neurology at Elizabeth Hospital, Damme (Danny
Decoo). Netherlands MS Centrum Nijmegen, Nijmegen (PJH Jongen); St Lucas Andreas Hospital,
Amsterdam (WHJP Linssen); Amphia Hospital, Molengracht, Breda (EACM Sanders); Department of
Neurology at Medical Centre Leeuwarden, Leeuwarden (LGF Sinnige); Maxima Medical Center,
Veldhoven (PLI Dellemijn), Medical Centre Rijnmond-Zuid, Rotterdam (J Samijn). Switzerland
Inselspital University Hospital Bern, Bern (Heinrich Mattle); Kantonsspital St Gallen, St Gallen
(Norman Pietzki). UK Division of Clinical Neurology at University Hospital Queen's Medical Centre,
Nottingham (Cris Constantinescu).
Methylprednisolone
Placebo
p*
Dysgeusia
26 (17·0)
1 (0·6)
<0·0001
Flushing
25 (14·6)
0 (0)
<0·0001
Insomnia
47 (27·5)
7 (4·2)
<0·001
Dyspepsia
15 (8·8)
2 (1·2)
0·0033
Erythema
19 (11·1)
4 (2·4)
0·0033
Influenza like illness
78 (45·6)
96 (57·5)
0·0375
Palpitations
14 (8·2)
5 (3)
0·0665
Hypertension
13 (7·6)
5 (3)
0·1012
Oedema
9 (5·3)
3 (1·8)
0·1507
Sinusitis
5 (2·9)
10 (6·0)
0·2611
Urinary tract infection or cystitis
19 (11·1)
26 (15·6)
0·2906
Myalgia
14 (8·2)
8 (4·8)
0·2964
Limb pain
8 (4·7)
13 (7·8)
0·3415
Depression
11 (6·4)
16 (9·6)
0·3757
Acne
12 (7·0)
7 (4·2)
0·3781
Pyrexia
19 (5·8)
6 (3·6)
0·4020
Weight increase
9 (5·3)
5 (3·0)
0·4334
Liver function tests abnormal
7 (4·1)
11 (6·6)
0·4358
Back pain
10 (5·8)
14 (8·4)
0·4706
Nausea
11 (6·4)
7 (4·2)
0·5095
Paresthesia
6 (3·5)
9 (5·4)
0·5591
Fatigue
24 (14·0)
19 (11·4)
0·5795
Influenza
17 (9·9)
14 (8·4)
0·7720
Upper respiratory tract infection
10 (5·8)
9 (5·4)
0·8728
Abdominal pain upper
10 (5·8)
9 (5·4)
0·8728
Arthralgia
15 (8·8)
13 (7·8)
0·8924
Nasopharyngitis
27 (15·8)
28 (16·8)
0·9193
Rash
10 (5·8)
11 (6·6)
0·9361
Headache
29 (17·0)
28 (16·8)
0·9609
Webtable 1: Adverse events that occurred in at least 5% of any group
Data are number (%). *Two-sample test for equality of proportions with continuity correction,
two-sided.
Methylprednisolone
Placebo
Baseline
Month 39
Baseline
Month 39
Units
Mean
SD
Mean
SD
Mean
SD
Mean
SD
Haemoglobin
g/L
52·86
61·24
52·63
61·33
51·56
61·18
54·18
62·07
Thrombocytes
10**9/L 255·00 64·20
268·50 67·93
267·00 63·17
269·70 68·29
Basophilocytes
10**9/L 0·21
0·48
0·68
5·86
0·14
0·27
0·13
0·48
Eosinophilocytes
10**9/L 0·70
1·24
0·49
0·85
0·52
0·85
0·33
0·54
Lymphocytes
10**9/L 9·21
13·33
8·01
18·93
10·80
37·38
4·93
8·79
Monocytes
10**9/L 2·39
3·66
1·86
3·21
1·98
2·99
1·40
2·58
Neutrocytes
10**9/L 17·88
24·89
13·21
20·94
17·44
24·94
11·65
21·35
Leucocytes
10**9/L 6·33
1·85
6·45
2·25
6·37
1·84
6·22
1·99
Sodium
mmol/L
139·90 7·46
139·10 11·91
138·90 14·76
138·00 17·07
Potassium
mmol/L
4·90
8·17
5·86
12·77
4·07
0·54
6·28
16·32
Creatinine
umol/L
62·90
27·59
58·08
27·55
62·73
26·61
60·64
25·11
Albumin
g/L
163·40 246·70 156·60 243·70 138·30 229·30 147·40 230·90
Urea
mmol/L
11·01
37·95
13·73
46·25
11·83
46·30
14·24
54·96
Bilirubin
umol/L
8·82
4·73
8·81
7·64
9·95
5·90
9·51
4·89
Aspartate aminotransferase ukat/L
18·29
13·82
18·38
14·91
17·77
15·35
18·67
23·93
Alanine transaminase
ukat/L
25·34
26·91
21·64
20·89
21·38
20·55
22·89
41·63
Alkaline phosphatase
ukat/L
60·83
48·48
48·97
31·24
55·92
43·27
44·40
29·95
Glucose
mmol/L
9·58
18·93
10·20
19·97
7·97
14·88
7·87
15·84
Blood
Haemoglobin A1C
0·05
0·01
0·05
0·01
0·07
0·30
0·05
0·01
Urine
Haemoglobin
arb unit
0·15
0·66
0·12
0·48
0·14
0·51
0·10
0·46
Albumin
arb unit
0·19
1·20
0·05
0·22
0·04
0·26
0·03
0·16
Ketones
arb unit
0·01
0·11
0·01
0·09
0·01
0·11
0·02
0·13
Glucose
arb unit
0·01
0·08
0·00
0·00
0·00
0·00
0·00
0·00
Webtable 2: Blood and urine tests

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