Patients with higher BLyS levels (?2?ng/mL), who are most at risk of SLE flare, had generally poorer responses to standard SLE care alone, and derived a greater benefit from belimumab treatment; this was demonstrated by the numerically greater treatment differences for belimumab versus placebo for these patients, compared with the BLyS? ?2?ng/mL group, though no statistical analyses compared the efficacy of belimumab in these two patient categories

Patients with higher BLyS levels (?2?ng/mL), who are most at risk of SLE flare, had generally poorer responses to standard SLE care alone, and derived a greater benefit from belimumab treatment; this was demonstrated by the numerically greater treatment differences for belimumab versus placebo for these patients, compared with the BLyS? ?2?ng/mL group, though no statistical analyses compared the efficacy of belimumab in these two patient categories. C3 ( ?900?mg/L), anti-dsDNA 80C200?IU/mL and ?200?IU/mL, immunosuppressant usage, proteinuria, elevated C-reactive protein (CRP; 3?mg/L), and low total lymphocyte count (Table 2). Table 2 Baseline predictors of baseline BLyS levels??2?ng/mL in the stepwise logistic regression analysis (regression analysis population) (%)53 (39.0)21 (17.4)78 (18.6)66 (15.3)Median time to severe SLE flare (range), daysNA (1C360)cNA (10C323)cNA (5C371)cNA (1C366)cHR versus placebo (95% CI)b0.37 (0.22, 0.63)0.81 (0.58, 1.12)(%)9/76 (11.8)16/79 (20.3)37/240 (15.4)55/240 (22.9)Difference versus placebo8.417.50OR (95% CI); (%)25/60 (41.7)13/42 (31.0)54/179 (30.2)51/192 (26.6)Difference versus placeboC10.7C3.61OR (95% CI); (%)77 (56.6)87 (71.9)289 (69.0)326 (75.5)Difference versus placebo15.36.5OR (95% CI); (%)a126 (92.6)115 (95.0)384 (91.6)395 (91.4)Headache24 (17.6)24 (19.8)89 (21.2)83 (19.2)Upper respiratory tract infection22 (16.2)19 (15.7)81 (19.3)71 (16.4)Nausea12 (8.8)24 (19.8)46 (11.0)42 (9.7)Urinary tract infection14 (10.3)18 (14.9)53 (12.6)51 (11.8)Arthralgia15 (11.0)15 (12.4)62 (14.8)56 (13.0)Diarrhea7 (5.1)15 (12.4)39 (9.3)47 Comp (10.9)Nasopharyngitis10 (7.4)14 (11.6)36 (8.6)49 (11.3)Anemia11 (8.1)13 (10.7)20 (4.8)15 (3.5)Cough14 (10.3)12 (9.9)26 (6.2)30 (6.9)Pyrexia12 (8.8)13 (10.7)26 (6.2)36 (8.3)Edema peripheral10 (7.4)13 (10.7)32 (7.6)29 (6.7)Hypertension14 (10.3)7 (5.8)35 (8.4)25 (5.8)Any SAE, (%)32 (23.5)25 (20.7)57 (13.6)76 (17.6)Any treatment-related AE, (%)58 MKT 077 (42.6)48 (39.7)174 (41.5)158 (36.6)AEs resulting in study discontinuation, MKT 077 (%)22 (16.2)10 (8.3)20 (4.8)27 (6.3)SAEs resulting in study discontinuation, (%)13 (9.6)9 (7.4)13 (3.1)17 (3.9) Open in a separate window AE: adverse event; BLyS: B-lymphocyte stimulator; SAE: serious adverse event. aOnly AEs occurring in??10% of patients in any treatment arm are listed. Discussion BLyS levels??2?ng/mL have been found to be predictive of SLE flare over 52 weeks;9 however, BLyS levels are not routinely or easily measured in clinical practice. This post hoc regression analysis of baseline data from two Phase III clinical trials (BLISS-52 and -76) identified routinely-collected clinical measures that could be used as surrogate markers of serum BLyS levels??2?ng/mL: positive anti-Smith (?15 U/mL), low C3 ( ?900?mg/L), anti-dsDNA 80C200?IU/mL and??200?IU/mL, the use of immunosuppressant medication, proteinuria, elevated CRP, and low total lymphocyte count. Taking these parameters into consideration may help healthcare professionals identify patients with SLE who are at risk of flare and manage their treatment plan accordingly.9 The BLISS trials demonstrated MKT 077 the efficacy of belimumab (10?mg/kg).7,8 This post hoc analysis of those trials compared belimumab 10?mg/kg (plus standard SLE care) versus placebo (plus standard SLE care) in patients with BLyS levels??2?ng/mL and BLyS levels? ?2?ng/mL. Approximately half of patients who received belimumab achieved an SRI response at Week 52 in the overall population, and this was consistent across both BLyS subgroups. The treatment differences versus placebo in SRI responses were numerically greater in patients with BLyS levels??2?ng/mL (difference versus placebo of 24.1%) compared with BLyS levels? ?2?ng/mL (difference versus placebo of 8.2%) and the 12% difference measured in the overall BLISS population.7,8 The differences in treatment response in the present study were brought about by the poorer response in the placebo arm in the BLyS??2?ng/mL group compared with the BLyS? ?2?ng/mL group. This suggests that patients with BLyS levels??2?ng/mL, who are at risk of flare,9 had a lesser response to standard treatment than those with BLyS levels? ?2?ng/mL, but benefited from belimumab, which specifically inhibits BLyS.11 There may be additional factors, other than the level of circulating BLyS, which play a role in this response. The overall percentage of patients who received belimumab and experienced a severe flare appeared to be similar between the two BLyS groups. However, in the placebo arms the BLyS??2?ng/mL group experienced a numerically greater incidence of severe flare compared with the BLyS? ?2?ng/mL group. This indicates that inhibition of BLyS MKT 077 lowered the risk of severe flare in the BLyS??2?ng/mL group to a level similar to that in the BLyS? ?2?ng/mL group. Indeed, the reduction in risk of severe SLE flare with belimumab 10?mg/kg plus standard care versus placebo was numerically greater in patients with BLyS levels??2?ng/mL (63%) compared with BLyS levels? ?2?ng/mL (19%). That BLyS levels??2?ng/mL are associated with.