Effects of Belimumab on Flare Rate and Expected Damage Progression in Patients With Active Systemic Lupus Erythematosus

Abstract

Objective. To investigate effectiveness and safety of belimumab in patients with active systemic lupus erythematosus (SLE) in a clinical practice setting. Methods. Sixty-seven patients with active SLE, mean 6 SD age 39.3 6 10.2 years, from 2 Italian prospective cohorts were treated with belimumab (10 mg/kg on day 0, 14, 28, and then every 28 days) added to background therapy. The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), the Systemic Lupus International Collaborating Clinics/ American College of Rheumatology Damage Index, the Disease Activity Score in 28 joints (DAS28), 24-hour proteinuria, the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score, anti-double-stranded DNA (antidsDNA), C3 and C4 levels, and prednisone daily dose were recorded at baseline, month 3, 6, 9, 12, 18, and 24. Arthritis was subdivided into "classical" (CLP) and "rheumatoid-like"; skin manifestations into acute (ACLE), subacute (SCLE), and chronic. SLE flares, defined according to the SLEDAI Flare Index, were calculated before and after belimumab initiation. Adverse events were carefully evaluated during treatment. Statistics were performed by the SPSS package (version 21.0). Results. Mean 6 SD followup was 16.2 6 9.5 months. Main refractory manifestations treated with belimumab were musculoskeletal (37.3%), mucocutaneous (22.4%), and renal (23.9%). SLEDAI-2K, prednisone daily dose, anti-dsDNA, DAS28, CLASI, and 24-hour proteinuria decreased during treatment. DAS28 score decreased in patients with polyarthritis (P < 0.001), particularly in those with CLP (P < 0.001), and CLASI decreased in patients with skin manifestation (P 5 0.003), either ACLE (P 5 0.051) or SCLE (P 5 0.047). Flare rate was lower 1 and 2 years after belimumab initiation than in the periods before (P 5 0.001). Belimumab was well-tolerated and no damage accrual was observed after initiation. Conclusion. Belimumab was effective and safe in a clinical practice setting; it decreased the number of flares and hindered damage progression in patients with active SLE.

Aiolos Overexpression in Systemic Lupus Erythematosus B Cell Subtypes and BAFF-Induced Memory B Cell Differentiation Are Reduced by CC-220 Modulation of Cereblon Activity

“…In support of this concept, clinical benefit of direct B cell depletion (122) and indirect B cell modulation by Ab blockade of BAFF has been reported (123). Other factors such as IFN-a may also have a link to B cell-driven SLE pathology.…”

When to use belimumab in SLE

“…Several case series and case reports and subsequently a large multicenter observational study have been carried out after BLISS trials [2][3][4][5][6][7][8][9][10] (Table 1), all converging on belimumab being able to improve control of disease activity and reduce daily corticosteroid intake, which are indeed expected to reduce organ damage in the long term. Unfortunately, those studies did not systematically measure disease activity according to approved scores, as retrospective observations were performed that were influenced by clinical practice.…”

“…Subsequently, we published the first prospective study on belimumab use as on-top treatment in SLE with a 24-month follow-up, including a real-world population, that is, patients attending our outpatient clinic, with no restrictions in previous drug use or comorbidities, except the presence of severe SLE manifestations that per se prevent patients from accessing belimumab in our cohort [7]. Our results were in line with those from pioneer studies and post hoc analysis on the BLISS population, finding out that belimumab is able to reduce disease flares, control disease activity in the mid-and long term, and significantly decrease daily corticosteroid intake.…”

“…Importantly, relevant real-life experience [4,6,7,9] as well as a 7-year long-term extension study involving patients coming from the phase 2 RCT who had had an improvement in physician global assessment (PGA) since baseline proved a long-standing disease control and decrease in flare rate during the overall 7-year observation on belimumab treatment [17], suggesting such positive effects are long-lasting. Notably, published studies including RCT, long-term extensions studies and real-life experience underlined a good safety and tolerability profile of belimumub use even when added to immunosuppressive therapy.…”

“…Importantly, as a reduction in SLE flares was extensively reported [2][3][4][5][6][7][8], it looks advisable to prompt belimumab especially in patients displaying a relapsing-remitting disease pattern, in whom a significant decrease in flare rate is among the fundamental treatment goals.…”