Session Information
Date: Tuesday, October 23, 2018
Session Title: Systemic Lupus Erythematosus – Clinical Poster III: Treatment
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose:
We conducted an integrated analysis of pooled safety data from all 17 atacicept clinical studies to date, across multiple indications, to further define atacicept’s safety profile.
Methods:
Analyses were based on 3 pooled datasets: Double-blind placebo (PBO)-controlled set (DBPC-S n=1,568; key endpoint: treatment-emergent AEs [TEAEs]); SLE set (SLE-S n=761; key endpoint: IgG change and serious infection rates); full analysis set (FA-S n=1,845; key endpoint: exposure-adjusted mortality).
Results:
Of 1,568 patients in the DBPC-S, 30.8% received PBO, and 8.2%, 24.5% and 36.5% received atacicept 25, 75 and 150 mg, respectively. Overall, baseline characteristics were balanced across treatment arms. Treatment exposure was similar with PBO and atacicept 75 mg and 150 mg (278.3, 225.0 and 286.7 patient-years, respectively), but was lower with atacicept 25 mg (51.5 patient-years). Exposure-adjusted TEAE rates were generally higher with atacicept vs placebo, with no consistent association between atacicept dose and cardiac arrhythmias, serious and severe infections or injection site reactions (Table). Serious infection and serious TEAE rates were similar between atacicept and PBO. TEAE-related discontinuation rates were higher with atacicept versus placebo (16.1 vs 10.9/100 patient-years). In the SLE-S, there was no association between reduced IgG levels and increased infection rates. Across all studies (FA-S), 11 patients died during treatment (10 atacicept [0.5%], 1 PBO [0.1%]; see Table for infection-related deaths in the DBPC-S). Exposure-adjusted mortality rates/100 patient-years (95% CI) were 3.60 (0.90–14.38), 0.34 (0.05–2.43), 1.18 (0.49–2.82) for atacicept 25, 75 and 150 mg, and 0.44 (0.06–3.12) with PBO.
Conclusion:
Results from this pooled analysis clarify the benefit-risk relationship for atacicept, which is being further evaluated in additional clinical studies in IgA nephropathy and SLE.
| Table. Exposure-adjusted TEAE rates by dose (DBPC-S) | ||||||
| Atacicept | ||||||
| PBO n=483 | 25 mg, n=129 | 75 mg, n=384 | 150 mg, n=572 | All, n=1,085 | Total, n=1,568 | |
| Total number of patient-years | 278.3 | 51.5 | 225.0 | 286.7 | 563.2 | 841.4 |
| TEAE, n (per patient-years) | ||||||
| Hypersensitivity* | 37 (13.9) | 8 (15.7) | 40 (19.1) | 55 (20.4) | 103 (19.4) | 140 (17.6) |
| Infections | 211 (107.8) | 43 (104.4) | 180 (118.7) | 281 (141.3) | 504 (128.7) | 715 (121.7) |
| Herpes zoster | 13 (4.7) | 2 (3.9) | 10 (4.5) | 17 (6.1) | 29 (5.2) | 42 (5.1) |
| Serious infection | 20 (7.3) | 1 (1.9) | 23 (10.5) | 22 (7.7) | 46 (8.3) | 66 (7.9) |
| Severe infection | 9 (3.2) | 0 | 11 (4.9) | 16 (5.6) | 27 (4.8) | 36 (4.3) |
| Injection-site reactions | 54 (20.9) | 27 (64.8) | 109 (63.0) | 156 (72.4) | 292 (67.9) | 346 (50.2) |
| Severe hypogammaglobulinemia (IgG <3 g/L) | 0 | 0 | 2 (0.9) | 4 (1.4) | 6 (1.1) | 6 (0.7) |
| Cardiac arrhythmias [all]* | 18 (6.6) | 11 (22.4) | 23 (10.6) | 25 (8.9) | 59 (10.8) | 77 (9.4) |
| Ventricular arrhythmias | 5 (1.8) | 0 | 4 (1.8) | 6 (2.1) | 10 (1.8) | 15 (1.8) |
| Ischaemic heart disorders* | 11 (4.0) | 3 (5.9) | 13 (5.9) | 11 (3.9) | 27 (4.9) | 38 (4.6) |
| Embolic and thromboembolic events* | 11 (4.0) | 1 (2.0) | 6 (2.7) | 9 (3.2) | 16 (2.9) | 27 (3.2) |
| Vestibular disorders* | 19 (7.0) | 5 (9.9) | 18 (8.3) | 26 (9.3) | 49 (8.9) | 68 (8.3) |
| Demyelination* | 1 (0.4) | 1 (1.9) | 0 | 5 (1.7) | 6 (1.1) | 7 (0.8) |
| Depression* | 14 (5.1) | 3 (5.8) | 8 (3.6) | 11 (3.9) | 22 (3.9) | 36 (4.3) |
| Malignant tumour* | 0 | 1 (1.9) | 1 (0.4) | 3 (1.1) | 5 (0.9) | 5 (0.6) |
| Serious TEAE | 51 (18.9) | 15 (30.0) | 51 (23.9) | 61 (21.8) | 127 (23.4) | 178 (21.9) |
| Severe TEAE | 28 (10.2) | 10 (19.6) | 45 (20.9) | 56 (20.0) | 111 (20.3) | 139 (17.0) |
| Discontinuation of treatment due to TEAE | 30 (10.9) | 14 (27.6) | 30 (13.4) | 46 (16.1) | 90 (16.1) | 120 (14.3) |
| Deaths related to infections, n (%) | ||||||
| Deaths | 0 | 0 | 0 | 2 (0.3)† | 0 | 0 |
|
*Programmatically determined (crude results of the search) from a predefined list of MedDRA preferred terms according to the Standardized MedDRA Query (SMQ) or Customized MedDRA Query (CMQ) classification of the corresponding MedDRA version †Acute respiratory failure and probably leptospirosis (n=1); pneumonia and pulmonary alveolar haemorrhage (n=1) |
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To cite this abstract in AMA style:
Gordon C, Bassi R, Chang P, Kao AH, Jayne D, Wofsy D, Ona V, Fleuranceau-Morel P. Integrated Safety Profile of Atacicept from All Clinical Studies to Date [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/integrated-safety-profile-of-atacicept-from-all-clinical-studies-to-date/. Accessed October 25, 2021.« Back to 2018 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/integrated-safety-profile-of-atacicept-from-all-clinical-studies-to-date/