Response-Driven Combination Therapy with Conventional Disease-Modifying Antirheumatic Drugs Can Achieve High Response Rates in Early Rheumatoid Arthritis with Minimal Glucocorticoid and Nonsteroidal Anti-Inflammatory Drug Use

https://doi.org/10.1016/j.semarthrit.2007.02.001Get rights and content

Objectives

To assess the safety and efficacy of combination therapy in recent-onset rheumatoid arthritis (RA), with dose adjustments determined by response, in a clinic setting over 3 years.

Methods

Disease-modifying antirheumatic drug (DMARD)-naïve patients with RA of median duration of 12 weeks (n = 61) attending an early arthritis clinic were treated with methotrexate, sulfasalazine, hydroxychloroquine, and fish oil. Dosage adjustments and additions of further DMARDs were contingent on response to therapy and tolerance. Outcome measures for efficacy were Disease Activity Score (DAS28), clinical remission, and modified Sharp radiographic score and for safety, adverse events, and DMARD withdrawal.

Results

At baseline, subjects had at least moderately active disease (mean ± SD DAS28 was 5.3 ± 1.1), impaired function as measured by the modified Health Assessment Questionnaire (mHAQ) (0.9 ± 0.5), and 37% had bone erosions. By 3 months, 29% were in remission; this increased to 54% at 3 years. The greatest fall in DAS28 and improvement in mHAQ scores occurred in the first 12 months. Erosions were detected in 62% at 3 years. The mean dose of parenteral glucocorticoid was equivalent to 0.1 mg/d of prednisolone. After 3 years, 48% remained on triple therapy; fish oil was consumed by 75% of patients, and 21% used nonsteroidal anti-inflammatory drugs. Gastrointestinal intolerance was the most frequent unwanted event (leading to DMARD withdrawal in 17 patients). Sulfasalazine was most frequently withdrawn (30%).

Conclusion

This implementation study demonstrates the feasibility, safety, and efficacy of combination therapy with inexpensive DMARDs, fish oil, and minimal glucocorticoid use, in routine clinical practice using predefined rules for dosage adjustment.

Section snippets

Inducement of Early Referrals

Correspondence and newsletters were sent to family physicians in the practice area to encourage early referral of patients with recent-onset polyarthritis.

Subjects

Consecutive patients presenting between September 1998 and February 2002 with recent-onset polyarthritis to the Early Arthritis Clinics at the Royal Adelaide and The Queen Elizabeth Hospitals as well as private practices of participating rheumatologists were followed prospectively for 3 years. The study was approved by the Research Ethics

Patient Characteristics

Of 84 consecutive patients presenting with recent-onset polyarthritis to the Early Arthritis Clinic (Fig. 2), 18 did not meet entry criteria. A further 2 patients refused to participate in a research study and 3 refused MTX, so 61 received triple therapy and were followed for treatment safety for 3 years (Fig. 2). Of the 61 patients initiating triple therapy, 48 with disease duration of less than 6 months were included in a separate efficacy analysis. The characteristics of these patients at

Discussion

Our approach was designed to meet the individual needs of patients in an orderly process based on a predefined treatment plan that utilized, from the outset, a combination of DMARDs of established efficacy and included adjustments according to response and tolerance. The objective was to achieve early, high rates of disease suppression/remission with acceptable levels of toxicity. This report documents the feasibility and effectiveness of the approach in a routine clinic setting. After a period

Acknowledgments

Many thanks to Leah McWilliams for clinical metrology and data collection, Cindy Hall for data collection and analysis, and Sue Lester for data analysis. Drs. Sam Whittle, Sally Cox, Eliza Pontifex, Fin Cai, Tim Lu, and Debashish Danda assisted with patient care and data collection. A proportion of the fish oil was kindly provided as a gift from Berg LipidTech, Aarlesund, Norway. This work was supported by National Health and Medical Research Council of Australia.

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