What Does It Mean to Be a British Isles Lupus Assessment Group-Based Composite Lupus Assessment Responder? Post Hoc Analysis of Two Phase III Trials

Abstract

Objective: The British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) is a validated global measure of treatment response in systemic lupus erythematosus (SLE) clinical trials. To understand the relevance of BICLA in clinical practice, we investigated relationships between BICLA response and routine SLE assessments, patient-reported outcomes (PROs), and medical resource utilization.

Methods: This was a post hoc analysis of pooled data from the phase III, randomized, placebo-controlled, 52-week TULIP-1 (ClinicalTrials.gov identifier: NCT02446912; n = 457) and TULIP-2 (ClinicalTrials.gov identifier: NCT02446899; n = 362) trials of intravenous anifrolumab (150/300 mg once every 4 weeks) in patients with moderate-to-severe SLE. Changes from baseline to week 52 in clinical assessments, PROs, and medical resource use were compared in BICLA responders versus nonresponders, regardless of treatment assignment.

Results: BICLA responders (n = 318) achieved significantly improved outcomes compared with nonresponders (n = 501), including lower flare rates, higher rates of attainment of sustained oral glucocorticoid taper to ≤7.5 mg/day, greater improvements in PROs (Functional Assessment of Chronic Illness Therapy-Fatigue, Short Form 36 Health Survey), and fewer SLE-related hospitalizations/emergency department visits (all nominal P < 0.001). Compared with nonresponders, BICLA responders had greater improvements in global and organ-specific disease activity (Physician's Global Assessment, SLE Disease Activity Index 2000, Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity, and joint counts; all nominal P < 0.001). BICLA responders had fewer lupus-related serious adverse events than nonresponders.

Conclusion: BICLA response is associated with clinical benefit in SLE assessments, PROs, and medical resource utilization, confirming its value as a clinical trial end point that is associated with measures important to patient care.

Figure 1

Flares and oral glucocorticoid (GC) use in British Isles Lupus Assessment Group (BILAG)–based Composite Lupus Assessment (BICLA) responders compared with nonresponders. A, Patients with ≥1 BILAG 2004 flare through week 52. Bars show the mean and 95% confidence interval (95% CI). B, Least squares mean (LSM) change in oral glucocorticoid daily dosage from baseline to week 52 in all patients regardless of baseline oral glucocorticoid dosage. Bars show the LSM change and 95% CI. C, Patients achieving sustained oral glucocorticoid dosage reduction to ≤7.5 mg/day among patients receiving oral glucocorticoids ≥10 mg/day at baseline. Sustained oral glucocorticoid dosage reduction is defined as oral glucocorticoid dosage of ≤7.5 mg/day sustained from weeks 40 to 52. Bars show the mean and 95% CI. D, Oral glucocorticoids area under the curve (AUC) through week 52 for all patients regardless of baseline oral glucocorticoid dosage. Bars show the mean ± SD. Rate difference, 95% CIs, and nominal P values were calculated using a stratified Cochran‐Mantel‐Haenszel approach.

Figure 2

Patient‐reported outcomes at week 52 in BICLA responders compared with nonresponders. A–C, Patients with a response according to following assessments: the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT–F), defined as an improvement of >3 points from baseline to week 52 (A), Short Form 36 health survey (SF‐36) physical component summary (PCS), defined as an increase of >3.4 in the PCS domain from baseline to week 52 (B), and SF‐36 mental component summary (MCS), defined as an increase of >4.6 in the MCS domain from baseline to week 52 (C). Bars show the mean and 95% CI. Response rates, 95% CIs, and nominal P values were calculated using a stratified Cochran‐Mantel‐Haenszel approach. D, LSM change in patient global assessment (PtGA) score from baseline to week 52. Bars show the LSM change and 95% CI. LSM difference, 95% CIs, and nominal P values were calculated using mixed‐model repeated measures. See Figure 1 for other definitions.

Figure 3

Change in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI‐2K) (A) and physician global assessment (PhGA) scores (B) from baseline to week 52 in BICLA responders compared with nonresponders. Bars show the mean and 95% CI. LSM difference, 95% CIs, and nominal P values were calculated using mixed‐model repeated measures. See Figure 1 for other definitions.

Figure 4

Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) response and joint counts in BICLA responders compared with nonresponders. A, Patients with a CLASI response at week 52 (defined as ≥50% reduction from baseline to week 52) among patients with a CLASI activity score of ≥10 at baseline. Bars show the mean and 95% CI. Response rates, 95% CIs, and nominal P values were calculated using a stratified Cochran‐Mantel‐Haenszel approach. B, Change in LSM joint counts from baseline to week 52 for active joints (defined as a joint with swelling and tenderness), tender joints, and swollen joints. Bars show the mean and 95% CI. LSM difference, 95% CIs, and nominal P values were calculated using mixed‐model repeated measures. See Figure 1 for other definitions.