Early Combination Therapy in Rheumatoid Arthritis Slows Joint Damage Years Later

Initial treatment with a combination of disease-modifying anti-rheumatic drugs may be effective in slowing the progression of rheumatoid arthritis, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in San Francisco, Calif.

Rheumatoid arthritis, or RA as it is commonly called, is a chronic disease that causes pain, stiffness, swelling and limitations in the motion and function of multiple joints. While RA can affect any joint, the small joints in the hands and feet tend be involved more frequently than others. This produces a pattern of joint disease that rheumatologists regard as characteristic of RA. Inflammation can develop in other organs as well. Successful management of RA requires early diagnosis and, at times, aggressive treatment.

Patients with an established diagnosis of rheumatoid arthritis often begin treatment with disease-modifying anti-rheumatic drugs. DMARDs are frequently used in conjunction with low dose corticosteroids (such as prednisone), and have greatly improved the symptoms and function as well as the quality of life for the vast majority of patients with RA.

In an extension of a previously performed clinical study, researchers evaluated the progressive joint damage (shown through X-rays) in patients with RA—over a span of 11 years—to determine if an initial combination of three DMARDs would more effectively slow disease progression compared to initially taking one DMARD alone.

195 patients with early RA were randomly assigned to take either a combination of methotrexate, sulfasalazine, hydroxychloroquine and prednisolone, or just one DMARD (initially sulfasalazine alone, with or without prednisolone) for two years. After two years the use of DMARDs was unrestricted, but the therapy was still targeted to remission. To track disease progression, researchers took X-rays of the patients’ hands and feet at the beginning of the study and at two, five and 11 years into the study to measure the amount of damage that occurred in the joints.

They found that patients who started taking the combination of treatments at the start of their disease had less radiographic progression long-term than those who were initially treated with just one DMARD and that this difference was seen at two years and continued through 11 years.

“In early RA, initial combination treatment is more effective than initial single DMARD treatment in slowing the radiological progression even after a decade of RA, explains Vappu Rantalaiho, MD, specialist in rheumatology, Tampere University Hospital, department of internal medicine, Tampere, Finland, and lead investigator in the study. “These findings support the concept of the ‘window of opportunity’ for early, aggressive treatment in RA. They also emphasize that being inexpensive, these treatments are available for a large amount of RA patients worldwide.”

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

The ACR is an organization of and for physicians, health professionals, and scientists that advances rheumatology through programs of education, research, advocacy and practice support that foster excellence in the care of people with or at risk for arthritis and rheumatic and musculoskeletal diseases. For more information on the ACR’s annual meeting, see http://www.rheumatology.org/annual.

Editor’s Notes: Dr. Rantalaiho will present this research during the ACR Annual Scientific Meeting at the Moscone Center from 9:45 – 10:00 AM on Wednesday, October 29, in Room 102.
Presentation Number: 2043

Window of Opportunity in Early Rheumatoid Arthritis. Combination Therapy with FIN-RACo Strategy during the First 2 Years Translates into Less Joint Erosions in 11-year Radiographs

Vappu Rantalaiho1, Leena Laasonen2, Hannu Kautiainen3, Markku Korpela1, Pekka Hannonen4, Marjatta Leirisalo-Repo2, Timo Möttönen5. 1Tampere University Hospital, Tampere, Finland; 2Helsinki University Central Hospital, Helsinki, Finland; 3Rheumatism Foundation Hospital, Heinola, Finland; 4Jyväskylä Central Hospital, Jyväskylä, Finland; 5Turku University Hospital, Turku, Finland

Purpose: To evaluate the radiological progression during 11 years in patients with early rheumatoid arthritis (RA) initially treated either with a combination of 3 DMARDs or a single DMARD.

Methods: A cohort of 195 patients with early RA were randomized to a treatment with a combination of methotrexate, sulfasalazine, hydroxychloroquine and prednisolone (COMBI) or with a single DMARD (initially sulfasalazine) with or without prednisolone (SINGLE). After 2 years, the drug treatments became free, but were still targeted to remission. The radiographs of hands and feet were analyzed using the Larsen score at baseline, 2, 5 and 11 years.

Results: Sixty-five COMBI [60% women, 72% RF+, mean(SD) age at baseline 46(9) years] and 65 SINGLE [71% women, 65% RF+, 48(10) years] patients had radiographs of hands and feet available at baseline and at 11 years. At baseline the median (IQR) Larsen score was 0 (0 , 2) in COMBI and 2 (0 , 8) in SINGLE. The median (IQR) Larsen scores at baseline, 2, 5 and 11 years in both groups are shown in Figure 1. The median change in Larsen score from baseline to 11 years was 12 (95% CI: 4 to 16) in COMBI and 20 (95% CI: 12 to 30) in SINGLE (p=0.039, adjusted for age, sex, RF presence and baseline Larsen score). No erosive changes were present at 11 years in 18% of COMBI and 6% of SINGLE patients (p=0.059).

Conclusions: In early RA, patients treated initially with a combination of DMARDs during the first 2 years have less radiological progression even in long term than those randomized to monotherapy.

Disclosure Block: V. Rantalaiho, None; L. Laasonen, None; H. Kautiainen, None; M. Korpela, None; P. Hannonen, None; M. Leirisalo-Repo, None; T. Möttönen, None.

Source: American College of Rheumatology (ACR)