Abarna Thangaraj MD, DNB, DM (Pediatric Clinical Immunology and Rheumatology), MNAMS
Consultant Immunologist and Pediatric Rheumatologist, KIMS Cuddles, Hyderabad, Telangana
Severe, organ-threatening manifestations of systemic vasculitis or connective tissue disease are associated with high morbidity and mortality. Current guidelines recommend either rituximab or cyclophosphamide for severe rheumatological illness.
Rife et al evaluated the safety and effectiveness of combination rituximab (RTX) and cyclophosphamide (CYC) therapy in pediatric patients with severe rheumatic diseases. It is a single-centre retrospective study, conducted at the University of Alabama at Birmingham/Children’s of Alabama between January 2010 and February 2023. The study included 89 patients with a median age of 14 years. The majority (66%) were diagnosed with systemic lupus erythematosus (SLE), while others had ANCA-associated vasculitis (6.7%) and other rheumatological illnesses. The most common treatment indication of combination therapy was nephritis (61%), predominantly class 4 lupus nephritis, followed by neurological manifestations (20%).
Patients received a median of 4 RTX doses and 6 CYC doses during the 12-month follow-up. There were no deaths during the study period, and only 8 patients (8.9%) required hospitalisation for infection. They have also noticed the significant reduction in dsDNA and complement levels. Glucocorticoid (GC) use declined sharply, and 62% of patients discontinued GCs entirely by the end of follow-up. Disease flare occurred in 6 patients (6.7%), while 11 patients (12%) experienced infusion reactions. Of 89 patients, 26 (31%) developed hypogammaglobulinemia.
The study concludes that RTX/CYC combination therapy is generally safe, reduces steroid burden, and effectively controls disease activity in children with severe rheumatic conditions. However, this requires further randomised controlled trials to validate these findings and compare outcomes against standard monotherapy approaches.
JIA is the most common chronic rheumatic disease in children and often persists into adulthood. Traditional step-up therapy begins with NSAIDs and steroids, followed by conventional DMARDs and, as a last resort, biologic therapy, which delays effective treatment. The UCAN CAN-DU study examined whether earlier initiation of biologic therapy improves outcomes in children with juvenile idiopathic arthritis (JIA).
A nested cohort within the UCAN CAN-DU international study (Canada, Netherlands) included 130 non-systemic JIA patients (66% female; median age 11). All were biologic-naive and started biologics within 24 months of symptom onset. Patients were grouped by time to biologic: Early (0–6 months): 35 patients, Intermediate (7–12 months): 46 patients and Late (13–24 months): 49 patients. Outcome measure was inactive arthritis (active joint count = 0) after 6 months of biologic therapy and secondary combined active joint count + physician global assessment (PhGA) < 1.
They found that inactive arthritis rates were 83% in early starters, 67% in intermediate starters, and 57% in late starters, with p=0.013 for early vs late biologic group. Each month of delay in introducing biologic increased the risk of persistent arthritis by 9% (adjusted OR 1.09; 95% CI 1.02 — 1.17; p=0.009). This study suggests that early biologic initiation within 6 months of symptom onset dramatically improves remission rates in childhood arthritis. These findings support a therapeutic window of opportunity, challenging step-up strategies in JIA.
