Triple DMARD Therapy Vs. Methotrexate Monotherapy: Which Is Best in Treating Early Rheumatoid Arthritis?

Released: 18-Oct-2013 11:40 AM EDT
Embargo expired: 26-Oct-2013 4:30 PM EDT
Source Newsroom: American College of Rheumatology (ACR)
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Citations American College of Rheumatology Annual Scientific Meeting

Newswise — SAN DIEGO — Using a combination of three traditional disease-modifying antirheumatic drugs for treating recent-onset rheumatoid arthritis is more efficient than a monotherapy approach using methotrexate, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in San Diego.

Rheumatoid arthritis (RA) is a chronic disease that causes pain, stiffness, swelling, destruction leading to limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in other organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men.

Researchers in the Netherlands analyzed data on 281 patients with recent-onset RA who participated in a single-blinded, randomized clinical trial of RA therapies called the treatment in the Rotterdam Early Arthritis Cohort, or tREACH. Current guidelines do not recommend triple DMARD therapy of methotrexate, sulfasalazine and hydroxychloroquine for all newly diagnosed RA patients, although several clinical trials concluded that triple DMARD therapy was better than methotrexate monotherapy. Principal motive of disregarding triple DMARD therapy was the fact that the results were skewed by the use of glucocorticoids. There are also safety concern issues. The researchers sought to compare triple DMARD therapy with methotrexate, and to compare two methods of using glucocorticoids as bridging therapy.

“There is still debate on the most appropriate initial treatment regimen in patients with newly diagnosed RA,” explains Pascal de Jong, PhD, Department of Internal Medicine, Erasmus MC; and lead investigator of the study. “The most important discussion herein is that of initial methotrexate monotherapy versus a combination of DMARDs. Therefore, we investigated in our tREACH trial if triple DMARD therapy was better than methotrexate monotherapy independent of corticosteroids at treating RA symptoms.”

Participants were randomly split into three groups, each given different induction therapy regimens. The first group of 91 patients received triple DMARD therapy, or 25mg methotrexate per week, 2g of sulfasalazine per day and 400mg of hydroxycholorquine per day, in addition to 120mg of intramuscular glucocorticoids once. The second group of 93 patients received the same triple DMARD therapy with a tapered dose of oral glucocorticoids starting at 15mg per day. The third group of 97 patients received
25mg of methotrexate per week with a similarly tapered dose of oral glucocorticoids, starting at 15mg per day. Participants were 68 percent female and their average duration of having RA symptoms was 166 days. At the beginning of the study, 267 (95 percent) of the participants fulfilled the 2010 ACR Criteria for RA, 216 (77 percent) tested positive for anti-citrullinated protein antibodies (ACPA) and 48 (17 percent) showed evidence of joint erosions.

Participants were examined every three months to assess their progress, including measuring disease activity scores and collecting data from the Health Assessment Questionnaire. After 12 months of therapy, the researchers also analyzed X-ray progression.

The researchers found that after one year of triple DMARD therapy, patients had a better clinical effectiveness than monotherapy. The burden of the disease over time was less in groups receiving triple DMARD therapy compared with patients receiving methotrexate monotherapy. At three months, less treatment failure occurred in both the triple therapy groups, resulting in 40 percent fewer prescriptions of biologic drugs. This difference remained over time. No significant difference was seen between the two glucocorticoid bridging therapy approaches. Over the time period studied, 19 percent of the first group, 23 percent of the second group and 21 percent of the third group showed radiographic progression of their RA. No differences in serious side effects were found between the three groups.

The researchers concluded that for patients with early-onset RA, triple DMARD therapy is better than methotrexate monotherapy, even after one year of therapy, because treatment goals are attained faster and maintained with fewer biologic treatments. Either oral or intramuscular glucocorticoids may be equally effective as bridging therapy for these patients.

“We recommend initial triple DMARD therapy over methotrexate monotherapy as the first choice in newly diagnosed RA patients because treatment goals are attained faster and maintained with 40 percent fewer biological,” explains, Dr. de Jong.

Patients should talk to their rheumatologists to determine their best course of treatment.

The American College of Rheumatology is an international professional medical society that represents more than 9,000 rheumatologists and rheumatology health professionals around the world. Its mission is to advance rheumatology. The ACR/ARHP Annual Meeting is the premier meeting in rheumatology. For more information about the meeting, visit http://www.acrannualmeeting.org/ or join the conversation on Twitter by using the official hashtag: #ACR13

Editor’s Notes: Dr. de Jong will present this research during the ACR Annual Meeting at the San Diego Convention Center at 11:45 AM on Monday, October 28 in Room 6 A. Dr. de Jong will be available for media questions and briefing at 8:30 am Tuesday, October 29 in the on-site press conference room, 27
AB.

Abstract Number: 1693

Initial Triple DMARD Therapy Is More Efficient Than Methotrexate Monotherapy In Recent Onset Rheumatoid Arthritis; 1-Year Data Of a Randomized Clinical Trial (tREACH)

P.H.P. de Jong1, J.M.W. Hazes1, K.H. Han2, A.M. Huisman3, D. van Zeben3, P.A. van der Lubbe4, A.H. Gerards4, B. van Schaeybroeck5, P.B. de Sonnaville6, M.V. Krugten7, J.J. Luime1 and A.E.A.M. Weel2,

1Erasmus University Medical Center, Rotterdam, Netherlands, 2Maasstad Hospital, Rotterdam, Netherlands, 3Sint Franciscus Gasthuis, Rotterdam, Netherlands, 4Vlietland Hospital, Schiedam, Netherlands, 5Albert Schweitzer Hospital, Dordrecht, Netherlands, 6Admiraal de Ruyter hospital, Goes, Netherlands, 7Admiraal de Ruyter Hospital, Vlissingen, Netherlands

Background/Purpose: Recommended treatment for DMARD naïve patients is methotrexate (MTX) with or without glucocorticoids (GCs). Triple DMARD therapy however is not recommended, because well proven evidence of superior efficacy is suggested to be lacking. Furthermore possible drug toxicities might influence the physician's choice of induction therapy. Therefore, our aim is to compare one-year clinical efficacy of: (1) triple DMARD therapy vs. MTX mono-therapy and (2) oral GCs bridging therapy vs.
1 dose of intramuscular (im) GCs in patients with early RA.
Methods: The one-year data of single-blinded randomized clinical trial in patients with recent-onset arthritis (tREACH) were used. Patients were included who had a high probability (> 70%) of progressing to persistent arthritis, based on the prediction model of Visser. The Visser algorithm and 2010 criteria for RA have similar discriminative abilities to identify patients at risk of persistent arthritis at 1 year. Patients were randomized into 3 induction therapy strategies: (A) triple DMARD therapy (MTX 25 mg + sulfasalazine (SASP) 2 gr. + hydroxychloroquine (HCQ)) 400 mg with im GCs (Depomedrol 120mg), (B) triple DMARD therapy with an oral GCs tapering scheme (starting 15 mg) and (C) MTX with oral GCs similar to B. Treatment strategies were ‘tightly controlled', with patients being examined every 3 months and treatment decisions based upon the original DAS thresholds for low disease activity. We
investigated following response parameters over time: DAS, HAQ, using the area under the curve (AUC).
We also looked at radiographic progression after 12 months of therapy, medication usage and adverse events.

Results: A total of 281 patients were included in the high probability stratum and randomly assigned to (A) (n=91), (B) (n=93) or (C) (n=97). Patients were mostly females (68%) with an average symptom duration of 166 days (95% CI: 156 – 177). At baseline 267 (95%) of patients fulfilled the 2010 criteria for RA, 216 (77%) patients were ACPA positive and 48 (16%) patients had erosions. Over time disease activity and functional ability were respectively -2•39 (-4•77 to -0•00, 95%CI) and -1•67 (-3•35 to 0•02,
95%CI) lower in patients with triple DMARD therapy compared with MTX mono-therapy. After 3 months, less treatment failure occurred in the triple DMARD therapy groups, resulting in the prescription of 50% fewer biologicals. This difference remained over time. No differences were seen between both GC bridging therapies. Respectively 15%, 30%, and 18% of patients in arm A, B, and C had radiographic progression after 1 year. No differences in serious adverse events were seen.

Conclusion: In patients with early RA triple DMARD therapy is superior to MTX mono-therapy even after 12 months of therapy. Furthermore both intramuscular and oral GCs can be used as bridging therapy.

Disclosures: P. H. P. de Jong, None.
J. M. W. Hazes, None.
K. H. Han, None.
A. M. Huisman, None.
D. van Zeben, None.
P. A. van der Lubbe, None.
A. H. Gerards, None.
B. van Schaeybroeck, None. P. B. de Sonnaville, None. M. V. Krugten, None.
J. J. Luime, None.
A. E. A. M. Weel, None.


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