1 The epidemiology of drug treatment failure in rheumatoid arthritis

Summary The length of time that patients remain on anti-rheumatic therapy is an important measure of the effectiveness of that therapy since length of time on therapy is a composite measure that accounts for sustained, positive therapeutic benefit as well as negative therapeutic benefit (e.g. adverse reactions, unacceptable costs and loss of efficacy), and accounts for noise (non-compliance, psychological factors, misunderstanding, etc.). Effectiveness is a measure of how well a drug does work, while efficacy, the measure used in randomized controlled trials, means that a drug can work; however, efficacy may or may not translate to usefulness in the clinic. To understand drug effectiveness we reviewed studies of 5809 patients receiving various SMARDs. The average median time on drug ranged from 1.10 to 2.27 years, excluding methotrexate, with shortest survival times falling to sulfasalzine (1.10) and auranofin (1.16), intermediate times to hydroxy-chloroquine (1.59), penicillamine (1.42), IM gold (1.40), and the longest time to azathioprine (2.27). Overall, excluding methotrexate, the average median survival time was 1.41 for 3998 patients. Median time on drug was 3.3 times greater for methotrexate than for all other drugs combined, averaging 4.61 years. Expressed in terms of ‘5-year survival,’ an average of 55.7% of patients remained on methotrexate 5 years after it was started. Better results noted here for methotrexate stand in contradistinction to short-term randomized controlled trials which find most SMARDs to be equal in efficacy. Other factors that may influence drug survival time include age, education level, psychological status, presence of fibromyalgia, rank order of SMARD administration, disease severity or corticosteroid administration. Studies can provide more information if they also measure clinical variables as well as time on drug, providing area-under-the-curve measurements.