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:
Tofacitinib is an oral Janus kinase inhibitor
for the treatment of RA. This post-hoc pooled analysis was designed to assess
the efficacy and safety of tofacitinib, as monotherapy or combination therapy
with nonbiologic DMARDs, in Latin American (LA) patients with an inadequate
response to prior DMARDs.
Methods:
Phase 3 data were pooled from LA patients receiving
tofacitinib 5 or 10 mg BID or placebo as monotherapy (ORAL Solo
[NCT00814307]) or combination therapy (ORAL Scan [NCT00847613], ORAL Sync
[NCT00856544] and ORAL Standard [NCT00853385]). Patients included in the
analysis were from Brazil, Dominican Republic, Colombia, Mexico, Chile, Peru,
Argentina, Venezuela and Costa Rica. Efficacy outcomes assessed at 3 months
were ACR20, 50 and 70 responses, and the health assessment questionnaire –
disability index (HAQ-DI). Adverse events (AE) and clinical laboratory
parameters were also assessed.
Results:
451 patients were included in the pooled
analysis with a mean age (range) of 49.2 (18-75) years in the combination
therapy arm and 50.4 (22-77) years for monotherapy. Tofacitinib
5 and 10 mg BID as monotherapy or combination therapy had higher ACR20, 50 and
70 response rates than placebo, with similar response rates between monotherapy
and combination therapy for both doses of tofacitinib (Table). Mean change from
baseline in HAQ-DI score was similar for monotherapy and combination therapy
with either dose. Adverse events occurred more
frequently with tofacitinib 5 and 10 mg BID compared with placebo, and
numerically more events with combination therapy were noted compared with
monotherapy in some parameters (Table). Seventeen tofacitinib‑treated patients
withdrew due to adverse events (monotherapy, 4; combination, 13), and four
patients withdrew due to infection (monotherapy, 1; combination, 3). Patients receiving
combination therapy were more likely to develop elevations in liver enzymes. No
patients developed severe neutropenia or lymphopenia, with either monotherapy
or combination therapy.
Conclusion:
In this short-term post-hoc analysis of
pooled, Phase 3 data from LA patients with RA, tofacitinib demonstrated similar
efficacy as monotherapy or combination therapy and patients on tofacitinib
monotherapy appeared to have fewer discontinuations due to adverse events and fewer
elevations in liver enzymes compared with combination therapy over Months 0-3. These
data are consistent with data from the global population of tofacitinib-treated
patients.1
Reference:
1. Keystone et al. Ann Rheum Dis.
2013;72(S3):242.
|
Table. Efficacy and Safety Outcomes Over 3 Months |
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|
Parameter |
Monotherapy |
Combination |
|||||
|
|
Tofacitinib 5 mg BID
N=62 |
Tofacitinib 10 mg BID
N=68 |
Placebo
N=36 |
Tofacitinib 5 mg BID
N = 118 |
Tofacitinib 10 mg BID
N=112 |
Placebo
N=55 |
|
|
ACR20 response rate, n (%) |
43 (69.4) |
53 (81.5) |
12 (37.5) |
76 (70.4) |
76 (73.8) |
16 (33.3) |
|
|
ACR50 response rate, n (%) |
29 (46.8) |
30 (46.2) |
6 (18.8) |
51 (47.2) |
54 (52.4) |
9 (18.8) |
|
|
ACR70 response rate, n (%) |
12 (19.4) |
13 (20.0) |
4 (12.5) |
19 (17.6) |
26 (25.2) |
1 (2.1) |
|
|
HAQ-DI, mean change from baseline (SD) |
-0.58 (0.70) |
-0.68 (0.63) |
-0.26 (0.58) |
-0.66 (0.67) |
-0.82 (0.63) |
-0.32 (0.54) |
|
|
AEs, n (%) |
46 (74.2) |
56 (82.4) |
27 (75.0) |
100 (84.7) |
97 (86.6) |
39 (70.9) |
|
|
Discontinuations due to AEs, n (%) |
2 (3.2) |
2 (2.9) |
1 (2.8) |
5 (4.2) |
8 (7.1) |
2 (3.6) |
|
|
Discontinuation due to infection, n |
0 |
1 |
0 |
2 |
1 |
0 |
|
|
Serious infection, n (%) |
0 |
1 (1.5) |
0 |
2 (1.7) |
3 (2.7) |
0 |
|
|
Neutropenia <500cells/mm3, n |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
Lymphopenia <500 cells/mm3, n |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
AST, n (%) |
|
|
|
|
|
|
|
|
|
>1 ULN |
7 (11.3) |
7 (10.3) |
0 |
21 (17.8) |
24 (22.0) |
5 (9.1) |
|
|
>2 ULN |
2 (3.2) |
0 |
0 |
0 |
2 (1.8) |
0 |
|
|
>3 ULN |
0 |
0 |
0 |
0 |
0 |
0 |
|
ALT, n (%) |
|
|
|
|
|
|
|
|
|
>1 ULN |
7 (11.3) |
6 (8.8) |
1 (2.8) |
28 (23.7) |
21 (19.3) |
5 (9.1) |
|
|
>2 ULN |
2 (3.2) |
2 (2.9) |
0 |
2 (1.7) |
5 (4.6) |
0 |
|
|
>3 ULN |
0 |
0 |
0 |
0 |
2 (1.83) |
0 |
|
LDL, mean mg/dL |
|
|
|
|
|
|
|
|
|
Baseline |
107.82 |
107.85 |
108.15 |
107.21 |
108.27 |
119.71 |
|
|
Month 3 |
124.00 |
127.33 |
111.90 |
125.03 |
126.87 |
115.91 |
|
HDL, mean mg/dL |
|
|
|
|
|
|
|
|
|
Baseline |
59.52 |
59.90 |
59.28 |
57.29 |
55.95 |
56.31 |
|
|
Month 3 |
63.27 |
65.98 |
52.91 |
58.76 |
60.87 |
52.38 |
|
All data are at 3 months unless otherwise stated. ACR, American College of Rheumatology response rate; AE, adverse event; ALT, alanine transaminase; AST, aspartate aminotransferase; HAQ-DI, health assessment questionnaire – disability index; HDL, high density lipoprotein; LDL, low density lipoprotein; ULN, upper limit of normal |
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To cite this abstract in AMA style:
Zerbini C, Radominski S, Cardiel MH, Castañeda O, Romero F, Citera G, Neira O, Ponce de Leon D, Hoffman E, Rojo R. Efficacy and Safety of Tofacitinib Monotherapy Versus Combination Therapy in a Latin American Subpopulation of Patients with Rheumatoid Arthritis: A Pooled Phase 3 Analysis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/efficacy-and-safety-of-tofacitinib-monotherapy-versus-combination-therapy-in-a-latin-american-subpopulation-of-patients-with-rheumatoid-arthritis-a-pooled-phase-3-analysis/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-and-safety-of-tofacitinib-monotherapy-versus-combination-therapy-in-a-latin-american-subpopulation-of-patients-with-rheumatoid-arthritis-a-pooled-phase-3-analysis/