Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose:
Sarilumab is a human monoclonal antibody directed against the alpha subunit of the IL-6 receptor (IL-6Rα). IL-6 blockade is associated with a reduction in circulating neutrophil levels (CNL). It has been suggested that changes in CNL with IL-6 blockade may be due to margination of neutrophils or other mechanisms. The relationship between decrease in CNL and risk of infection is unclear.
Methods:
To evaluate the risk of neutropenia and infection with sarilumab, we retrospectively assessed clinical trial data from two 12-week Phase 2b studies in patients with RA (MOBILITY Part A [NCT01061736]) and with AS (ALIGN [NCT NCT01061723]). In these studies, patients were randomized to 6 groups: placebo (PBO), sarilumab 100 mg, 150 mg, 200 mg every other week (q2w) and 100 mg, 150 mg weekly (qw). CNL were determined q2w and incidence of total, serious, viral, fungal and bacterial infections were recorded. Data were analyzed across the PBO and sarilumab groups, with a focus on the 150 mg and 200 mg q2w dose regimens that were subsequently chosen for study in phase 3.
Results:
Three hundred six patients were enrolled in MOBILITY Part A (80% female; median age, 54 yrs [19:74]). 300 patients were enrolled in ALIGN (30% female; median age, 40 yrs [18:72]). One serious infection was reported in the 100 mg qw group of the ALIGN study. All other reported infections in both studies were non serious. Percent of patients with reported infections in the 6 dose groups above were 14, 12, 23, 26, 24, and 20% in MOBILITY and 18, 27, 22, 25, 18, and 29% in ALIGN. Infection rates in the Pbo groups and according to CNL in the pooled 150 mg (n = 103) and 200 mg (n = 100) q2w dose groups are presented in the Table. Infections in patients on sarilumab were most often observed among patients with normal CNL.
Conclusion:
In these 12 week studies, decreases in CNL did not appear to be associated with infection risk. This may be due to CNL margination or other mechanisms. These preliminary results warrant further exploration in the larger, longer phase 3 studies with sarilumab in patients with RA currently in progress.
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Number (%) of Patients With Infection From Baseline to Week 12 in MOBILITY Part A (RA) and ALIGN (AS): in Placebo Group; in Pooled Sarilumab 150mg q2w and 200mg q2w Dose Groups by Lowest Post-Baseline Circulating Neutrophil Level (CNL) |
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MOBILITY (150 mg q2w and 200 mg q2w |
Normal CNL N=69 |
Grade 1 CNL |
Grade 2 CNL |
Grade 3 & 4 CNL |
Pbo N=51 |
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Any Infection |
20 (29%) |
2 (15%) |
1 (8%) |
1 (14%) |
7 (14%) |
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Viral* |
4 (6%) |
0 |
0 |
0 |
0 |
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Fungal* |
1 (2%) |
0 |
0 |
0 |
0 |
|
Bacterial* |
1 (2%) |
1 (8%) |
0 |
1 (14%) |
0 |
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ALIGN (150 mg q2w and 200 mg q2w) |
Normal CNL N=55 |
Grade 1 CNL |
Grade 2 CNL |
Grade 3 & 4 CNL |
Pbo N=50 |
|
Any Infection |
15 (27%) |
2 (13%) |
2 (11%) |
2 (18%) |
9 (18%) |
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Viral* |
5 (9%) |
0 |
0 |
1 (9%) |
3 (6%) |
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Fungal* |
0 |
1 (6%) |
0 |
0 |
0 |
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Bacterial* |
0 |
0 |
0 |
0 |
1 (2%) |
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* Coded by etiology when provided à infections by etiology do not sum to total number of infections |
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Disclosure:
K. L. Winthrop,
Pfizer Inc,
2,
Genentech Inc., Pfizer, UCB, Regeneron,
5;
T. Momtahen,
Sanofi-Aventis Pharmaceutical,
3,
Sanofi-Aventis Pharmaceutical,
1;
S. Fiore,
Sanofi-Aventis Pharmaceutical,
3;
S. P. Weinstein,
Regeneron,
3,
Regeneron,
1;
J. van Adelsberg,
Regeneron,
3,
Regeneron,
1;
R. Wu,
Regeneron,
3,
Regeneron,
1;
N. Graham,
Regeneron,
3,
Regeneron,
1.
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