Introduction: Children with systemic lupus erythematosus have a more challenging and difficult course as compared to their adult counterparts. Today, the aim of therapy for any child with lupus is to keep the child in a state of sustained remission with minimal or no use of steroids. This laudable goal is often difficult to achieve for the child with lupus. In addition to the use of disease modifying agents, sometimes in combination, Rituximab (RTX) is also used as an off-label indication to manage such patients.
Objectives: To study the use, efficacy and safety of RTX in a cohort of patients with pediatric lupus followed at a single tertiary level center in Northern India.
Methods: This paper is a retrospective review looking at the use of RTX in children with systemic lupus at a tertiary level pediatric rheumatology center in North India over a period of seventeen years. This paper describes the indications, use, efficacy and safety of RTX in childhood systemic lupus erythematosus.
Results: RTX was used in 17 of 225 pediatric lupus patients (7.5%), with the most common indication being resistant renal disease (53%). Significant improvement was seen in all domains studied: The mean SLEDAI was 16.25 prior to RTX and reduced to 1.43 six months after the RTX (p value 0.001), steroid use dropped from 100% pre- RTX to 33% at 2 years, there was a sustained reduction in proteinuria in the patients with nephritis from a mean urine spot protein creatinine ratio of 3.1 pre RTX to 0.4 at one year post RTX (p= .006). Finally, 82% of the children had no flare during the follow up (median 24 months). No patient had any adverse event.
Conclusions: This study confirms that RTX is very effective in childhood lupus and can be safely used even in a country with a very high burden of infectious diseases. This data adds to the scarce literature in this area from the developing world.
SousaSGonçalvesMJInêsLS, et al. Clinical features and long-term outcomes of systemic lupus erythematosus: comparative data of childhood, adult and late-onset disease in a national register. Rheumatol Int2016; 36: 955–960.
2.
BrunnerHIGladmanDDIbañezDUrowitzMDSilvermanED.Difference in disease features between childhood-onset and adult-onset systemic lupus erythematosus. Arthritis Rheum2008; 58: 556–562.
3.
AmbroseNMorganTAGallowayJIonnoauYBeresfordMWIsenbergDA.Differences in disease phenotype and severity in SLE across age groups. Lupus2016; 25: 1542–1550.
4.
Rodriguez-SmithJBrunnerHI.Update on the treatment and outcome of systemic lupus erythematous in children. Curr Opin Rheumatol2019; 31: 464–470.
5.
DaleRCBrilotFDuffyLV, et al. Utility and safety of rituximab in pediatric autoimmune and inflammatory CNS disease. Neurology2014; 83: 142–150.
6.
PetriMOrbaiAMAlarcónGS, et al. Derivation and validation of the systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum2012; 64: 2677–2686.
WeeningJJD’AgatiVDSchwartzMM, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol2004; 15: 241–250.
9.
BertsiasGKTektonidouMAmouraZ, et al. 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. Ann Rheum Dis2012; 71: 1771–1782.
10.
MerrillJTNeuweltCMWallaceDJ, et al. Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus: the randomized, double-blind, phase II/III systemic lupus erythematosus evaluation of rituximab trial. Arthritis Rheum2010; 62: 222–233.
11.
RovinBHFurieRLatinisK, et al. Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the lupus nephritis assessment with rituximab study. Arthritis Rheum2012; 64: 1215–1226.
12.
HugginsJLBrunnerHI.Targeting B cells in the treatment of childhood-onset systemic lupus erythematosus. J Pediatr2006; 148: 571–573.
13.
WillemsMHaddadENiaudetP, et al. Rituximab therapy for childhood-onset systemic lupus erythematosus. J Pediatr2006; 148: 623–627.
PodolskayaAStadermannMPilkingtonCMarksSDTullusK.B cell depletion therapy for 19 patients with refractory systemic lupus erythematosus. Arch Dis Child2008; 93: 401–406.
16.
JanssonAFSenglerCKuemmerle-DeschnerJ, et al. B cell depletion for autoimmune diseases in paediatric patients. Clin Rheumatol2011; 30: 87–97.
17.
SuGXWuFQWangF, et al. Rituximab therapy for severe pediatric systemic lupus erythematosus. Zhonghua Er Ke Za Zhi2012; 50: 697–704.
18.
AlekseevaEDenisovaRValievaS, et al. SAT0458 rituximab in the treatment of children with systemic lupus erythematosus: Analysis of 12 patients. Ann Rheum Dis2013; 72: A736-A.
19.
Pavón-SánchezJMSánchez-SánchezLM.Rituximab in pediatric patients with systemic lupus erythematosus. Gac Med Mex2013; 149: 492–496.
20.
TrachanaMKoutsonikoliAFarmakiEPrintzaNTzimouliVPapachristouF.Safety and efficacy of rituximab in refractory pediatric systemic lupus erythematosus nephritis: a single-center experience of Northern Greece. Rheumatol Int2013; 33: 809–813.
21.
OlfatMSilvermanEDLevyDM.Rituximab therapy has a rapid and durable response for refractory cytopenia in childhood-onset systemic lupus erythematosus. Lupus2015; 24: 966–972.
22.
TambralliABeukelmanTCronRQStollML.Safety and efficacy of rituximab in childhood-onset systemic lupus erythematosus and other rheumatic diseases. J Rheumatol2015; 42: 541–546.
23.
WatsonLBeresfordMWMaynesC, et al. The indications, efficacy and adverse events of rituximab in a large cohort of patients with juvenile-onset SLE. Lupus2015; 24: 10–17.
24.
SahinSAdrovicABarutK, et al. Juvenile systemic lupus erythematosus in Turkey: demographic, clinical and laboratory features with disease activity and outcome. Lupus2018; 27: 514–519.
25.
Artim-EsenBŞahinSÇeneE, et al. Comparison of disease characteristics, organ damage, and survival in patients with juvenile-onset and adult-onset systemic lupus erythematosus in a combined cohort from 2 tertiary centers in Turkey. J Rheumatol2017; 44: 619–625.
26.
BasuBRoyBBabuBG.Efficacy and safety of rituximab in comparison with common induction therapies in pediatric active lupus nephritis. Pediatr Nephrol2017; 32: 1013–1021.
27.
MenonSHariPBaggaA.Beneficial effects of rituximab therapy for systemic lupus erythematosus. Indian J Pediatr2007; 74: 79–82.
28.
AlE’edAAlSonbulAAl-MayoufSM.Safety and efficacy of combined cyclophosphamide and rituximab treatment in recalcitrant childhood lupus. Rheumatol Int2014; 34: 529–533.
29.
FanouriakisAKostopoulouMCheemaK, et al. 2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis. Ann Rheum Dis2020; 79: 713–723.
30.
MahmoudIJellouliMBoukhrisI, et al. Efficacy and safety of rituximab in the management of pediatric systemic lupus erythematosus: a systematic review. J Pediatrics2017; 187: 213–219 e2.
