Background/Purpose:  Belimumab is a biologic drug approved to treat Systemic Lupus Erythematosus (SLE). The efficacy of belimumab has been demonstrated in phase III clinical trials. Here, we provide results from real-life experiences in three Swedish clinical practice settings, with focus on predictors of treatment response. As smoking is coupled with unfavourable prognosis and treatment outcomes, we particularly looked at the effects of smoking on treatment response to belimumab.

Methods:  Fifty-eight patients from Karolinska (n=30), Skåne (n=19), and Linköping (n=9) University Hospitals treated with belimumab were enrolled and followed longitudinally. Global disease activity was assessed using the SLE Disease Activity Index 2000 (SLEDAI-2K), British Isles Lupus Assessment Group (BILAG) index, and a 100 mm Visual Analogue Scale (VAS) for Physician’s Global Assessment (PGA). Organ damage was evaluated using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Response to treatment was defined in line with the SLE responder index (SRI) as a reduction of ≥4 points in SLEDAI-2K, no new BILAG A or ≤1 new BILAG B, and no deterioration in PGA by ≥30 mm. B lymphocyte stimulator (BLyS) levels were determined by ELISA (R&D Systems).

Results:  SLEDAI-2K decreased over time (median baseline score: 8.0; IQR: 4.0–13.8; p<0.0001), corresponding to a decrease of 3.9 over one year and 5.5 over three years. PGA decreased also (p<0.0001), corresponding to a decrease of 28.2 over one year and 39.7 over three years. We also observed decreasing prednisone equivalent dosages (p<0.0001), corresponding to a decrease of 6.3 mg/day over one year and 8.9 mg/day over three years (median baseline dose: 10.0 mg/day; IQR: 7.5–15.0). SDI scores remained stable (p=0.16). We found that a baseline SLEDAI-2K score ≥10 yielded a 2.5-fold increase in the probability of SRI response (HR: 2.553; 95% CI 1.339–4.896; B: 0.937; p=0.004). Baseline prednisone equivalent dosages also predicted SRI response (HR: 1.029; 95% CI 1.003–1.056; B: 0.029; p=0.029). An SDI score >1 at baseline yielded a >2-fold decrease of the probability to attain SRI response (HR: 0.449; 95% CI: 0.208–0.967; B: -0.801; p=0.041). After adjustment for baseline SLEDAI-2K scores and prednisone equivalent dosages, ever smokers had a decreased probability to attain SRI response compared with never smokers (HR: 0.460; 95% CI: 0.223–0.951; B: -0.776; p=0.036), and current smokers showed also a lower probability to attain SRI response compared with non-current smokers (HR: 0.103; 95% CI: 0.025–0.427; B: -2.276; p=0.002). Moreover, higher baseline BLyS levels predicted SRI response after adjustment for the same items (HR: 1.609; 95% CI: 1.149–2.252; B: 0.475; p=0.006).

Conclusion:  In this real-life observational study, disease activity and corticosteroid usage decreased while damage remained stable during treatment with belimumab. Higher baseline SLEDAI-2K scores, corticosteroid dosages and BLyS levels predicted treatment response, whereas smoking and established damage at baseline predicted failure to belimumab treatment. Our results might contribute to a better selection of patients who are likely to respond to belimumab treatment.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/high-baseline-b-lymphocyte-stimulator-blys-levels-predict-response-while-smoking-and-organ-damage-at-baseline-predict-failure-to-belimumab-in-three-swedish-clinical-practice-settings/