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. Patients
(pts) with RA often have comorbidities that may affect treatment response. This
post-hoc analysis evaluated whether predefined clinical phenotypes influenced
treatment response, as assessed by different efficacy and safety outcomes.
Methods: Data
from Phase 3 randomized studies of tofacitinib 5 mg BID in RA as monotherapy
(ORAL Solo [NCT00814307], ORAL Start [NCT01039688]) or with background conventional
synthetic DMARDs (csDMARDS; mainly methotrexate [MTX]) (ORAL Scan
[NCT00847613], ORAL Sync [NCT00856544], ORAL Standard [NCT00853385]) were included.
Pts in ORAL Start were MTX-naïve while pts in other studies had an inadequate
response to biologic or csDMARDs, mostly MTX. Efficacy and safety of
tofacitinib was evaluated in subgroups of monotherapy and combination therapy populations
with different high-risk comorbidities: diabetes (history of diabetes and/or treatment
with anti-diabetic medication at baseline [BL]); obesity (BMI ≥30 kg/m2)
and hypertension (history of hypertension
and/or treatment with antihypertensive medication at BL); or obesity and dyslipidemia
(total
cholesterol >2g/L and/or treatment with lipid-lowering medication at BL). Efficacy
outcomes at Month 3 included the proportion of pts achieving
low disease activity (DAS28-4(CRP) ≤3.2); ACR50 response; and mean change
from BL in Health Assessment Questionnaire-Disability Index (HAQ-DI) score. Safety
outcomes included incidences of serious adverse events (SAEs) up to Month 3, discontinuations
due to AEs, and serious infections (SIEs).
Results:
In total, 616 pts received tofacitinib 5
mg BID monotherapy (243 from ORAL Solo and 373 from ORAL Start) and 840 pts received
tofacitinib 5 mg BID with background csDMARDs. Efficacy and safety outcomes by
pt subgroups are presented in the Table.
Tofacitinib 5 mg BID was similarly efficacious across different high-risk clinical
phenotypes.
Incidence
rates for discontinuations due to AEs were numerically higher for the csDMARD
group than the monotherapy group.
Efficacy
and safety outcomes in these subpopulations were
within the ranges of the overall populations for the respective Phase 3
studies.
Conclusion:
These findings suggest that tofacitinib 5 mg BID, when administered as
monotherapy or combination therapy, has a consistent efficacy and safety
profile up to Month 3 in RA pts with different high-risk clinical phenotypes, such
as diabetes. Although these pts are at high risk of further AEs, they appear to
experience a short-term safety profile with tofacitinib similar to the overall clinical
program population. Limitations include the relatively few pts in each clinical
phenotype subgroup, and that the monotherapy group included MTX-naïve pts,
whereas the csDMARD group included DMARD inadequate responders only.
|
Table. Efficacy and safety outcomes at Month 3 |
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|
|
Monotherapy |
Background csDMARDs |
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|
|
Diabetes |
Obese and hypertension |
Obese and dyslipidemia |
Diabetes |
Obese and hypertension |
Obese and dyslipidemia |
|
|
Total, n/N (%) |
Tofacitinib 5 mg BID |
47/616 (7.6) |
77/616 (12.5) |
121/616 (19.6) |
68/840 (8.1) |
108/840 (12.9) |
166/840 (19.8) |
|
Placebo* |
3/122 (2.5) |
23/122 (18.9) |
28/122 (23.0) |
34/427 (8.0) |
45/427 (10.5) |
83/427 (19.4) |
|
|
DAS28-4(CRP) ≤3.2 n/N (%) [CI] |
Tofacitinib 5 mg BID |
14/43 (32.6) [19.1, 48.5] |
24/70 (34.3) [23.4, 46.6] |
37/113 (32.7) [24.2, 42.2] |
18/64 (28.1) [17.6, 40.8] |
29/99 (29.3) [20.6, 39.3] |
37/151 (24.5) [17.9, 32.2] |
|
Placebo* |
0/2 |
2/20 (10.0) [1.2, 31.7) |
4/26 (15.4) [4.4, 34.9] |
2/31 (6.5) [0.8, 21.4] |
3/38 (7.9) [1.7, 21.4] |
2/76 (2.6) [0.3, 9.2] |
|
|
ACR50 response n/N (%) [CI] |
Tofacitinib 5 mg BID |
19/43 (44.2) [29.1, 60.1] |
24/71 (33.8) [23.0, 46.0] |
39/114 (34.2) [25.6, 43.7] |
21/64 (32.8) [21.6, 45.7] |
28/99 (28.3) [19.7, 38.2] |
40/152 (26.3) [19.5, 34.1] |
|
Placebo* |
1/2 (50.0) [1.3, 98.7] |
4/21 (19.1) [5.5, 41.9] |
7/27 (25.9) [11.1, 46.3] |
4/31 (12.9) [3.6, 29.8] |
2/38 (5.3) [0.6, 17.8] |
6/76 (7.9) [3.0, 16.4] |
|
|
HAQ-DI, mean change from BL (SD) |
Tofacitinib 5 mg BID |
-0.6 (0.6) |
-0.6 (0.7) |
-0.5 (0.7) |
-0.5 (0.6) |
-0.3 (0.5) |
-0.4 (0.5) |
|
Placebo* |
-0.3 (0.7) |
-0.2 (0.7) |
-0.4 (0.7) |
-0.3 (0.7) |
-0.3 (0.5) |
-0.2 (0.5) |
|
|
Discont. due to AEs, IR (95% CI) |
Tofacitinib 5 mg BID |
8.9 (3.4, 23.8) |
1.2 (0.2, 8.6) |
3.4 (1.4, 8.2) |
14.3 (7.9, 25.7) |
13.5 (8.1, 22.3) |
12.3 (8.1, 18.7) |
|
Placebo* |
0 |
18.9 (2.7, 134.0) |
0 |
0 |
7.3 (1.0, 51.5) |
3.7 (0.5, 25.9) |
|
|
SAEs, n/N (%) |
Tofacitinib 5 mg BID |
1/47 (2.1) |
2/77 (2.6) |
2/121 (1.7) |
5/68 (7.4) |
7/108 (6.5) |
8/166 (4.8) |
|
Placebo* |
1/3 (33.3) |
2/23 (8.7) |
2/28 (7.1) |
0/34 |
0/45 |
0/83 |
|
|
SIEs, IR (95% CI) |
Tofacitinib 5 mg BID |
6.8 (2.2, 21.1) |
0 |
1.4 (0.3, 5.5) |
3.9 (1.2, 12.0) |
6.3 (3.0, 13.2) |
4.5 (2.2, 8.9) |
|
Placebo* |
0 |
0 |
0 |
9.2 (1.3, 65.6) |
0 |
0 |
|
|
IR, incidence rate: pts with events/100 pt-years *For monotherapy studies, only ORAL Solo had a placebo arm |
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To cite this abstract in AMA style:
Curtis JR, Dikranian A, Mendelsohn A, Soma K, Fan H, Nduaka C. Consistency of Treatment Effects Across Different High-Risk Clinical Phenotypes in the Tofacitinib Clinical Program [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/consistency-of-treatment-effects-across-different-high-risk-clinical-phenotypes-in-the-tofacitinib-clinical-program/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/consistency-of-treatment-effects-across-different-high-risk-clinical-phenotypes-in-the-tofacitinib-clinical-program/