Session Information
Date: Tuesday, November 10, 2015
Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy Poster III
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose:
The investigational agent sarilumab is a human mAb directed against the IL-6
receptor. In the phase 3 MOBILITY study (NCT01061736), sarilumab (150 or 200 mg
every 2 wks [q2w] + MTX) demonstrated efficacy in adults with active, moderate-to-severe
RA with inadequate response to MTX.1 The
most common treatment-emergent adverse events (TEAEs) with sarilumab included
infections, neutropenia, injection site reactions, and increased transaminases.
Lab changes observed were consistent with IL-6 signaling blockade. This
analysis examined dose reduction of sarilumab that occurred during an open-label,
long-term, follow-up study (EXTEND, NCT01146652)
that evaluates long-term safety and efficacy of sarilumab with or without
concomitant non-biologic DMARDs. Eligible patients were adults with RA who
participated in prior sarilumab studies.
Methods: Patients initially entering
EXTEND received sarilumab 150 mg every week (qw). Following dose selection for
phase 3 studies, patients were switched to or initiated on sarilumab 200 mg
q2w. Per protocol, investigators could have reduced the dose to sarilumab 150
mg q2w for absolute neutrophil count (ANC) ≥0.5 to 1.0 Giga/L in the
absence of infection, platelet count ≥50 to 100 Giga/L in the absence of
bleeding, or alanine aminotransferase (ALT) ≥3 to 5 × ULN. The majority
of patients included in these analyses were enrolled from MOBILITY; efficacy
data from EXTEND were analyzed after dose reduction in these patients (n=138).
Results: The study is ongoing. As of
April 2015 interim analysis, dose reduction from 200 to 150 mg sarilumab q2w
occurred in 15% of patients. The most common reasons for sarilumab dose
reduction were decrease in neutrophil counts (9.5%) and elevations in ALT (3.3%)
(Table 1). Infection
was the most common non-laboratory reason for dose reduction (0.4%). Approximately
76% of patients who dose reduced are continuing treatment, with a mean duration
of treatment after dose reduction of 1.5 years. Improvements in ANC and ALT
were observed over the 6 months following dose reduction (Table 2). Efficacy of
sarilumab in MOBILITY patients was maintained following dose reduction in
EXTEND as assessed by ACR20 response at wk 24: 83%.
Conclusion:
In this study, reducing the dose from 200 mg q2w to 150 mg q2w to manage
laboratory abnormalities allowed the majority of patients to continue in the study
for a mean duration of >1.5 years. For patients continuing in the study,
these laboratory abnormalities improved during the 6 months following dose
reduction, and efficacy was maintained.
1. Genovese et al. Arthritis Rheumatol.
2015;67:1424-1437.
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Table 1. Reasons for Dose Reduction
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Patients on 200 mg q2w (N=1843) n (%)
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Patients who dose reduced from 200 mg q2w to 150 mg q2w
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276 (15%) |
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Decrease in neutrophil count Neutrophil count <1.0 Giga/L and ≥0.5 Giga/L Precautionary measure to avoid ANC <1.0 Giga/L
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175 (9.5%) 92 (5.0%) 83 (4.5%) |
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Increase in ALT level ALT increase >3 times ULN and ≤5 times ULN Precautionary measure to avoid ALT increase >3 times ULN |
61 (3.3%) 54 (2.9%) 7 (0.4%) |
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Decrease in platelet count Platelet count ≥50 Giga/L and <100 Giga/L Precautionary measure to avoid platelet count <100 Giga/L |
19 (1.0%) 8 (0.4%) 11 (0.6%) |
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Other AE |
16 (0.9%) |
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Other reason |
5 (0.3%) |
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AE, adverse event; ALT, alanine aminotransferase; q2w, every 2 weeks; ULN, upper limit of normal. |
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Table 2. Laboratory Parameters Following Dose Reduction
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Prior to dose reduction n (%)
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1 month after dose reduction n (%)
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3 months after dose reduction n (%)
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6 months after dose reduction n (%)
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Absolute neutrophil count |
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≥0.5 to 1.0 Giga/L |
95/175 (54%) |
17/121 (14%) |
17/146 (12%) |
8/131 (6%) |
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<0.5 Giga/L |
0/175 |
3/121 (3%) |
1/146 (1%) |
0/131 |
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ALT |
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>3 and ≤5 times ULN |
50/61 (82%) |
7/34 (21%) |
1/46 (2%) |
2/46 (4%) |
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>5 and ≤10 times ULN |
2/61 (3%) |
1/34 (3%) |
0/46 |
0/46 |
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ALT, alanine aminotransferase; ULN, upper limit of normal. |
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To cite this abstract in AMA style:
Burmester G, Garg A, van Hoogstraten H, Graham N, Boddy A, Parrino J, Genovese MC. Sarilumab Dose Reduction to Manage Laboratory Abnormalities in an Open-Label Extension Study in RA Patients [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/sarilumab-dose-reduction-to-manage-laboratory-abnormalities-in-an-open-label-extension-study-in-ra-patients/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/sarilumab-dose-reduction-to-manage-laboratory-abnormalities-in-an-open-label-extension-study-in-ra-patients/