Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose:
Tabalumab, a monoclonal antibody that neutralizes membrane-bound and soluble B cell activating factor (BAFF), has been shown to reduce rheumatoid arthritis (RA) signs and symptoms1. This open-label study evaluated the long-term safety and efficacy of tabalumab in RA patients (pts).
Methods:
This 52-week (wk), open-label, flexible-dose extension study enrolled pts who completed 24 wks of a randomized, controlled trial (RCT) of tabalumab vs placebo (pb) and received study drug for ≥6 or 12 wks. Pts remained on stable MTX doses throughout. In RCT 1, pts received pb or tabalumab 30 or 80 mg IV every 3 wks for 6 wks and followed-up for 18 wks. In RCT 2, pts received pb or tabalumab 1, 3, 10, 30, 60, or 120 mg SC every 4 wks (Q4W) for 24 wks. At extension study start, all pts received SC tabalumab 60 mg Q4W for 48 wks; a 1-time increase to tabalumab 120 mg Q4W (60/120 mg) and 1-time decrease to 60 mg Q4W per pt was allowed (60/120/60 mg).
Results:
Of those who completed RCT 1 or 2, 98% (N=182, safety population) enrolled: tabalumab 60 mg (n=60), tabalumab 60/120 mg (n=121), and 1 pt after taking tabalumab 120 mg then returned to 60 mg. Baseline (pre-tabalumab) RA activity levels were generally higher for the 60/120 mg group. Overall, both groups appeared to maintain efficacy with long-term treatment (Table 1). One pt died due to myocardial infarction (60/120 mg). In each group, 5% discontinued due to an adverse event (AE). There was a higher frequency of serious AEs (SAEs) and treatment-emergent AEs (TEAEs, including severe events) as well as events of interest, including infections and injection-site reactions in the 60/120 mg group. Most infections involved the upper respiratory tract. One pt (60/120 mg) reported a fungal skin infection. No clinically significant differences in hematologic or chemistry values, vital signs, or ECGs were seen. Total B lymphocyte counts decreased by ~40% from pre-tabalumab baseline for all groups. The incidence of treatment-emergent, anti-tabalumab antibodies was 4.4% (8/182). Table 2 shows more detailed safety data.
Conclusion:
Despite prior treatment differences, the majority of pts in both treatment groups appeared to maintain efficacy response with long-term, open-label tabalumab treatment. No unexpected safety signals were observed, although a higher frequency of SAEs and severe TEAEs were observed in the 60/120 mg group. Reductions in total B cells were consistent with prior tabalumab studies.
1Genovese et al. [abstract]. Arthritis Rheum 2009;60 Suppl 10:1923
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Table 1. Efficacy Outcomes In Extension Study |
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Tabalumab (60 mg) N=59 |
Tabalumab (60/120 mg) N=120 |
All Patients N=180b,c |
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Week 24 |
Week 52a |
Week 24 |
Week 52a |
Week 24 |
Week 52a |
|
|
ACR20 response, % |
69.6 |
66.1 |
40.7 |
32.5 |
50.0 |
43.3 |
|
ACR50 response, % |
35.7 |
33.9 |
20.4 |
13.3 |
25.3 |
20.0 |
|
ACR70 response, % |
12.5 |
18.6 |
5.3 |
6.7 |
7.6 |
10.6 |
|
ACR-N, mean (SD) |
28.7 (53.6) |
31.9 (47.6) |
-8.9 (126.7) |
11.3 (46.4) |
3.0 (109.8) |
18.8 (47.7) |
|
EULAR [good+moderate], % |
88.5 |
83.9 |
56.0 |
55.6 |
66.0 |
64.9 |
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Baseline DAS28, mean (SD) |
5.5 (1.3) |
6.0 (1.1) |
5.8 (1.2) |
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Change in DAS28, mean (SD) |
-2.0 (1.5) |
-2.1 (1.5) |
-1.2 (1.4) |
-1.3 (1.5) |
-1.4 (1.5) |
-1.5 (1.5) |
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Baseline HAQ, mean (SD) |
1.54 (0.66) |
1.72 (0.56) |
1.66 (0.60) |
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Change in HAQ, mean (SD) |
-0.25 (0.53) |
-0.27 (0.53) |
-0.26 (0.56) |
-0.30 (0.62) |
-0.26 (0.55) |
-0.29 (0.59) |
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aFor ACR measures, patients who discontinued from study prior to Week 52 are imputed as non-responders (n=34), for all other measures the LOCF approach was used. bOnly 1 patient received 60/120/60 mg tabalumab; this patient is included in All Patient data. cTwo patients were excluded from efficacy analyses: 1 patient had no post-baseline efficacy data (60 mg) and was lost to follow-up, and 1 patient was removed due to good clinical practice violations (60/120 mg).
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Table 2. Safety and Pharmacodynamic Outcomes |
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Tabalumab (60 mg) N=60 |
Tabalumab (60/120 mg) n=121 |
All Patients N=182a |
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|
Week 52 |
Week 52 |
Week 52 |
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Discontinued due to AEs, n (%) |
3 (5.0) |
6 (5.0) |
9 (4.9) |
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Deaths, n (%) |
0 (0.0) |
1 (0.8) |
1 (0.5) |
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Serious AEs, n (%) |
4 (6.7) |
16 (13.2) |
21 (11.5) |
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Treatment-emergent AEs, n (%) |
38 (63.3) |
95 (78.5) |
134 (73.6) |
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Infection |
22 (36.7) |
58 (47.9) |
80 (44.0) |
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Infections of the upper respiratory tractb |
16 (25.0) |
32 (25.4) |
47 (25.8) |
|
Urinary tract infection |
2 (3.3) |
13 (10.7) |
15 (8.2) |
|
RA (eg, worsening, flare) |
11 (18.3) |
30 (24.8) |
41 (22.5) |
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Injection-site reaction |
2 (3.3) |
13 (10.7) |
15 (8.2) |
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Injection-site pain |
2 (3.3) |
12 (9.9) |
14 (7.7) |
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aOnly 1 patient received 60/120/60 mg tabalumab; this patient is included in All Patient data. bIncludes MedDRA High Level Terms of Upper Respiratory Tract Infections NEC; Laryngitis, Nasopharyngitis, Pharyngitis, Pharyngotonsillitis, Rhinitis, Sinusitis, Upper Respiratory Tract Infection.
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Disclosure:
M. W. Greenwald,
Eli Lilly and Company ,
2;
L. Szczepanski,
None;
A. C. Kennedy,
None;
C. H. Lee,
Eli Lilly and Company,
1,
Eli Lilly and Company,
3;
E. Polasek,
Eli Lilly and Company,
3;
M. Veenhuizen,
Eli Lilly and Company ,
3,
Eli Lilly and Company,
3;
R. Jones-Taha,
None;
P. Y. Berclaz,
Eli Lilly and Company ,
3.
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