Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomised trial. FIN-RACo trial group.
BACKGROUND
The treatment of rheumatoid arthritis should aim at clinical remission. This multicentre, randomised trial with 2-year follow-up sought evidence on the efficacy and tolerability of combination therapy (sulphasalazine, methotrexate, hydroxychloroquine, and prednisolone) compared with treatment with a single disease-modifying antirheumatic drug, with or without prednisolone, in the treatment of early rheumatoid arthritis.


METHODS
199 patients were randomly assigned to two treatment groups. 195 started the treatment (97 received combination and 98 single drug therapy). Single-drug therapy in all patients started with sulphasalazine; in 51 patients methotrexate was later substituted. Oral prednisolone was required by 63 patients. The primary outcome measure was induction of remission. Analyses were intention to treat.


RESULTS
87 patients in the combination group and 91 in the single-therapy group completed the trial. After a year, remission was achieved in 24 of 97 patients with combination therapy, and 11 of 98 with single-drug therapy (p=0.011). The remission frequencies at 2 years were 36 of 97 and 18 of 98 (p=0.003). Clinical improvement (American College of Rheumatology criteria of 50% clinical response) was achieved after 1 year in 68 (75%) patients with combination therapy, and in 56 (60%) using single-drug therapy (p=0.028), while at the 2-year visit 69 and 57 respectively (71% vs 58%, p=0.058) had clinically improved. The frequencies of adverse events were similar in both treatment groups.


CONCLUSIONS
Combination therapy was better and not more hazardous than single treatment in induction of remission in early rheumatoid arthritis. The combination strategy as an initial therapy seems to increase the efficacy of the treatment in at least a proportion of patients with early rheumatoid arthritis.
Möttönen
T
T
Division of Rheumatology, Turku University Central Hospital, Finland. timo.mottonen@tyks.fi
Hannonen
P
P
Leirisalo-Repo
M
M
Nissilä
M
M
Kautiainen
H
H
Korpela
M
M
Laasonen
L
L
Julkunen
H
H
Luukkainen
R
R
Vuori
K
K
Paimela
L
L
Blåfield
H
H
Hakala
M
M
Ilva
K
K
Yli-Kerttula
U
U
Puolakka
K
K
Järvinen
P
P
Hakola
M
M
Piirainen
H
H
Ahonen
J
J
Pälvimäki
I
I
Forsberg
S
S
Koota
K
K
Friman
C
C
D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006886:Hydroxychloroquine / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D011239:Prednisolone / Q000009:adverse effects / Q000627:therapeutic use; D012074:Remission Induction; D012460:Sulfasalazine / Q000009:adverse effects / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D018501:Antirheumatic Agents; D012460:Sulfasalazine; D006886:Hydroxychloroquine; D011239:Prednisolone; D008727:Methotrexate