DMARDs combination or biological therapy in rheumatoid arthritis patients

Carlos Abud-Mendoza, MD,

Other Contributors:

July 18, 2012

Dear Editor,

We read with interest the paper by De Jong PH et al.,(1) a single blinded clinical trial which reports that triple disease modifying antirheumatic drugs (DMARDs) induction therapy is better than methotrexate (MTX) monotherapy in early rheumatoid arthritis (RA).

Our Hospital is located in San Luis Potosí (Mexico) and our cohort includes low income patients without any opportunities for biological therapy. Our induction therapy for early RA patients almost always includes 2-3 DMARDs and low dosage prednisone.

Recently, we evaluated 125 patients with RA that had been under stable treatment with biological therapy (BT) or > 3 DMARD (DMARDs combination) for at least a complete year before the evaluation for this study. Seventy six patients were under biologics and 49 on DMARDs combination. In both groups we evaluated clinical disease activity and ultrasound remission (UR) using DAS28; musculoskeletal ultrasounds (twelve-joint simplified power doppler ultrasonographic assessment)(2) UR was defined as when there was absence of power doppler activity in evaluated joints. Clinical remission was defined as a DAS28 score <2.6.(3).

Demographic characteristics were between BT (n=76) and DMARDs combination (n=49): women 68 vs 43 (p=0.766), mean age (years) 51.3 vs 48.9 (p=0.3), and evolution of the disease in years 14.7 vs 5.7 (p<0.0001). The combination group received methotrexate 94.7%, sulfazalacine 97.8%, antimalarial therapy 95.5% and prednisone 71.4%. The BT group received methotrexate (94.7%) and prednisone (56.6%). DAS 28 remission was achieved in 43.4% of BT group and 24.5% of DMARDs combination group (p= 0.03); of these, sixteen patients (48%) of BT and 4 (33%) of DMARDs combination achieved UR (p=0.055). Our study and results from tREACH emphasize the benefit of triple therapy with DMARDs. Moreover, our results with power doppler emphasize that it is possible to achieve UR in patients using non-biological therapy, although we observed that more patients receiving BT than DMARDs reached UR De Jong et al, emphasize that the DMARDs combination decreases the number of patients requiring BT. We think that DMARDs combination for early RA is an excellent option for developing countries including Mexico; moreover, maybe it is also a good option for developed countries considering the cost of BT.(4)

We recognize that rheumatologists are influenced by medical information with scientific evidence, but most of these studies have been supported by pharmaceutical industries. Annual earnings were recently reported to exceed 30 billion dollars (USD) for biological therapy including adalimumab, etanercept, infliximab and rituximab.(5) In Mexico it is estimated that fewer than 2% of RA patients receive BT, probably due to the high cost of this therapy.(5)

Post-marketing studies, head to head including >3 DMARDs and BT that compare benefit, safety, direct and indirect costs may provide better options for the therapy selection.


1. de Jong PH, Hazes JM, Barendregt PJ, et al. Induction therapy with a combination of DMARDs is better than methotrexate monotherapy: first results of the tREACH trial. Ann Rheum Dis. 2012. Epub 2012/06/09.

2. Naredo E, Rodriguez M, Campos C, et al. Validity, reproducibility, and responsiveness of a twelve-joint simplified power doppler ultrasonographic assessment of joint inflammation in rheumatoid arthritis. Arthritis Rheum 2008;59(4):515-22. Epub 2008/04/03.

3. Fransen J, Creemers MC, Van Riel PL. Remission in rheumatoid arthritis: agreement of the disease activity score (DAS28) with the ARA preliminary remission criteria. Rheumatology (Oxford). 2004;43(10):1252-5. Epub 2004/07/09.

4. van Vollenhoven RF, Geborek P, Forslind K, et al. Conventional combination treatment versus biological treatment in methotrexate-refractory early rheumatoid arthritis: 2 year follow-up of the randomised, non-blinded, parallel-group Swefot trial. Lancet. 2012;379(9827):1712-20. Epub 2012/04/03.

5. Biologic drugs set to top 2012 sales. Nat Med. 2012;18(5):636. Epub 2012/05/09.

Conflict of Interest:

None declared

Conflict of Interest

None declared