Disease Flares Common After Discontinuing Immunosuppressants in Systemic Lupus Erythematosus

Systemic lupus erythematosus
Systemic lupus erythematosus
Researchers assessed the flare rate and predictors after immunosuppressant withdrawal in systemic lupus erythematosus remission.

Disease flares are common after the withdrawal of immunosuppressant therapy in patients with systemic lupus erythematosus (SLE), according to research results published in Rheumatology. However, treatment with antimalarial therapies may significantly reduce this risk.

Researchers sought to determine the rate of immunosuppressant discontinuation after the achievement of remission in SLE to identify potential predictors of subsequent disease flares and evaluate the flare-free survival rate. Patient information was collected from the Lupus Database, which included prospective data from patients recruited between 1970 and 2018.

In total, 456 patients (402 women; mean age, 45±13 years; mean disease duration, 17.4±9 years) were included in the follow-up during the study period. Of these, 319 (70%) were treated with immunosuppressants and were eligible in the current study.

Among the study cohort, 47% of patients received immunosuppressants for lupus nephritis, 15.7% for arthritis, 5.3% for hematologic abnormalities, 4.1% for skin rash, 2.2% for skin rash and arthritis, 1.9% for neuroSLE, 1.3% for vasculitis, and 0.6% for serositis. A total of 21.9% had a multisystemic involvement, and 57.7% of patients were treated with more than 1 immunosuppressant throughout the course of their disease.

Immunosuppressant breakdown included 209 patients treated with mycophenolate mofetil (MMF), 136 with azathioprine (AZA), 95 with cyclophosphamide (CYC), 84 with methotrexate (MTX), 65 with cyclosporine (CSA), and 10 with leflunomide (LEF).

Among patients treated with immunosuppressants, immunosuppressant use was discontinued in 43.6%: 43.8% of patients receiving MMF, 25.2% receiving AZA, 15.1% receiving MTX, 9.3% receiving CSA, 4.3% receiving CYC, and 2.1% on LEF. Mean patient age at immunosuppressant discontinuation was 35.4±11.4 years with a mean follow-up duration of 91.4±71.9 months (range, 6-372 months).

Immunosuppressants were discontinued because of remission in 75.5% of patients (n=105); of these, 24.8% experienced a flare after a median follow-up of 57 months (range, 6-264 months). Among patients with either poor adherence or intolerance, 67.7% relapsed (odds ratio [OR], 6.9; 95% CI, 2.94-16.59; P <.001) after a median follow-up of 8 months (range 1-72 months; P =.009).

Among remitted patients, the mean follow-up duration following disease flare was 56.5±52.8 months; the mean time needed to achieve remission was similar in patients who did or did not flare.

Flare proportion and time to flare did not differ by lupus manifestation. Compared with patients in whom other types of immunosuppressants were discontinued, patients in whom treatment with MTX was discontinued were more likely to flare (P =.0026); in addition, these patients also had shorter flare-free survival. Overall, 50% of flare cases were categorized as severe.

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At the time of immunosuppressant discontinuation, 16.2% of patients were in complete remission. Patients in either complete or clinical remission had similar flare-free survival rates. Investigators adjusted for hydroxychloroquine (HCQ) use and found that flare risk was similar in both patient groups (OR, 1.8; 95% CI, 0.419-8.103; P =.4). Flare frequency was significantly lower in patients treated with HCQ compared with patients who were not treated with HCQ (19.0% vs 47.6%; P =.015). The protective effect of HCQ against flare “progressively increased as the duration of remission lengthened.” Mean flare-free survival was longer in patients treated with HCQ (73.4±44.38 months vs 55.6±50.3 months), according to the results of a univariate analysis.

Study limitations included the retrospective analysis of data prospectively collected from a single center, and the relatively low number of patients who discontinued immunosuppressants.

“During treatment tapering and after withdrawal, a close surveillance should be planned, especially in the first months, in order to detect early signs or symptoms of disease relapse,” the researchers concluded. “Patients should be informed that…they must continue to perform routine laboratory tests and regularly attend clinical evaluations.”


Zen M, Saccon F, Gatto M, et al. Prevalence and predictors of flare after immunosuppressant discontinuation in patients with systemic lupus erythematosus in remission [published October 23, 2019]. Rheumatology. doi:10.1093/rheumatology.kez422