In addition to various immunosuppressive agents, belimumab and anifrolumab became available in Japan. We aimed to investigate glucocorticoid-free clinical remission in a single-centre retrospective cohort in October 2023.
Methods
Our cohort included patients with SLE who needed to start or increase glucocorticoids for disease activity and were followed up for more than 1 year. We investigated the rate of achievement of clinical remission off corticosteroids (CR off C), defined as no clinical score on the SLEDAI-2K without glucocorticoids, baseline predictors of CR off C, medications used when CR off C was achieved, and flare rates following CR off C.
Results
Out of the 60 patients followed for an average of 5.4 (±2.6) years, 17 (28.3%) achieved CR off C in 3.6 (±1.2) years after enrolment. Use of belimumab and anifrolumab accounted for eight (47.1%) of the achievers. Among the baseline data, male sex, recent enrolment, high glucocorticoid dose, and detection of immune complex (IC) significantly predicted CR off C, while lupus nephritis (LN) and a low C3 level tended to predict it. In the multivariate analysis, IC detection was the only predictor of CR off C. Clinical flares were observed in 5.9% of the achievers during a median 1.2 years after achievement of CR off C.
Conclusion
In the era of biologics, CR off C was achieved in 28.3% of the patient cohort requiring the start or increase of glucocorticoids for disease activity, with a relatively low rate of flares, suggesting that glucocorticoid-free clinical remission is an achievable target in SLE. IC disease, represented by male sex or nephritis, is likely to benefit from currently available medications.
JenksSACashmanKSZumaqueroE, et al.Distinct effector B cells induced by unregulated toll-like receptor 7 contribute to pathogenic responses in systemic lupus erythematosus. Immunity2018; 49: 725–739.
2.
JenksSACashmanKSWoodruffMC, et al.Extrafollicular responses in humans and SLE. Immunol Rev2019; 288: 136–148.
3.
FillatreauSManfroiBDörnerT. Toll-like receptor signalling in B cells during systemic lupus erythematosus. Nat Rev Rheumatol2021; 17: 98–108.
4.
MurayamaGChibaAKugaT, et al.Inhibition of mTOR suppresses IFNα production and the STING pathway in monocytes from systemic lupus erythematosus patients. Rheumatology2020; 59: 2992–3002.
5.
RönnblomLLeonardD. Interferon pathway in SLE: one key to unlocking the mystery of the disease. Lupus Sci Med2019; 6(1): e000270.
6.
MorandEFFurieRTanakaY, et al.Trial of anifrolumab in active systemic lupus erythematosus. N Engl J Med2020; 382: 211–221.
7.
FurieRRovinBHHoussiauF, et al.Two-year, randomized, controlled trial of belimumab in lupus nephritis. N Engl J Med2020; 383: 1117–1128.
8.
Ruiz-IrastorzaGOlivaresNRuiz-ArruzaI, et al.Predictors of major infections in systemic lupus erythematosus. Arthritis Res Ther2009; 11: R109.
9.
HidekawaCYoshimiRSaigusaY, et al.Protective effect of hydroxychloroquine on infections in patients with systemic lupus erythematosus: an observational study using the LUNA registry. Front Immunol2023; 14: 1227403.
10.
WiebeEHuscherDSchaumburgD, et al.Optimising both disease control and glucocorticoid dosing is essential for bone protection in patients with rheumatic disease. Ann Rheum Dis2022; 81: 1313–1322.
11.
AdamiGFassioARossiniM, et al.Bone loss in inflammatory rheumatic musculoskeletal disease patients treated with low-dose glucocorticoids and prevention by anti-osteoporosis medications. Arthritis Rheumatol2023; 75: 1762–1769.
12.
GladmanDDUrowitzMBRahmanP, et al.Accrual of organ damage over time in patients with systemic lupus erythematosus. J Rheumatol2003; 30: 1955–1959.
13.
van VollenhovenRFMoscaMBertsiasG, et al.Treat-to-target in systemic lupus erythematosus: recommendations from an international task force. Ann Rheum Dis2014; 73: 958–967.
14.
FanouriakisAKostopoulouMAndersenJ, et al.EULAR recommendations for the management of systemic lupus erythematosus: 2023 update. Ann Rheum Dis2024; 83: 15–29, (in press).
ZenMIaccarinoLGattoM, et al.Prolonged remission in Caucasian patients with SLE: prevalence and outcomes. Ann Rheum Dis2015; 74: 2117–2122.
17.
ZenMIaccarinoLGattoM, et al.The effect of different durations of remission on damage accrual: results from a prospective monocentric cohort of Caucasian patients. Ann Rheum Dis2017; 76: 562–565.
18.
van VollenhovenRVoskuylABertsiasG, et al.A framework for remission in SLE: consensus findings from a large international task force on definitions of remission in SLE (DORIS). Ann Rheum Dis2017; 76: 554–561.
19.
van VollenhovenRFBertsiasGDoriaA, et al.2021 DORIS definition of remission in SLE: final recommendations from an international task force. Lupus Sci Med2021;8:e000538.
20.
HochbergMC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum1997; 40: 1725.
21.
TanEMCohenASFriesJF, et al.The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum1982; 25: 1271–1277.
22.
IsenbergDARahmanAAllenE, et al.BILAG 2004. Development and initial validation of an updated version of the British Isles Lupus Assessment Group's disease activity index for patients with systemic lupus erythematosus. Rheumatology2005; 44: 902–906.
23.
TaniCElefanteESignoriniV, et al.Glucocorticoid withdrawal in systemic lupus erythematosus: are remission and low disease activity reliable starting points for stopping treatment? A real-life experience. RMD Open2019; 5: e000916.
24.
NakaiTFukuiSIkedaY, et al.Glucocorticoid discontinuation in patients with SLE with prior severe organ involvement: a single-center retrospective analysis. Lupus Sci Med2022; 9(1): e000682.
25.
FasanoSCosciaMAPierroL, et al.Which patients with systemic lupus erythematosus in remission can withdraw low dose steroids? Results from a single inception cohort study. Lupus2021; 30: 991–997.
26.
NishiKOguraMIshiwaS, et al.Glucocorticoid discontinuation in pediatric-onset systemic lupus erythematosus: a single-center experience. Pediatr Nephrol2022; 37: 2131–2139.
27.
GinzlerEMWallaceDJMerrillJT, et al.Disease control and safety of belimumab plus standard therapy over 7 years in patients with systemic lupus erythematosus. J Rheumatol2014; 41: 300–309.
28.
MiyazakiYNakayamadaSSonomotoK, et al.Efficacy and safety of belimumab during maintenance therapy in patients with systemic lupus erythematosus. Rheumatology2022; 61: 3614–3626.
29.
NakaiTFukuiSSawadaH, et al.Disease-modifying effect and long-term safety of belimumab in patients with systemic lupus erythematosus: a single-center retrospective study. Lupus2023; 32: 1518–1527, (in press).
30.
CollinsCECortes-HernándezJGarciaMA, et al.Real-world effectiveness of belimumab in the treatment of systemic lupus erythematosus: pooled analysis of multi-country data from the OBSErve studies. Rheumatol Ther2020; 7: 949–965.
31.
HammamNEvansMBellCF, et al.Evaluating the use of glucocorticoids among belimumab-treated patients with systemic lupus erythematosus in real-world settings using the rheumatology informatics system for effectiveness registry. ACR Open Rheumatol2022; 4: 883–889.
32.
ZenMGattoMDepascaleR, et al.Early and late response and glucocorticoid-sparing effect of belimumab in patients with systemic lupus erythematosus with joint and skin manifestations: results from the belimumab in real life setting study-joint and skin (BeRLiSS-JS). J Pers Med2023; 13: 691.
33.
NikoloudakiMNikolopoulosDKoutsovitiS, et al.Clinical response trajectories and drug persistence in systemic lupus erythematosus patients on belimumab treatment: a real-life, multicentre observational study. Front Immunol2023; 13: 1074044.
34.
KalunianKCFurieRMorandEF, et al.A randomized, placebo-controlled phase III extension trial of the long-term safety and tolerability of anifrolumab in active systemic lupus erythematosus. Arthritis Rheumatol2023; 75: 253–265.
35.
VitalEMMerrillJTMorandEF, et al.Anifrolumab efficacy and safety by type I interferon gene signature and clinical subgroups in patients with SLE: post hoc analysis of pooled data from two phase III trials. Ann Rheum Dis2022; 81: 951–961.
36.
ShirahamaYHashimotoAOnoN, et al.Relationships between Type 1 interferon signatures and clinical features of the new-onset lupus patients in Japan. Mod Rheumatol2024; 34: 346–351, (in press).
37.
AndradeRMAlarcónGSFernándezM, et al.Accelerated damage accrual among men with systemic lupus erythematosus: XLIV. Results from a multiethnic US cohort. Arthritis Rheum2007; 56: 622–630.
38.
NusbaumJSMirzaIShumJ, et al.Sex differences in systemic lupus erythematosus: epidemiology, clinical considerations, and disease pathogenesis. Mayo Clin Proc2020; 95: 384–394.
39.
YoshidaHMusoEInoueS, et al.Evaluation of circulating immune complexes in lupus nephritis by solid phase C1q and conglutinin binding assays. Nihon Jinzo Gakkai Shi1984; 26: 293–300.
40.
MusoEYoshidaHSekitaK, et al.Immunopathological correlations of circulating immune complexes and anti-DNA antibodies to glomerular lesions in systemic lupus erythematosus. Nihon Jinzo Gakkai Shi1987; 29: 501–509.
41.
YamatoMShiraiTIshiiY, et al.Impact of subcutaneous belimumab on disease activity, patient satisfaction, and metabolic profile in long-lasting systemic lupus erythematosus. Clin Rheumatol2024; 43: 1023–1035, (in press).
42.
SohrabianAParodisICarlströmer-BerthénN, et al.Increased levels of anti-dsDNA antibodies in immune complexes before treatment with belimumab associate with clinical response in patients with systemic lupus erythematosus. Arthritis Res Ther2019; 21: 259.
43.
GoswamiRPSitHGhoshP, et al.Steroid-free remission in lupus: myth or reality; an observational study from a tertiary referral centre. Clin Rheumatol2019; 38: 1089–1097.
44.
JiLXieWFasanoS, et al.Risk factors of flare in patients with systemic lupus erythematosus after glucocorticoids withdrawal. A systematic review and meta-analysis. Lupus Sci Med2022; 9(1): e000603.
45.
ZhangFBaeSCBassD, et al.A pivotal phase III, randomised, placebo-controlled study of belimumab in patients with systemic lupus erythematosus located in China, Japan and South Korea. Ann Rheum Dis2018; 77: 355–363.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
