Early Disease and Low Baseline Damage as Predictors of Response to Belimumab in Patients With Systemic Lupus Erythematosus in a Real-Life Setting

被引：90

作者：

Gatto, Mariele ^{[1
]}

Saccon, Francesca ^{[1
]}

Zen, Margherita ^{[1
]}

Regola, Francesca ^{[2
]}

Fredi, Micaela ^{[2
]}

Andreoli, Laura ^{[2
]}

Tincani, Angela ^{[2
]}

Urban, Maria Letizia ^{[3
]}

Emmi, Giacomo ^{[3
]}

Ceccarelli, Fulvia ^{[4
]}

Conti, Fabrizio ^{[4
]}

Bortoluzzi, Alessandra ^{[5
,6
]}

Govoni, Marcello ^{[5
,6
]}

Tani, Chiara ^{[7
]}

Mosca, Marta ^{[7
]}

Ubiali, Tania ^{[8
]}

Gerosa, Maria ^{[8
]}

Bozzolo, Enrica ^{[9
]}

Canti, Valentina ^{[9
]}

Cardinaletti, Paolo ^{[10
]}

Gabrielli, Armando ^{[10
]}

Tanti, Giacomo ^{[11
]}

Gremese, Elisa ^{[11
,12
]}

De Marchi, Ginevra ^{[13
]}

De Vita, Salvatore ^{[13
]}

Fasano, Serena ^{[14
]}

Ciccia, Francesco ^{[14
]}

Pazzola, Giulia ^{[15
]}

Salvarani, Carlo ^{[15
,16
]}

Negrini, Simone ^{[17
]}

Puppo, Francesco ^{[17
]}

Di Matteo, Andrea ^{[10
]}

De Angelis, Rossella ^{[10
]}

Orsolini, Giovanni ^{[18
]}

Rossini, Maurizio ^{[18
]}

Faggioli, Paola ^{[19
]}

Laria, Antonella ^{[19
]}

Piga, Matteo ^{[20
,21
]}

Mathieu, Alessandro ^{[20
,21
]}

Scarpato, Salvatore ^{[22
]}

Rossi, Francesca W. ^{[23
]}

de Paulis, Amato ^{[23
]}

Brunetta, Enrico ^{[24
,25
]}

Ceribelli, Angela ^{[26
]}

Selmi, Carlo ^{[25
,27
]}

Prete, Marcella ^{[28
]}

Racanelli, Vito ^{[28
]}

Vacca, Angelo ^{[28
]}

Bartoloni, Elena ^{[29
]}

Gerli, Roberto ^{[29
]}

机构：

[1] Univ Padua, Padua, Italy

[2] ASST Spedali Civili Brescia, Brescia, Italy

[3] Univ Florence, Florence, Italy

[4] Sapienza Univ, Rome, Italy

[5] Univ Ferrara, Ferrara, Italy

[6] Azienda Osped Univ Ferrara, Ferrara, Italy

[7] Univ Pisa, Pisa, Italy

[8] ASST Gaetano Pini, Milan, Italy

[9] IRCCS Osped San Raffaele, Milan, Italy

[10] Univ Politecn Marche, Ancona, Italy

[11] Univ Cattolica Sacro Cuore, Sede Roma, Rome, Italy

[12] Fdn Policlin Univ A Gemelli, IRCCS, Rome, Italy

[13] Univ Udine, Udine, Italy

[14] Univ Campania Luigi Vanvitelli, Naples, Italy

[15] Azienda Unita Sanit Locale Reggio Emilia, IRCCS, Reggio Emilia, Italy

[16] Univ Modena & Reggio Emilia, Reggio Emilia, Italy

[17] Univ Genoa, Genoa, Italy

[18] Univ Verona, Verona, Italy

[19] ASST Ovest Milanese, Milan, Italy

[20] Azienda Osped Univ Cagliari Univ Clin, Cagliari, Italy

[21] Univ Cagliari, Cagliari, Italy

[22] Osped M Scarlato, Scafati, Italy

[23] Univ Napoli Federico II, Naples, Italy

[24] Humanitas Res Hosp, Milan, Italy

[25] Univ Milan, Milan, Italy

[26] IRCCS Ist Clin Humanitas, Reumatol Immunol Clin, Milan, Italy

[27] IRCCS Ist Clin Humanitas, Reumatol & Immunol Clin, Milan, Italy

[28] Univ Bari, Bari, Italy

[29] Univ Perugia, Perugia, Italy

来源：

ARTHRITIS & RHEUMATOLOGY | 2020年 / 72卷 / 08期

关键词：

INITIAL VALIDATION; CAUCASIAN PATIENTS; EUROPEAN LEAGUE; ACTIVITY STATE; ORGAN DAMAGE; REMISSION; INDEX; SLE; RECOMMENDATIONS; CLASSIFICATION;

D O I：

10.1002/art.41253

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective To investigate predictors of response, remission, low disease activity, damage, and drug discontinuation in patients with systemic lupus erythematosus (SLE) who were treated with belimumab. Methods In this retrospective study of a multicenter cohort ofSLEpatients who received intravenous belimumab, the proportion of patients who achieved remission, low disease activity, and treatment response according to theSLEResponder Index 4 (SRI-4) was determined, and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) was used to score disease damage yearly over the follow-up. Predictors of outcomes were analyzed by multivariate logistic regression with the results expressed as odds ratios (ORs) and 95% confidence intervals (95%CIs). Results The study included 466 patients with activeSLEfrom 24 Italian centers, with a median follow-up period of 18 months (range 1-60 months). AnSRI-4 response was achieved by 49.2%, 61.3%, 69.7%, 69.6%, and 66.7% of patients at 6, 12, 24, 36, and 48 months, respectively. Baseline predictors of response at 6 months included a score of >= 10 on theSLEDisease Activity Index 2000 (SLEDAI-2K) (OR3.14 [95%CI2.033-4.860]) and a disease duration of <= 2 years (OR1.94 [95%CI1.078-3.473). Baseline predictors of response at 12 months included a score of >= 10 on theSLEDAI-2K (OR3.48 [95%CI2.004-6.025]) and anSDIscore of 0 (OR1.74 [95%CI1.036-2.923]). Baseline predictors of response at 24 months included a score of >= 10 on theSLEDAI-2K (OR4.25 [95%CI2.018-8.940]) and a disease duration of <= 2 years (OR3.79 [95%CI1.039-13.52]). Baseline predictors of response at 36 months included a score of >= 10 on theSLEDAI-2K (OR14.59 [95%CI3.54-59.79) and baseline status of current smoker (OR0.19 [95%CI0.039-0.69]). Patients who were in remission for >= 25% of the follow-up period (44.3%) or who had low disease activity for >= 50% of the follow-up period (66.1%) accrued significantly less damage (P= 0.046 andP= 0.007). A baselineSDIscore of 0 was an independent predictor of achieving low disease activity in >= 50% of the follow-up period and remission in >= 25% of the follow-up period. Our findings suggest that the lower the baseline damage, the greater the probability of achieving remission over the course of >= 25% of the follow-up. Further, there was a negative association between the number of flares reported prior to belimumab initiation and the frequency of belimumab discontinuation due to inefficacy (P= 0.009). Conclusion In patients with activeSLEand low damage at baseline, treatment with belimumab early in the disease may lead to favorable outcomes in a real-life setting.

引用

页码：1314 / 1324

页数：11

共 35 条

[1] The CLASI (Cutaneous Lupus Erythematosus Disease Area and Severity Index): An outcome instrument for cutaneous lupus erythematosus [J].

Albrecht, J ;

Taylor, L ;

Berlin, JA ;

Dulay, S ;

Ang, G ;

Fakharzadeh, S ;

Kantor, J ;

Kim, E ;

Militello, G ;

McGinnis, K ;

Richardson, S ;

Treat, J ;

Vittorio, C ;

Van Voorhees, A ;

Werth, VP .

JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2005, 125 (05) :889-894

[2]

Anjo C, 2019, SCAND J RHEUMATOL, V2, P1

[3] Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis [J].

Bertsias, George K. ;

Tektonidou, Maria ;

Amoura, Zahir ;

Aringer, Martin ;

Bajema, Ingeborg ;

Berden, Jo H. M. ;

Boletis, John ;

Cervera, Ricard ;

Doerner, Thomas ;

Doria, Andrea ;

Ferrario, Franco ;

Floege, Juergen ;

Houssiau, Frederic A. ;

Ioannidis, John P. A. ;

Isenberg, David A. ;

Kallenberg, Cees G. M. ;

Lightstone, Liz ;

Marks, Stephen D. ;

Martini, Alberto ;

Moroni, Gabriela ;

Neumann, Irmgard ;

Praga, Manuel ;

Schneider, Matthias ;

Starra, Argyre ;

Tesar, Vladimir ;

Vasconcelos, Carlos ;

van Vollenhoven, Ronald F. ;

Zakharova, Helena ;

Haubitz, Marion ;

Gordon, Caroline ;

Jayne, David ;

Boumpas, Dimitrios T. .

ANNALS OF THE RHEUMATIC DISEASES, 2012, 71 (11) :1771-1782

[4] Long-term organ damage accrual and safety in patients with SLE treated with belimumab plus standard of care [J].

Bruce, I. N. ;

Urowitz, M. ;

van Vollenhoven, R. ;

Aranow, C. ;

Fettiplace, J. ;

Oldham, M. ;

Wilson, B. ;

Molta, C. ;

Roth, D. ;

Gordon, D. .

LUPUS, 2016, 25 (07) :699-709

[5] 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus [J].

Fanouriakis, Antonis ;

Kostopoulou, Myrto ;

Alunno, Alessia ;

Aringer, Martin ;

Bajema, Ingeborg ;

Boletis, John N. ;

Cervera, Ricard ;

Doria, Andrea ;

Gordon, Caroline ;

Govoni, Marcello ;

Houssiau, Frederic ;

Jayne, David ;

Kouloumas, Marios ;

Kuhn, Annegret ;

Larsen, Janni L. ;

Lerstrom, Kirsten ;

Moroni, Gabriella ;

Mosca, Marta ;

Schneider, Matthias ;

Smolen, Josef S. ;

Svenungsson, Elisabet ;

Tesar, Vladimir ;

Tincani, Angela ;

Troldborg, Anne ;

van Vollenhoven, Ronald ;

Wenzel, Joerg ;

Bertsias, George ;

Boumpas, Dimitrios T. .

ANNALS OF THE RHEUMATIC DISEASES, 2019, 78 (06) :736-745

[6] Definition and initial validation of a Lupus Low Disease Activity State (LLDAS) [J].

Franklyn, Kate ;

Lau, Chak Sing ;

Navarra, Sandra V. ;

Louthrenoo, Worawit ;

Lateef, Aisha ;

Hamijoyo, Laniyati ;

Wahono, C. Singgih ;

Chen, Shun Le ;

Jin, Ou ;

Morton, Susan ;

Hoi, Alberta ;

Huq, Molla ;

Nikpour, Mandana ;

Morand, Eric F. .

ANNALS OF THE RHEUMATIC DISEASES, 2016, 75 (09) :1615-1621

[7] Novel Evidence-Based Systemic Lupus Erythematosus Responder Index [J].

Furie, Richard A. ;

Petri, Michelle A. ;

Wallace, Daniel J. ;

Ginzler, Ellen M. ;

Merrill, Joan T. ;

Stohl, William ;

Chatham, W. Winn ;

Strand, Vibeke ;

Weinstein, Arthur ;

Chevrier, Marc R. ;

Zhong, Z. John ;

Freimuth, William W. .

ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH, 2009, 61 (09) :1143-1151

[8] New therapeutic strategies in systemic lupus erythematosus management [J].

Gatto, Mariele ;

Zen, Margherita ;

Iaccarino, Luca ;

Doria, Andrea .

NATURE REVIEWS RHEUMATOLOGY, 2019, 15 (01) :30-48

[9] The development and initial validation of the systemic lupus international collaborating clinics American College of Rheumatology Damage Index for Systemic Lupus Erythematosus [J].

Gladman, D ;

Ginzler, E ;

Goldsmith, C ;

Fortin, P ;

Liang, M ;

Urowitz, M ;

Bacon, P ;

Bombardieri, S ;

Hanly, J ;

Hay, E ;

Isenberg, D ;

Jones, J ;

Kalunian, K ;

Maddison, P ;

Nived, O ;

Petri, M ;

Richter, M ;

SanchezGuerrero, J ;

Snaith, M ;

Sturfelt, G ;

Symmons, D ;

Zoma, A .

ARTHRITIS AND RHEUMATISM, 1996, 39 (03) :363-369

[10]

Gladman DD, 2002, J RHEUMATOL, V29, P288

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