Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomised trial

Möttönen, Timo; Hannonen, Pekka; Leirisalo‐Repo, Marjatta; Nissilä, M; Kautiainen, Hannu; Korpela, Markku; Laasonen, Leena; Julkunen, Heikki; Luukkainen, R; Vuori, Kaisa; Paimela, Leena; Blåfield, Harri; Hakala, M; Ilva, Kirsti; Yli-Kerttula, U; Puolakka, Kari; Järvinen, Pentti A.; Hakola, Mikko; Piirainen, Heikki; Ahonen, J; Pälvimäki, Ilppo; Forsberg, S; Koota, K; Friman, Claes

doi:10.1016/s0140-6736(98)08513-4

Cited by 709 publications

(427 citation statements)

References 25 publications

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“…From April 1993 to May 1995, a total of 199 DMARD-naive patients with recent-onset (symptom duration Ͻ2 years; median 6 months) RA were admitted to this multicenter, parallel-group, randomized study comparing the efficacy and tolerability of therapy with a combination of DMARDs (simultaneous sulfasalazine, methotrexate, hydroxychloroquine, and prednisolone) with the efficacy and tolerability of therapy with a single DMARD (initially, sulfasalazine, with or without prednisolone). The study has been described in detail previously (4).…”

Section: Methodsmentioning

confidence: 99%

“…More patients receiving combination therapy than those receiving monotherapy reached clinical remission (37% versus 18%; P ϭ 0.03). The increase in Larsen scores was ϳ2-fold in RA patients in the single-DMARD group compared with those in the combination-DMARD group (4).…”

mentioning

confidence: 87%

“…therapy (2)(3)(4)(5). In the Dutch Combinatietherapie Bij Reumatoïde Artritis (COBRA) study, the initial aggressive step-down treatment of early RA with high-dose prednisolone, methotrexate, and sulfasalazine for 6 months, in comparison with monotherapy with sulfasalazine, regardless of the subsequent antirheumatic therapy, showed sustained suppression of the rate of radiologic progression that was detectable even after the 4-5-year followup period (6).…”

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confidence: 99%

“…We have previously reported the 2-year clinical results of the prospective, randomized Finnish Rheumatoid Arthritis Combination Therapy (FIN-RACo) trial comparing the efficacy and tolerability of therapy with a combination of 3 DMARDs with that of DMARD monotherapy in 195 patients with early active RA (4). A total of 178 patients completed the 2-year followup trial.…”

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confidence: 99%

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Retardation of joint damage in patients with early rheumatoid arthritis by initial aggressive treatment with disease‐modifying antirheumatic drugs: Five‐year experience from the FIN‐RACo study

Korpela¹,

Laasonen²,

Hannonen³

et al. 2004

Arthritis & Rheumatism

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Objective. To evaluate the long-term frequency of disease remissions and the progression of joint damage in patients with early rheumatoid arthritis (RA) who were initially randomized to 2 years of treatment with either a combination of 3 disease-modifying antirheumatic drugs (DMARDs) or a single DMARD.Methods. In this multicenter prospective followup study, a cohort of 195 patients with early, clinically active RA was randomly assigned to treatment with a combination of methotrexate, sulfasalazine, hydroxychloroquine, and prednisolone or with a single DMARD (initially, sulfasalazine) with or without prednisolone. After 2 years, the DMARD and prednisolone treatments became unrestricted, but were still targeted toward remission. The long-term effectiveness was assessed by recording the frequency of remissions and the extent of joint damage seen on radiographs of the hands and feet obtained annually up to 5 years. Radiographs were assessed by the Larsen score.Results. A total of 160 patients (78 in the combination group and 82 in the single group) completed the 5-year extension study. At 2 years, 40% of the patients in the combination-DMARD group and 18% in the single-DMARD group had achieved remission (P < 0.009). At 5 years, the corresponding percentages were 28% and 22% (P not significant). The median Larsen radiologic damage scores at baseline, 2 years, and 5 years in the combination-DMARD and single-DMARD groups were 0 and 2 (P ‫؍‬ 0.50), 4 and 12 (P ‫؍‬ 0.005), and 11 and 24 (P ‫؍‬ 0.001), respectively.Conclusion. Aggressive initial treatment of early RA with the combination of 3 DMARDs for the first 2 years limits the peripheral joint damage for at least 5 years. Our results confirm the earlier concept that triple therapy with combinations of DMARDs contributes to an improved long-term radiologic outcome in patients with early and clinically active RA.Rheumatoid arthritis (RA) is a chronic, potentially disabling disease characterized by synovial inflammation, with subsequent cartilage and bone destruction leading to joint malalignment. An abundance of evidence indicates the benefits of early intervention with disease-modifying antirheumatic drugs (DMARDs) on the disease course and outcome (1). Some recent studies clearly show that treatment of early RA with combinations of DMARDs is well tolerated and provides better clinical response than treatment with DMARD monoSupported by the Finnish Office for Health Care Technology Assessment.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 87%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Retardation of joint damage in patients with early rheumatoid arthritis by initial aggressive treatment with disease‐modifying antirheumatic drugs: Five‐year experience from the FIN‐RACo study

Korpela¹,

Laasonen²,

Hannonen³

et al. 2004

Arthritis & Rheumatism

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225

106

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“…While no single agent was proven to be enough to control disease progression, current acceptable therapy for rheumatoid arthritis is aimed to attenuate disease activity with a combination of disease-modifying anti-rheumatic drugs such as methotrexate, sulfasalazine, leflunomide, hydroxychloroquine, cyclosporin, azathioprine, etc. (34)(35)(36). The purpose of a combination therapy is to obtain synergistically therapeutic effects of drugs with different immunomodulatory mechanisms and, in the meantime, to reduce side effects from each drug by decreasing their dosages.…”

Section: Herbs Used In Autoimmune Diseasementioning

confidence: 99%

The Immunopharmaceutical Effects and Mechanisms of Herb Medicine

Huang¹,

Lin

Liao

et al. 2008

Cell Mol Immunol

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In recent years, studies on evaluation of the therapeutic and toxic activity of herbal medicinal products became available and popular. The advances in modern biotechnology have led to discovery of many new active constituents. However, it is a constant challenge to establish the pharmacological basis for efficacy and safety of herbal medicinal products. A better understanding of the effects and bioavailability of phytopharmaceuticals can help in discovering suitable and rational therapies. In this review, we present the bioavailability studies in immune system that has been conducted for some of the more important or widely used phytopharmaceuticals. Furthermore, various new drug targets worthy of using for drug development in immunomodulating herbal medicine area and their regulatory mechanisms are also discussed. Adverse effects, drug interactions, and contraindications are also discussed which show that caution should be exercised when combining phytopharmaceuticals with chemically derived pharmaceutical components. Cellular & Molecular Immunology. 2008;5(1):23-31.

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Cost-effectiveness of Adding Magnetic Resonance Imaging to Rheumatoid Arthritis Management

Suter¹,

Fraenkel²,

Braithwaite³

2011

Arch Intern Med

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Background Early, aggressive treatment of rheumatoid arthritis (RA) improves outcomes but confers increased risk. Risk stratification to target aggressive treatment of high-risk individuals with early RA is considered important to optimize outcomes while minimizing clinical and monetary costs. Some advocate the addition of magnetic resonance imaging (MRI) to standard RA risk stratification with clinical markers for patients early in the disease course. Our objective was to determine the incremental cost-effectiveness of adding MRI to standard risk stratification in early RA. Methods Using a decision analysis model of standard risk stratification with or without MRI, followed by escalated standard treatment protocols based on treatment response, we estimated 1-year and lifetime quality-adjusted life-years, RA-related costs, and incremental cost-effectiveness ratios (with MRI vs without MRI) for RA patients with fewer than 12 months of disease and no baseline radiographic erosions. Inputs were derived from the published literature. We assumed a societal perspective with 3.0% discounting. Results One-year and lifetime incremental cost-effectiveness ratios for adding MRI to standard testing were $204 103 and $167 783 per quality-adjusted life-year gained, respectively. In 1-way sensitivity analyses, model results were insensitive to plausible ranges for every variable except MRI specificity, which published data suggest is below the threshold for MRI cost-effectiveness. In probabilistic sensitivity analyses, most simulations produced lifetime incremental cost-effectiveness ratios in excess of $100 000 per quality-adjusted life-year gained, a commonly cited threshold. Conclusion Under plausible clinical conditions, adding MRI is not cost-effective compared with standard risk stratification in early-RA patients.

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Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomised trial

Cited by 709 publications

References 25 publications

Retardation of joint damage in patients with early rheumatoid arthritis by initial aggressive treatment with disease‐modifying antirheumatic drugs: Five‐year experience from the FIN‐RACo study

Retardation of joint damage in patients with early rheumatoid arthritis by initial aggressive treatment with disease‐modifying antirheumatic drugs: Five‐year experience from the FIN‐RACo study

The Immunopharmaceutical Effects and Mechanisms of Herb Medicine

Cost-effectiveness of Adding Magnetic Resonance Imaging to Rheumatoid Arthritis Management

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