Short-term efficacy and safety of rituximab therapy in refractory systemic lupus erythematosus: results from the British Isles Lupus Assessment Group Biologics Register

Abstract

Objectives: To describe the baseline characteristics of SLE patients requiring biologic therapy in the UK and to explore short term efficacy and infection rates associated with rituximab (RTX) use.

Methods: Patients commencing biologic therapy for refractory SLE and who consented to join BILAG-BR were analysed. Baseline characteristics, disease activity (BILAG 2004/SLEDAI-2K) and rates of infection over follow-up were analysed. Response was defined as loss of all A and B BILAG scores to ⩽ 1 B score with no new A/B scores in other organ systems at 6 months.

Results: Two hundred and seventy SLE patients commenced biologic therapy from September 2010 to September 2015, most commonly RTX (n = 261). Two hundred and fifty (93%) patients were taking glucocorticoids at baseline at a median [interquartile range (IQR)] oral dose of 10 mg (5-20 mg) daily. Response rates at 6 months were available for 68% of patients. The median (IQR) BILAG score was 15 (10-23) at baseline and 3 (2-12) at 6 months (P < 0.0001). The median (IQR) SLEDAI-2K reduced from 8 (5-12) to 4 (0-7) (P < 0.001). Response was achieved in 49% of patients. There was also a reduction in glucocorticoid use to a median (IQR) dose of 7.5 mg (5-12 mg) at 6 months (P < 0.001). Serious infections occurred in 26 (10%) patients, being more frequent in the first 3 months post-RTX therapy. A higher proportion of early infections were non-respiratory (odds ratio = 1.98, 95% CI: 0.99, 3.9; P = 0.049).

Conclusion: RTX is safe and is associated with improvement in disease activity in refractory SLE patients with concomitant reductions in glucocorticoid use. Early vigilance for infection post-infusion is important to further improve treatment risks and benefits.

Fig. 1

Baseline disease activity scores for SLE patients upon entry into register (A) Number of individual patients scoring either an A or B on BILAG-2004 scoring system across the systems assessed. (B) Number of individual patients scoring one or more points across the systems assessed by SLEDAI-2K. CNS includes seizure, psychosis, organic brain syndrome, visual disturbance, cranial nerve disorder, lupus headache and stroke. Renal includes proteinuria, haematuria, urinary casts and pyuria. Serositis includes both pleurisy and pericarditis. Serology included low complement and/or elevated dsDNA either alone or in combination. Cardioresp.: Cardiorespiratory; Con.: Constitutional; GI: gastrointestinal; Haem.: haematological; Muc.: mucocutaneous; MSK: musculoskeletal; Neuro.:Neurological; Ophthal.: Ophthalmic.

Fig. 2

Rates of damage and comorbidity in SLE patients requiring rituximab therapy (A) Frequency of SLE patients scoring one or more points across the individual domains assessed by SLICC-SDI. (B) Frequency of comorbid conditions in SLE patients at time of rituximab therapy. GI: gastrointestinal; MSK: musculoskeletal; Pulm: pulmonary; PVD: peripheal vascular disease.

Fig. 3

Rates of response to rituximab therapy in refractory SLE The percentage of patients (n = 178) with improvement, persistent disease activity and deterioration in disease activity following rituximab therapy at 3 and 6 months as assessed by (A) BILAG 2004 Index vs baseline assessment and (B) SLEDAI-2K. (C) The number of patients with persistent disease or new organ involvement at 6-month assessment as per BILAG organ domain. GI: gastrointestinal; MSK: musculoskeletal.

Fig. 4

Rituximab treatment is associated with an increased risk of infection Rates of (A) all and (B) serious infections post-rituximab treatment in SLE patients. (C) The rate of all infections declined over time with (D) the excess infection burden in the first 3 months being attributed to non-respiratory infections. GI: gastrointestinal.