PO:16:232 | Belimumab step-down dose spacing in patients with systemic lupus erythematosus in persistent clinical remission: experience from a multicentric cohort

Alice Bartoletti¹, Laura Giudice¹, Lorenza Maria Argolini^1|2, Giuseppe Alvise Ramirez³, Luca Moroni³, Tommaso Schioppo⁴, Chiara Bellocchi^5|6, Annalaura Fasiello⁶, Lorenzo Beretta⁶, Lorenzo Dagna³, Roberto Caporali¹, Maria Gerosa¹. | ¹UO Clinica Reumatologica, ASST Gaetano Pini CTO, Milano, Italy; ²UOC Medicina fisica e riabilitazione specialistica, ASST Gaetano Pini CTO, Milano, Italy; ³Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, Vita-Salute San Raffa Milano Italy; ⁴Medicina Generale II, Servizio di Reumatologia, Ospedale San Paolo, ASST Santi Paolo Carlo, Milano, Italy; ⁵Department of Clinical Sciences and Community Health, University of Milan, Dipartimeto di Eccellenza 2023-2027, Milano, Italy; ⁶Referral Centre for Systemic Autoimmune DIseases, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy

Background. To evaluate the feasibility and safety of belimumab (BEL) dose spacing and withdrawal in patients with systemic lupus erythematosus (SLE) who were in long-standing remission on BEL.

Methods. Patients above 18 years of age with a diagnosis of SLE and persistent disease remission while on BEL were enrolled. Persistent remission was defined as >6 months on stable immunosuppressive therapy without experiencing a clinical flare of SLE (i.e. clinical SLE disease activity index [C-SLEDAI] less or equal to 2). All the patients started BEL spacing at enrolment. Patients were assessed by an experienced rheumatologist with physical examinations and laboratory tests every 12 weeks for 24 months for disease activity and damage accrual according to Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index. If the patient was in clinical remission (C-SLEDAI less or equal to 2 and absent [British Isles Lupus Assessment Group] BILAG A or B items), BEL was tapered as follows: - Step 1: BEL 200 mg subcutaneous (SC) every 10 days OR 10 mg/Kg intravenous (IV) every 6 weeks - Step 2: BEL 200 mg SC every 14 days OR 10 mg/Kg IV every 8 weeks - Step 3: BEL 200 mg SC every 21 days OR 10 mg/Kg IV every 12 weeks - Step 4: stop BEL Primary outcome: number of disease flares during follow-up. Secondary outcomes: progression of SLICC/ACR damage index, death.

Results. Twenty-two patients were enrolled (Table 1), 21 were females (95.5%), with a mean age of 48±10 years. Mean disease duration was 21±11 years. Seven patients (31.8%) had a history of lupus nephritis. At the start of BEL spacing, 6 patients were on glucocorticoid (GC) therapy at a mean dose of 4.4±1.7 mg/day Prednisone equivalents), and 15 were taking Hydroxychloroquine (HCQ). Patients were treated with BEL for an average of 6±3 years before enrolment. Patients were observed for a median of 21 (Q1–Q3: 16–24) months. Five patients were stopped BEL during follow-up. One patient on BEL SC every 14 days experienced a disease relapse (C-SLEDAI 4) and was started HCQ at 15 months. One patient who stopped BEL had a C-SLEDAI of 1 and low complement at baseline and during the follow-up. She developed anti-dsDNA positivity and was initiated Azathioprine at month 21. None of the patients had to return to the previous BEL step nor required an increase in GC dose. No major disease relapses, deaths nor increases in SLICC/ACR organ damage index were reported during the follow-up.

Conclusion. Progressive BEL dose spacing and withdrawal, paired with close monitoring for disease activity, can be a feasible and safe approach for SLE patients in long-standing remission on BEL.