In an Italian cohort study, the attempt to stop glucocorticoids in patients with systemic lupus erythematosus (SLE) was successful in the majority of cases
Employees of the University of Pisa, Italy, retrospectively evaluated data that had been collected prospectively in a monocentric cohort study with patients with SLE started in 2012. Data from those patients who had received glucocorticoid therapy at the start of the study and had appeared on at least two study dates between 2012 and 2017 were taken into account. Disease activity was assessed with the "Safety of Estrogens in Lupus Erythematosus National Assessment - Systemic Lupus Erythematosus Disease Activity Index" (SELENA-SLEDAI) and organ damage with the "American College of Rheumatology/Systemic Lupus International Collaborating Clinics Damage Index" (ACR-SLICC/DI). Remission was defined according to the European Consensus Criteria ( Deļ¬nitions of Remission in SLE or DORIS) and low disease activity according to the criteria of the Asian Pacific Lupus Consortium (Lupus Low Disease Activity State or LLDAS).
With 148 patients, the evaluation included almost half of the entire cohort (n=310). The average age was 42.2 years, with a mean age of onset of the disease of about 14 years. With 76.3% of the patients, musculoskeletal manifestations were the most frequent in anamnestic terms. About every second patient had hematological (57.5%), cutaneous (56.2%) and/or renal (53.4%) manifestations.
During the six-year follow-up, 91 (61.5%) of these patients attempted to stop glucocorticosteroids in a gradual manner. At this time, 74.2% of patients took hydroxychloroquine and 37% a traditional immunosuppressant. 4.7% received a biologic. 97% had low disease activity and about 90% were clinically or completely in remission. The median glucocorticoid dose was 5 mg prednisolone equivalent.
In 77 patients (84.6%), glucocorticoid therapy was discontinued after a median of eleven months. In 14 patients (15.4%), however, the dose reduction resulted in a flare-up of symptoms, especially arthralgia and fatigue. Compared to these patients, those for whom glucocorticoid therapy could be stopped tended to be somewhat younger (40.7 vs. 44.6 years; p=0.06). Organ damage was significantly less pronounced (SLICC 0 vs. 1; p=0.033). Disease activity was also significantly lower on average at the beginning of dose reduction (SLEDAI 1.31 vs. 2.57; p=0.01).
In 23% of the patients in whom glucocorticoid therapy was initially stopped, the disease flared up again after a median follow-up of two years. While 27.7% of these patients experienced a severe relapse, 72.2% experienced mild symptoms. However, almost all of these patients (94.4%) needed to resume glucocorticoid therapy. In the median, the symptoms occurred after one year and affected 33.3% of the joints, 22.2% of the kidneys, 16.6% of the blood count and the skin respectively. One patient each (5.5%) had serositis or neurological symptoms. The most important predictor for a recurrence of the symptoms was the time since the last relapse. It was significantly shorter in these patients with two years (1-4 years) than in patients without relapse with four years (2-9 years; p<0.001). A low SLEDAI level was associated with a lower risk of recurrence (p=0.031).
The slow release of glucocorticoids is one of the major therapeutic goals in patients with SLE. In principle, the decision is at the discretion of the physician, as there are hardly any orientations for this strategy. In the literature, data on the proportion of patients in whom this is possible vary considerably. In some cases, they are in the single-digit percentage range. In this study, however, about three-quarters of the patients did not experience a flare-up of symptoms after complete discontinuation of glucocorticoids. The risk of recurrence was significantly influenced by the disease activity at the beginning of dose reduction and the time since the last relapse. The ideal situation for dose reduction is therefore when the patient has low disease activity and the last relapse occurred some time ago. After complete discontinuation, patients must be closely monitored for recurrence of symptoms.
Source:
Tani C, Elefante E, Signorini V et al. Glucocorticoid withdrawal in systemic lupus erythematosus: are remission and low disease activity reliable starting points for stopping treatment? A real-life experience. RMD Open 2019; 5(2): e000916