Of course, observational data are affected by limitations not seen in randomized data. However, it is not possible, logistically or ethically, to maintain randomization in symptomatic patients with RA over periods longer than two years.27 Therefore, accurate knowledge concerning the safety and effectiveness of long-term treatment of RA with prednisone <5 mg/day requires observational data to complement clinical trials, as summarized below:28
The mean initial prednisone dose in 308 patients with RA treated between 1980 and 2004, analyzed in five-year periods, declined from 10.3 mg/day in 1980–1985 to 6.5 mg/day in 1985–1989, 5.1 mg/day in 1990–1994, 4.1 mg/day in 1995–1999, and 3.6 mg/day in 2000–2004 (see Figure 1a, p. 23). The proportion of patients whose initial dose was <5 mg/day increased from zero in 1980–1984 to 4% in 1985–1989, 23% in 1990–1994, 67% in 1995–1999, and 86% in 2000–2004 (see Figure 1b, p. 23). The proportion treated initially with 5 mg/day was 51%, 80%, 70%, 26%, and 10%, in the five-year periods, respectively. The proportion treated initially with >5 mg/day was 49%, 16%, 7%, 7%, and 3%, in the five-year periods, respectively (see Figure 1b, p. 23). Over this period, the proportion of patients treated with methotrexate rose from 10%, to 26%, 57%, 71%, and 78% in the respective five-year periods. (see Figure 1c, p. 23).23
Higher mean initial prednisone doses were administered to patients with greater disease severity. In patients treated with ≥5 mg/day, the mean baseline MDHAQ physical function score was 3.5 (0–10 scale), mean pain score 6.3 (0–10 scale), and mean RAPID3 17.3 (0–30 scale) versus 2.4, 5.2, and 13.2, respectively, in patients treated initially with <5 mg/day.25
Improvement in clinical status over 12 months for MDHAQ function, pain, and RAPID3 was similar in patients with initial dose ≥5 mg/day—40%, 37%, and 38%, respectively—compared to patients with initial dose <5 mg/day, in whom improvement was 34%, 37%, and 37%, respectively.25 Therefore, the 86% of patients treated with <5 mg/day in 2000–2004 experienced benefit similar to those treated with higher doses, albeit that their clinical status was milder.5 These data reflect confounding by indication that patients with more severe disease received higher prednisone dose.
Clinical improvement was maintained for up to eight years in most patients.25 These findings differ considerably from those in the 1980s and 1990s, when initial improvement was followed by progressive declines in clinical status after two to three years in most patients.5,29
