Adding Low-Dose Prednisolone Slows Early RA Progression

Low doses of prednisolone given for 2 years along with disease-modifying antirheumatic drug therapy substantially and safely reduced radiographic progression of rheumatoid arthritis in patients with early, active disease, according to the results of two new randomized studies.

Investigators of the two studies say that their findings support the use of low-dose daily prednisolone as a low-risk adjunct to DMARDs in patients with early RA.

One study compared the addition of 7.5 mg/day prednisolone to initial DMARD therapy (either methotrexate or sulfasalazine) with DMARD therapy alone in 250 patients recruited in six centers throughout Sweden from 1995 to 1999. The patients had had RA for 1 year or less.

Patients in the second study were randomized to receive placebo or an even smaller dose of prednisolone—5 mg/day—in addition to therapy with either gold sodium thiomalate or methotrexate.

The 103 patients who completed this study had a slightly longer disease duration—2 years or less—when they started treatment.

They were enrolled in the study between 1993 and 1995 in 20 clinics and private practices in Germany, Austria, and Switzerland.

The two studies were similar in that the choice of DMARD therapy was left to the treating physician. There were no significant differences, however, in the types and dosages of DMARD therapy between the patients who were randomized to receive prednisolone and those who received placebo or no prednisolone.

Concomitant treatment with NSAIDs and osteoporosis prophylaxis with calcium was allowed in both studies, and patients with any history of treatment with DMARDs or glucocorticoids were excluded. Joint destruction was monitored in both studies primarily through radiographs of the hands and feet.

The Swedish investigators used the Sharp score as modified by van der Heijde to assess radiographs at baseline and after 1 and 2 years of treatment. The change in the total score, they found, was significantly lower after 1 and 2 years in the prednisolone group than in the no-prednisolone group. (At 2 years, for instance, the median interquartile change in total score was 1.8 and 3.5, respectively.)

The erosion score also changed significantly less in the prednisolone group, and joint space narrowing was retarded, though to a lesser extent than erosion.

Patients in the prednisolone group also had significantly fewer newly eroded joints after 2 years, as well as improved physical functioning and significantly higher rates of disease remission (51% vs. 39% in the no-prednisolone group at 1 year, and 56% vs. 33% at 2 years), reported Björn Svensson, M.D., Ph.D., of the University of Lund (Sweden), and his associates (Arthritis Rheum. 2005:52;3360–70).

Investigators in the multicountry study used two scoring systems—the Ratingen score and the modified Sharp/van der Heijde score—to assess radiographs taken at 6 months, 1 year, and 2 years after the start of treatment.

Their results were similar: Increases in the Ratingen score, the Sharp score for erosion, and the total Sharp score were significantly less at each point in time in patients taking prednisolone than in patients taking placebo. Changes in the score for joint space narrowing were significantly different only at 6 months.

In addition, clinical and functional outcomes, as well as rates of disease remission, tended to be better—though not to the level of statistical significance—in the prednisolone group, reported Siegfried Wassenberg, M.D., of Evangelisches Fachkrankenhaus Ratingen (Germany), and his associates (Arthritis Rheum. 2005:52;3371–80).

Some side effects such as weight gain (four patients), hypertension (six), Cushing's syndrome (five), and glaucoma (three) were reported only among patients taking prednisolone.

In the Swedish study, the frequency of adverse events was small, investigators said. And in both studies, prednisolone had little or no impact on bone loss.

“It remains to be seen whether dosages lower than 5 mg provide the same benefit with even fewer side effects and whether the same effect can be produced in patients with more advanced disease,” Dr. Wassenberg and associates said.

Low doses of prednisolone given for 2 years along with disease-modifying antirheumatic drug therapy substantially and safely reduced radiographic progression of rheumatoid arthritis in patients with early, active disease, according to the results of two new randomized studies.

Investigators of the two studies say that their findings support the use of low-dose daily prednisolone as a low-risk adjunct to DMARDs in patients with early RA.

One study compared the addition of 7.5 mg/day prednisolone to initial DMARD therapy (either methotrexate or sulfasalazine) with DMARD therapy alone in 250 patients recruited in six centers throughout Sweden from 1995 to 1999. The patients had had RA for 1 year or less.

Patients in the second study were randomized to receive placebo or an even smaller dose of prednisolone—5 mg/day—in addition to therapy with either gold sodium thiomalate or methotrexate.

The 103 patients who completed this study had a slightly longer disease duration—2 years or less—when they started treatment.

They were enrolled in the study between 1993 and 1995 in 20 clinics and private practices in Germany, Austria, and Switzerland.

The two studies were similar in that the choice of DMARD therapy was left to the treating physician. There were no significant differences, however, in the types and dosages of DMARD therapy between the patients who were randomized to receive prednisolone and those who received placebo or no prednisolone.

Concomitant treatment with NSAIDs and osteoporosis prophylaxis with calcium was allowed in both studies, and patients with any history of treatment with DMARDs or glucocorticoids were excluded. Joint destruction was monitored in both studies primarily through radiographs of the hands and feet.

The Swedish investigators used the Sharp score as modified by van der Heijde to assess radiographs at baseline and after 1 and 2 years of treatment. The change in the total score, they found, was significantly lower after 1 and 2 years in the prednisolone group than in the no-prednisolone group. (At 2 years, for instance, the median interquartile change in total score was 1.8 and 3.5, respectively.)

The erosion score also changed significantly less in the prednisolone group, and joint space narrowing was retarded, though to a lesser extent than erosion.

Patients in the prednisolone group also had significantly fewer newly eroded joints after 2 years, as well as improved physical functioning and significantly higher rates of disease remission (51% vs. 39% in the no-prednisolone group at 1 year, and 56% vs. 33% at 2 years), reported Björn Svensson, M.D., Ph.D., of the University of Lund (Sweden), and his associates (Arthritis Rheum. 2005:52;3360–70).

Investigators in the multicountry study used two scoring systems—the Ratingen score and the modified Sharp/van der Heijde score—to assess radiographs taken at 6 months, 1 year, and 2 years after the start of treatment.

Their results were similar: Increases in the Ratingen score, the Sharp score for erosion, and the total Sharp score were significantly less at each point in time in patients taking prednisolone than in patients taking placebo. Changes in the score for joint space narrowing were significantly different only at 6 months.

In addition, clinical and functional outcomes, as well as rates of disease remission, tended to be better—though not to the level of statistical significance—in the prednisolone group, reported Siegfried Wassenberg, M.D., of Evangelisches Fachkrankenhaus Ratingen (Germany), and his associates (Arthritis Rheum. 2005:52;3371–80).

Some side effects such as weight gain (four patients), hypertension (six), Cushing's syndrome (five), and glaucoma (three) were reported only among patients taking prednisolone.

In the Swedish study, the frequency of adverse events was small, investigators said. And in both studies, prednisolone had little or no impact on bone loss.

“It remains to be seen whether dosages lower than 5 mg provide the same benefit with even fewer side effects and whether the same effect can be produced in patients with more advanced disease,” Dr. Wassenberg and associates said.

Low doses of prednisolone given for 2 years along with disease-modifying antirheumatic drug therapy substantially and safely reduced radiographic progression of rheumatoid arthritis in patients with early, active disease, according to the results of two new randomized studies.

Investigators of the two studies say that their findings support the use of low-dose daily prednisolone as a low-risk adjunct to DMARDs in patients with early RA.

One study compared the addition of 7.5 mg/day prednisolone to initial DMARD therapy (either methotrexate or sulfasalazine) with DMARD therapy alone in 250 patients recruited in six centers throughout Sweden from 1995 to 1999. The patients had had RA for 1 year or less.

Patients in the second study were randomized to receive placebo or an even smaller dose of prednisolone—5 mg/day—in addition to therapy with either gold sodium thiomalate or methotrexate.

The 103 patients who completed this study had a slightly longer disease duration—2 years or less—when they started treatment.

They were enrolled in the study between 1993 and 1995 in 20 clinics and private practices in Germany, Austria, and Switzerland.

The two studies were similar in that the choice of DMARD therapy was left to the treating physician. There were no significant differences, however, in the types and dosages of DMARD therapy between the patients who were randomized to receive prednisolone and those who received placebo or no prednisolone.

Concomitant treatment with NSAIDs and osteoporosis prophylaxis with calcium was allowed in both studies, and patients with any history of treatment with DMARDs or glucocorticoids were excluded. Joint destruction was monitored in both studies primarily through radiographs of the hands and feet.

The Swedish investigators used the Sharp score as modified by van der Heijde to assess radiographs at baseline and after 1 and 2 years of treatment. The change in the total score, they found, was significantly lower after 1 and 2 years in the prednisolone group than in the no-prednisolone group. (At 2 years, for instance, the median interquartile change in total score was 1.8 and 3.5, respectively.)

The erosion score also changed significantly less in the prednisolone group, and joint space narrowing was retarded, though to a lesser extent than erosion.

Patients in the prednisolone group also had significantly fewer newly eroded joints after 2 years, as well as improved physical functioning and significantly higher rates of disease remission (51% vs. 39% in the no-prednisolone group at 1 year, and 56% vs. 33% at 2 years), reported Björn Svensson, M.D., Ph.D., of the University of Lund (Sweden), and his associates (Arthritis Rheum. 2005:52;3360–70).

Investigators in the multicountry study used two scoring systems—the Ratingen score and the modified Sharp/van der Heijde score—to assess radiographs taken at 6 months, 1 year, and 2 years after the start of treatment.

Their results were similar: Increases in the Ratingen score, the Sharp score for erosion, and the total Sharp score were significantly less at each point in time in patients taking prednisolone than in patients taking placebo. Changes in the score for joint space narrowing were significantly different only at 6 months.

In addition, clinical and functional outcomes, as well as rates of disease remission, tended to be better—though not to the level of statistical significance—in the prednisolone group, reported Siegfried Wassenberg, M.D., of Evangelisches Fachkrankenhaus Ratingen (Germany), and his associates (Arthritis Rheum. 2005:52;3371–80).

Some side effects such as weight gain (four patients), hypertension (six), Cushing's syndrome (five), and glaucoma (three) were reported only among patients taking prednisolone.

In the Swedish study, the frequency of adverse events was small, investigators said. And in both studies, prednisolone had little or no impact on bone loss.

“It remains to be seen whether dosages lower than 5 mg provide the same benefit with even fewer side effects and whether the same effect can be produced in patients with more advanced disease,” Dr. Wassenberg and associates said.