CO:11:6 | Off-therapy remission in systemic lupus erythematosus: the BLys lupus flare index (BLyFI) as a decision tool for immunosuppressive therapy withdrawal in remitted patients

Noemi Merra¹, Anna Giorgia Osele¹, Davide Ragno¹, Greta Hulej¹, Zahrà Rahmé¹, Ilenia Anna Gennaio¹, Filippo Vesentini¹, Margherita Zen¹, Luca Iaccarino¹, Andrea Doria¹ | Università degli Studi di Padova, Italy

Background. The most recent literature regarding the discontinuation of immunosuppressive therapy (IS) in patients with systemic lupus erythematosus (SLE) in remission highlights that approximately one in four patients experience a relapse. We have learned how flare-ups impact the extent of accumulated damage, caused on the one hand by disease activity and on the other by prolonged exposure to IS therapy. This clearly supports the need for a tool that guides clinicians towards safe management of therapy in patients in remission. We therefore evaluated several serological biomarkers, such as anti-native DNA, C3, C4, anti-C1q, anti-PTX3, APRIL, BLyS, C3a and C3c. Based on the results observed, we created an algorithm capable of estimating the risk of relapse in patients in remission following the discontinuation of IS therapy. Materials and methods. We conducted a retrospective study of 57 patients with SLE who had discontinued IS therapy after achieving remission. Clinical SLEDAI-2K = 0, associated with stable background therapy and/or a prednisone dose ≤5 mg/day, identified remission status. Flares were defined according to the SLEDAI-Flare-Index. A multivariate logistic regression model was applied to evaluate the association between the risk of flare and clinical and serological data collected in the 6 months following discontinuation of IS therapy. The variables found to be significant were then combined to create a flare predictor algorithm. Results. Fifteen patients (26.3%) experienced a relapse, on average 4.35 (± 4.1) years after discontinuation of IS therapy. Serum BLyS levels were significantly higher in patients with relapse (median 0.869 ng/mL, IQR 0.669–1.262; p = 0.033) than in patients who remained in remission. Maintenance therapy with hydroxychloroquine (HCQ) at the time of IS therapy discontinuation showed a protective effect (OR = 0.21; p = 0.019). BLyS values, native anti-DNA antibody positivity, remission greater than 3 years at the time of IS therapy discontinuation, and HCQ use, weighted as shown in Figure 1, provided the optimal combination for constructing a flare prediction algorithm (AUC = 0.779; SE = 100%; SP = 62.9%). All patients who experienced a flare-up had a BLys Lupus Flare Index (BLyFI) value greater than the cut-off of -3.43. Conclusions. Through the combination of serum BLyS levels with other variables readily available in clinical practice, we have developed a non-invasive tool capable of predicting the risk of relapse in patients in remission candidates for discontinuation of immunosuppressive therapy.