Randomised comparison of initial triple DMARD therapy with methotrexate monotherapy in combination with low-dose glucocorticoid bridging therapy; 1-year data of the tREACH trial.
OBJECTIVE
To compare 1-year clinical efficacy of (1) initial triple disease-modifying antirheumatic drug therapy (iTDT) with initial methotrexate (MTX) monotherapy (iMM) and (2) different glucocorticoid (GC) bridging therapies: oral versus a single intramuscular injection in early rheumatoid arthritis.


METHODS
In a single-blinded randomised clinical trial patients were randomised into three arms: (A) iTDT (methotrexate+sulfasalazine+hydroxychloroquine) with GCs intramuscularly; (B) iTDT with an oral GC tapering scheme and (C) MTX with oral GCs similar to B. Primary outcomes were (1) area under the curve (AUC) of Health Assessment Questionnaire (HAQ) and Disease Activity Score (DAS) and (2) the proportion of patients with radiographic progression.


RESULTS
281 patients were randomly assigned to arms A (n=91), B (n=93) or C (n=97). The AUC DAS and HAQ were respectively -2.39 (95% CI -4.77 to -0.00) and -1.67 (95% CI -3.35 to 0.02) lower in patients receiving iTDT than in those receiving iMM. After 3 months, treatment failure occurred less often in the iTDT group, resulting in 40% fewer treatment intensifications. The difference in treatment intensifications between the arms required to maintain the predefined treatment goal remained over time. No differences were seen between the two GC bridging therapies. Respectively 21%, 24% and 23% of patients in arms A, B and C had radiographic progression after 1 year. Patients receiving iTDT had more adjustments of their medication owing to adverse events than those receiving iMM.


CONCLUSIONS
Treatment goals are attained more quickly and maintained with fewer treatment intensifications with iTDT than with iMM. However, no difference in radiographic progression is seen. Both GC bridging therapies are equally effective and, therefore, both can be used.


BACKGROUND
ISRCTN26791028.
Department of Rheumatology, University Medical Center, Rotterdam, The Netherlands.
P H
PH
de Jong
Department of Rheumatology, University Medical Center, Rotterdam, The Netherlands.
J M
JM
Hazes
Department of Rheumatology, Maasstad Hospital, Rotterdam, The Netherlands.
H K
HK
Han
Department of Rheumatology, Sint Francicus Gasthuis Hospital, Rotterdam, The Netherlands.
M
M
Huisman
Department of Rheumatology, Sint Francicus Gasthuis Hospital, Rotterdam, The Netherlands.
D
D
van Zeben
Department of Rheumatology, Vlietland Hospital, Schiedam, The Netherlands.
P A
PA
van der Lubbe
Department of Rheumatology, Vlietland Hospital, Schiedam, The Netherlands.
A H
AH
Gerards
Department of Rheumatology, Albert Schweitzer Hospital, Dordrecht, The Netherlands.
B
B
van Schaeybroeck
Department of Rheumatology, Admiraal de Ruyter Hospital, Goes & Vlissingen, The Netherlands.
P B
PB
de Sonnaville
Department of Rheumatology, Admiraal de Ruyter Hospital, Goes & Vlissingen, The Netherlands.
M V
MV
van Krugten
Department of Rheumatology, University Medical Center, Rotterdam, The Netherlands.
J J
JJ
Luime
Department of Rheumatology, University Medical Center, Rotterdam, The Netherlands Department of Rheumatology, Maasstad Hospital, Rotterdam, The Netherlands.
A E
AE
Weel
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy*; D018450:Disease Progression; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D006886:Hydroxychloroquine / Q000627:therapeutic use*; D007273:Injections, Intramuscular; D008137:Longitudinal Studies; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D011859:Radiography; D016037:Single-Blind Method; D012460:Sulfasalazine / Q000627:therapeutic use*; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D005938:Glucocorticoids; D012460:Sulfasalazine; D006886:Hydroxychloroquine; D008727:Methotrexate
DMARDs (synthetic); Early Rheumatoid Arthritis; Rheumatoid Arthritis; Treatment