Efficacy, Safety, and Predictor of Response to Belimumab in a Large Nationwide Cohort Study of Patients with Active Systemic Lupus Erythematosus

Luca Iaccarino¹, Francesca Saccon¹, Alessandro Mathieu², Matteo Piga³, Angela Ceribelli⁴, Carlo Selmi⁵, Paolo Cardinaletti⁶, Armando Gabrielli⁷, Andrea Di Matteo⁸, Rossella De Angelis⁹, Paola Faggioli¹⁰, Antonella Laria¹¹, Micaela Fredi¹², Francesca Regola¹³, Angela Tincani¹², Laura Andreoli¹⁴, Giulia Pazzola¹⁵, Carlo Salvarani¹⁵, Francesco Puppo¹⁶, Ottavia Magnani¹⁶, Marcella Prete¹⁷, Elisa Gremese¹⁸, Maria Gerosa¹⁹, Tania Ubiali²⁰, Enrica Bozzolo²¹, Valentina Canti²¹, Vito Racanelli¹⁷, Fabrizio Conti²², Fulvia Ceccarelli²³, Elena Bartoloni²⁴, Roberto Gerli²⁵, Antonio Lobasso²⁶, Amato de Paulis²⁷, Ginevra De Marchi²⁸, Salvatore De Vita²⁹, Alessandra Bortoluzzi³⁰, Marcello Govoni³⁰, Francesco Benvenuti³¹, Margherita Zen³², Marta Mosca³³, Chiara Tani³⁴, Maurizio Rossini³⁵, Giovanni Orsolini³⁵, Salvatore Scarpato³⁶, Ernico Brunetta³⁷, Aurora Zumbo³⁸, Giacomo Tanti³⁹ and Andrea Doria⁴⁰, ¹Department of Medicine-DIMED, University of Padova, Padova, Italy, ²University of Cagliari, Cagliari, Italy, ³Unit and Chair of Rheumatology, University Hospital of Cagliari, Cagliari, Italy, ⁴Rheumatology and Clinical Immunology, Humanitas Research Hospital, Rozzano (MI), Italy, ⁵Rheumatology and Clinical Immunology Unit, Humanitas Research Hospital, Rozzano (MI), Italy, ⁶University of Ancona, Ancona, Italy, ⁷Univeristy of Ancona, Ancona, Italy, ⁸Polytechnic University of Marche, Rheumatology Clinic, Jesi, Italy, ⁹Polytechnic University of Marche, Rheumatology Clinic, jesi, Italy, ¹⁰Hospital of Legnano, Legnano, Italy, ¹¹Hospital of Magenta, Magenta, Italy, ¹²Rheumatology and Clinical Immunology, Spedali Civili and University of Brescia, Brescia, Italy, ¹³University of Brescia, Brescia, Italy, ¹⁴Department of Clinical and Experimental Sciences, Spedali Civili and University of Brescia, Brescia, Italy, Rheumatology and Clinical Immunology, Spedali Civili and University of Brescia, Brescia, Italy, ¹⁵University of Reggio Emilia, Reggio Emilia, Italy, ¹⁶University of Genova, Genova, Italy, ¹⁷University of Bari, Bari, Italy, ¹⁸Division of Rheumatology, Fondazione Policlinico Universitario A.Gemelli IRCCS, Catholic University of the Sacred Heart, Rome, Italy, ¹⁹Istituto Ortopedico Gaetano Pini, University of Milan, Milano, Italy, ²⁰Istituto Gaetano Pini, University of Milano, Milano, Italy, ²¹Hospital San Raffaele, Milano, Italy, ²²Rheumatology Unit, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy, ²³UO Complessa Reumatologia, Policlinico Umberto I Università Sapienza di Roma, Rome, Italy, ²⁴Rheumatology Unit, University of Perugia, Perugia, Italy, ²⁵Department of Medicine, Rheumatology Unit, University of Perugia, Perugia, Italy, ²⁶University Federico II of Napoli, Napoli, Italy, ²⁷Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy, ²⁸Hospital/University of Udine, Udine, Italy, ²⁹Rheumatology Clinic, Academic Hospital S. M. della Misericordia, Medical Area Department, University of Udine, Italy, Udine, Italy, ³⁰UOC of Rheumatology, University Hospital S. Anna, Cona Ferrara, Italy, ³¹University of Padova, Padova, Italy, ³²Division of Rheumatology, University of Padova, Padova, Italy, ³³Rheumatology Unit, University of Pisa, Pisa, Italy, ³⁴Univeristy of Pisa, Pisa, Italy, ³⁵Rheumatology Unit, University of Verona, Verona, Italy, ³⁶Hospital of Salerno, Salerno, Italy, ³⁷Humanitas Hospital, Milano, Italy, ³⁸Humnaitas Hospital, Milano, Italy, ³⁹Catholic University of the sacred hearth, Roma, Italy, ⁴⁰University and Azienda Ospedaliera of Padova, Padova, Italy

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Effective, Lupus and belimumab

Session Information

Date: Tuesday, October 23, 2018

Title: Systemic Lupus Erythematosus – Clinical Poster III: Treatment

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: To investigate effectiveness, safety, and predictors of response to belimumab in patients with active SLE in clinical practice setting.

Methods: Four hundred and one active SLE patients (ACR criteria) with positive anti-dsDNA antibody and low C3 and/or C4, from 22 Italian Centers, were treated with belimumab (10 mg/kg day 0, 14, 28 and then every 28 days), as add-on therapy. They were 366 (91.27%) females, mean age 43.51±11.20 years; mean disease duration 12.79±8.74 years.

SLEDAI-2K, anti-dsDNA, C3, C4, prednisone daily dose, DAS-28, 24-hours proteinuria, CLASIa (Cutaneous LE Disease Area and Severity Index Activity), PGA, Fatigue (VAS 0-10) were recorded at baseline and every 6 months. SLICC-DI was evaluated 5-years before belimumab initiation, at baseline and every year after belimumab initiation. Response was evaluated according to SLE Responder Index-4 (SRI-4) at 12, 24, 36 and 48 months. Adverse events (AEs) were subdivided in noninfectious or infectious AE, and infusion reactions. AE was defined as severe (SAE) when hospitalization was required and/or death and/or life-threatening manifestations occurred. Statistics were performed by pairs T-test, chi-square test and multiple logistic regression analysis using SPSS package (version 22.0).

Results: Mean follow-up was 21.07±15.34 months (range 3-60). Active manifestations requiring the use of belimumab were articular in 40.82%, mucocutaneous in 21.84%, renal in 14.56%, hematologic in 16.32% and serositis in 6.24% of cases. SRI-4 was achieved by 68.2%, 73.3%, 74.7% and 68.3% of patients at 12, 24, 36 and 48 months, respectively. The improvement in clinical and serological variables during the follow-up are reported in the Table.

We observed a decrease in the mean number of flare during belimumab treatment compared with the corresponding period before belimumab initiation (p<0.0001).

SLEDAI-2K ≥10 resulted as an independent predictor of response by logistic regression at month 12 and 24 (p=0.003 and p=0.025).

Mean SLICC-DI was 0.71±1.07 five years before belimumab initiation, 0.96±1.31 at baseline and 1.00±1.52, 1.09±1,70, 1.27±1.91 at 24, 36 and 48 months of follow-up, respectively. We observed a significant increase in mean SLICC-DI between 5 years before belimumab initiation and baseline (p<0.01), but not between baseline and 2-year follow-up.

A total of 8,831 infusions were analyzed. A total of 681 AEs were observed in 298 patients, SAEs were 32 in 29 patients. No severe infusion reactions were observed; 15 patients had infective SAEs, and 18 non infective SAEs.

Conclusion: Belimumab reduces global and organ specific disease activity, frequency of flares and prednisone daily dosage. SLDAI-2K ≥10 at baseline was the best predictor of response in our cohort of patients with active SLE. Belimumab was well tolerated.

Disclosure: L. Iaccarino, GSK, 5; F. Saccon, None; A. Mathieu, None; M. Piga, None; A. Ceribelli, None; C. Selmi, AbbVie, Janssen, MSD, Novartis, Pfizer, 2,AbbVie, Alfa-Sigma, Biogen, Bristol-Myrs Squibb, Celgene, Eli-Lilly, GlaxoSmithKline, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Roche, Sanofi-Genzyme, UCB, 5, 8; P. Cardinaletti, None; A. Gabrielli, None; A. Di Matteo, None; R. De Angelis, None; P. Faggioli, None; A. Laria, None; M. Fredi, None; F. Regola, None; A. Tincani, Bristol-Myers Squibb, 2,UCB, Inc., 5; L. Andreoli, None; G. Pazzola, None; C. Salvarani, None; F. Puppo, None; O. Magnani, None; M. Prete, None; E. Gremese, AbbVie Inc., 5, 8,Janssen, 5, 8,Lilly, 5, 8,Pfizer, Inc., 5, 8; M. Gerosa, None; T. Ubiali, None; E. Bozzolo, None; V. Canti, None; V. Racanelli, None; F. Conti, None; F. Ceccarelli, None; E. Bartoloni, None; R. Gerli, None; A. Lobasso, None; A. de Paulis, None; G. De Marchi, None; S. De Vita, None; A. Bortoluzzi, None; M. Govoni, None; F. Benvenuti, None; M. Zen, None; M. Mosca, None; C. Tani, None; M. Rossini, None; G. Orsolini, None; S. Scarpato, None; E. Brunetta, None; A. Zumbo, None; G. Tanti, None; A. Doria, AstraZeneca, Baxalta, Bristol-Myers Squibb, Celgene, Eli Lilly, GSK, 5,Bristol-Myers Squibb, GSK, Eli Lilly, 8.

To cite this abstract in AMA style:

Iaccarino L, Saccon F, Mathieu A, Piga M, Ceribelli A, Selmi C, Cardinaletti P, Gabrielli A, Di Matteo A, De Angelis R, Faggioli P, Laria A, Fredi M, Regola F, Tincani A, Andreoli L, Pazzola G, Salvarani C, Puppo F, Magnani O, Prete M, Gremese E, Gerosa M, Ubiali T, Bozzolo E, Canti V, Racanelli V, Conti F, Ceccarelli F, Bartoloni E, Gerli R, Lobasso A, de Paulis A, De Marchi G, De Vita S, Bortoluzzi A, Govoni M, Benvenuti F, Zen M, Mosca M, Tani C, Rossini M, Orsolini G, Scarpato S, Brunetta E, Zumbo A, Tanti G, Doria A. Efficacy, Safety, and Predictor of Response to Belimumab in a Large Nationwide Cohort Study of Patients with Active Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/efficacy-safety-and-predictor-of-response-to-belimumab-in-a-large-nationwide-cohort-study-of-patients-with-active-systemic-lupus-erythematosus/. Accessed .

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