Combination dmard therapy including corticosteroids in early rheumatoid arthritis
T.T. Möttönen1, P.J. Hannonen2, M. Boers3
1Department of Medicine, Division of Rheumatology, Turku University Central Hospital, Turku; 2Department of Medicine, Jyväskylä Central Hospital, Jyväskylä, Finland; and 3Department of Clinical Epidemiology and Biostatistics, Free University Amsterdam, The Netherlands
ABSTRACT
A number of reports indicating the growing acceptance of simultaneous therapy with
multiple disease-modifying antirheumatic drugs (DMARDs), as well as the use of more
aggressive treatment measures in the early phases of disease to combat rheumatoid
arthritis (RA), have appeared during the last decade. However, only a few randomized
controlled clinical trials have been conducted on the use of DMARD combinations in early
RA. We review these trials in this article.
In two separate one-year studies combination therapy with sulphasalazine (SSZ) and
methotrexate (MTX) seemed to offer no benefits compared to either drug used as
monotherapy. On the other hand, the DMARD combinations so far proven to be superior to
single DMARDs have initially also included a corticosteroid component.
In the COBRA study (Combinatietherapie Bij Reumatoide Artritis) the combination of SSZ (2
gm/day), MTX (7.5 mg/week for 40 weeks), and prednisolone (Prd) (initially 60 mg/day,
tapered in 6 weekly steps to 7.5 mg/day and stopped after 28 weeks) compared to SSZ alone
(2 gm/day) resulted in significantly better clinical outcomes at week 28. Although the
difference in clinical response between the treatment arms was lost at week 58, the
progression of joint damage remained statistically significantly slower at week 80 in the
patients initially assigned to the combination therapy.
Furthermore, in the FIN-RACo trial (Finnish Rheumatoid Arthritis Combination Therapy
Trial), therapy using a "tailored-steps" strategy with SSZ (1 - 2 gm/day), MTX
(7.5 - 15 mg/week), hydroxychloroquine (300 mg/day), and Prd (up to 10 mg/day) yielded a
significantly increased remission rate and less peripheral joint damage at two years than
the single DMARD treatment strategy (initially SSZ 2 gm/day), with or without Prd. Adverse
effects in both study arms were comparable.
Two additional preliminary reports (in abstract form) suggest that intensive local therapy
in the form of intra-articular injections added to single or combination therapy improves
both local and systemic disease control, with increased remissions and less damage.
Although still preliminary, these results should encourage the rheumatological community
to treat selected RA patients with DMARD combinations from the very start.
Key words
Early rheumatoid arthritis, therapy, DMARD, methotrexate, sulphasalazine, combination,
corticosteroids.
Please address reprint requests and correspondence to: Dr. Timo Möttönen, Turku
University Central Hospital, Division of Rheumatology, Paimio Hospital, FIN-21540 Paimio,
Finland.
E-mail: timo.mottonen@tyks.fi
Clin Exp Rheumatol 1999; 17 (Suppl. 18): S59 - S65.
© Copyright Clinical
and Experimental Rheumatology
1999.