51成人动漫

Gradual withdrawal of glucocorticoids was successful among patients with systemic lupus erythematosus (SLE) after 2 years of clinically quiescent disease, without an increased likelihood of flares, Canadian researchers reported.

At 12 months, the flare rate among patients who had slowly tapered their glucocorticoid was 17.6% compared with 29.4% among patients who maintained a low prednisone dose of 5 mg/day (P=0.023), according to Murray B. Urowitz, MD, and colleagues from the University of Toronto.

And at 24 months, the flare rates in the withdrawal and maintenance groups were 33.3% versus 50%, respectively (P=0.01), the researchers reported online in

"Glucocorticoids remain the cornerstone of treatment in SLE, not only for the management of active disease but also as maintenance in clinically quiescent patients, albeit in lower doses," they wrote. However, even low doses of these drugs carry significant adverse events and are associated with bone mineral density loss and other damage.

A conducted in France found a significantly lower risk of flare among patients who remained on maintenance prednisone compared with those who had abruptly withdrawn the drug, with a relative risk of 0.2 (95% CI 0.1-0.7).

"At the University of Toronto Lupus Clinic, we follow a different approach on glucocorticoid tapering, which mandates a gradual decrease in the daily prednisone dose over many months," Urowitz and colleagues explained.

This tapering schedule for the withdrawal group was as follows: During the first week, the patients took the usual dose of 5 mg per day for 6 days and a reduced dose of 4 mg for 1 day. In the second week, the usual dose was taken for 5 days and the reduced dose for 2 days. In the third week, the 5-mg dose was taken for 4 days and the reduced dose for 3 days, and so on, remaining at that reduced dose until the next clinic visit, when further tapering began. This permitted discontinuation of prednisone over 9 to 18 months.

To compare the effects of slow withdrawal versus maintenance, the researchers conducted an observational study of patients who had been in clinical remission for at least 2 years, with a SLE Disease Activity Index (SLEDAI) of 0. At the beginning of the study, all patients were receiving 5 mg/day of prednisone along with stable doses of antimalarials and immunosuppressives.

The decision regarding withdrawal or maintenance was made by the individual treating physician. Propensity score matching was performed to account for baseline differences among patients.

Flare was defined as any increase (except minor fluctuations in serology) in the SLEDAI, while moderate-to-severe flares were defined as any increase in SLEDAI requiring treatment escalation or an increase of four points or more on the SLEDAI.

After propensity score matching, each group included 102 patients. The majority were women whose age averaged 42 and whose disease duration was approximately 12 years. Duration of clinical remission was 3.6 years.

At 12 months, there were no differences between the withdrawal and maintenance groups in rates of flare requiring treatment escalation (10.8% vs 13.7%, P=0.467) or in rates of increases in SLEDAI of four or more points (6.9% vs 11.8%, P=0.197).

But at 24 months, rates of flare requiring treatment escalation in the withdrawal and maintenance groups were 14.7 versus 27.5% (P=0.024), while rates of flare involving a four-point increase in SLEDAI were 12.7% versus 26.5% (P=0.013).

The most common manifestations of flare were cutaneous and polyarthritis in both groups, with no difference in organ system involvement between the groups.

Fewer patients in the withdrawal group had developed new disease damage (6.9% vs 17.6%, P=0.022) or glucocorticoid-associated damage (2.9% vs 11.8%, P=0.02) at 24 months.

In a multivariate analysis, no baseline factors were found to be predictive of clinical flares, including age, disease duration, serologic abnormalities, and cumulative prednisone dose prior to study entry.

An additional analysis of 263 patients who had been in remission for less than 2 years found that the flare rate was the same, at 67%, in both withdrawal and maintenance groups at 2 years, "implying that the duration of remission is a critical factor for successful glucocorticoid tapering," the researchers observed.

"In conclusion, gradual withdrawal of prednisone seems safer than abrupt discontinuation in patients with clinically quiescent SLE and could be attempted because the vast majority of these patients will not develop a moderate-to-severe flare within 24 months," they wrote.

A limitation of the study was its observational, rather than randomized, design.

Comment