Table 26Disease activity and remission for early RA DMARD strategies

StudyStudy Design
Study PopulationComparison (dose)ResultsQuality Rating
Two Oral DMARDs+Corticosteroid vs. Oral DMARD
Boers et al., 1997;95 Landewe et al., 200296
155 (148)
56 weeks (5-year followup)
Multicenter; early RA; mean disease duration 4 monthsSSZ (2 g/day)+MTX (7.5 mg/day stopped after 40 weeks)+PNL (60 mg/day tapered over 28 weeks) vs. SSZPooled disease index: mean change better in combo group than SSZ alone at 28 weeks (1.4 vs. 0.8; P<0.0001) vs. no longer significant at 52 weeks (1.1 vs. 0.9; P=0.20)
(Pooled index included tender joint count, grip strength, ESR, VAS, MACTAR questionnaire)
Three Oral DMARDs+Corticosteroid vs. Oral DMARDs
Mottonen et al., 1999;97 Korpela et al., 200498
FIN-RACo study
24 months (5-year follow-up)
Multicenter; early RA; mean disease duration 7.3–8.6 monthsMTX (7.5 to 10 mg/week)+HCQ (300 mg/day)+SSZ (2 g/day)+PNL (5 to 10 mg/day) vs. DMARD (SSZ could be changed to MTX or 3rd line) ± PNLRemission (defined by ACR preliminary criteria modified by authors) higher in combination group (37.9% vs. 18.4%; P=0.011); ACR 50 higher in combination group (71% vs. 58%; P=0.058);
(5-year remission, NS, 28% vs. 22%; P=NS)
Three Oral DMARDs vs. Biologic+Oral DMARD
Van Vollenhoven et alo., 200999
Swefot trial
12 months
Swedish, multicenter; early RA; mean disease duration 6.2–6.3 monthsDAS-driven treatment; MTX up to 20mg /wk for 3–4 months, if DAS >3.2 randomized to MTX (up to 20 mg/week) +SSZ (1,000 mg twice/day)+HCQ (400 mg/day vs. MTX (up to 20 mg/week)+INF (3 mg/kg)EULAR good response lower in combination oral DMARD group (25% vs. 39%; P=0.0160Fair
Other Combination Strategies
Goekoop-Ruiterman et al., 2005;100 *Allaart et al., 2006;101 *Goekoop-Ruiterman et al., 2007;102 *van der Kooij, et al., 2009;103 *van der Kooij et al., 2009;196 *van der Kooij et al., 2008197
BeSt study
12 months
2 years
4 years
Multicenter; early RA; median duration between diagnosis and inclusion 2 weeks (IQR 1 to 5); median duration of symptoms 23 weeks (IQR 14 to 53)DAS-driven treatment;
1: sequential monotherapy starting with MTX (15 mg/week) vs. 2: stepped-up combination therapy (MTX, then SSZ, then HCQ, then PRED) vs. 3: combination with tapered high-dose PRED (60 mg/d to 7.5 mg/day) vs. 4: combination (MTX 25 to 30 mg/week) with INF (3 mg/kg every 8 weeks, per DAS, could be titrated to 10 mg/kg)
DAS ≤2.4: 53%, 64%, 71%, 74%; P=0.004 for 1 vs. 3; P=0.001 for 1 vs. 4; P=NS for other comparisons
Shorter time to DAS<2.4 for initial combination therapy groups (groups 3 and 4) than monotherapy groups (groups 1 and 2) (Median months; 3,3,9,9 P<0.001)
Similar remission among groups at 4 years (DAS<1.6; 50%, 41%, 38%, 42%; P=0.40)

New study added since last review.

BeST = Dutch acronym for Behandel Sstrategieen; COBRA = Combinatietherapie Bij Reumatoide Artritis; DAS = disease activity score; DMARD = disease modifying antirheumatic drug; ERA = early rheumatoid arthritis; ESR = erythrocyte sedimentation rate; ETN = etanercept; g = gram; HCQ = hydroxychloroquine; INF = infliximab; IQR = interquartile range; kilogram = kg; MACTAR = McMaster Toronto Arthritis Questionnaire mg = milligram; MTX = methotrexate; NR = not reported; NS = not significant; PNL = prednisolone; PRED = prednisone; RA = rheumatoid arthritis; RCT = randomized controlled trial; SSZ = sulfasalazine; VAS = visual analog scale; vs. = versus

From: Results

Cover of Drug Therapy for Rheumatoid Arthritis in Adults: An Update
Drug Therapy for Rheumatoid Arthritis in Adults: An Update [Internet].
Comparative Effectiveness Reviews, No. 55.
Donahue KE, Jonas DE, Hansen RA, et al.

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