IMPROVED HEALTH-RELATED QUALITY OF LIFE (HRQOL) FOLLOWING SUSTAINED REDUCTIONS IN ANTI-DSDNA ANTIBODIES IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) AFTER TREATMENT WITH LJP394

V Strand, B Crawford

OBJECTIVE: Treatment with LJP 394 has been associated with decreased anti-dsDNA Ab levels in patients with SLE. Sustained reductions were demonstrated in 2 placebo randomized controlled trials of 298 (phase 3) and 189 (phase 2/3) SLE patients with a history of renal disease, statistically favoring active vs placebo treatment. SF-36 was assessed at baseline, 6 and 12 months in phase 3; baseline and 4 months in phase 2/3 protocols, respectively, to evaluate the impact of sustained reductions on patient reported HRQOL.

METHODS: Sustained reductions: ≥20% decreases from baseline in ≥2/3 of all anti-dsDNA Ab determinations defined ‘responders’; after treatment with high-dose corticosteroids and/or cyclophosphamide, values were imputed to baseline. Sustained reductions by ≥10% and ≥20% similarly identified responders with active treatment; 20% better differentiated LJP394 from placebo at 12 months and endpoint. Minimal clinically important differences (MCID) were based on a 15-point global change scale, after Guyatt et al, corresponding to improvement by a score of 6: "A Little Better".

RESULTS: In phase 3, 31.4% patients were responders (91 vs 199 non-responders), 63 in LJP394, 28 in placebo; a ratio of 2.25 favoring active treatment. At 6 months, 31.3% were responders: 59 LJP394 and 27 placebo; a ratio of 2.2. At 6 months, responders reported improvement in all domains of SF-36 with the largest increases in bodily pain (8.2), vitality (8.0), general health perceptions (6.6) and physical function (5.7). Non-responders reported worsening in all but 3 domains which remained unchanged (vitality (1.3), mental health (0.9), and role emotional (0.0)). At 12 months, 43 LJP394 and 24 placebo treated patients were responders; a ratio of 1.8; 35.3% overall. Improvements reported by responders increased by month 12, with largest changes in role physical (13.8), vitality (10.2), general health profile (9.3), and bodily pain (7.3), again with no change or deterioration in non-responders. Improvements in domain scores were reflected in physical component summary (PCS) score. Results were similar after removal from the analyses of patients with renal flares or who received high dose corticosteroids and/or cyclophosphamide. Similar improvements were reported by responders in the phase 2/3 protocol at 4 months. MCID was determined to range from 6.7 to 11.4 points in domain and 3.4 to 3.9 in PCS scores, consistent with literature reported estimates of 5-10 and 2.5-5.0 points.

CONCLUSION: Sustained reductions in anti-dsDNA Ab levels lead to improvement in patient reported HRQOL. These improvements are clinically meaningful, regardless of treatment group. LJP394 administration resulted in 1.8 to 4.0 times more responders than placebo.

Presented at the
7th International Lupus Congress
New York, NY
May 9-13, 2004