Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Here we compare the efficacy and safety of tofacitinib 5 mg and 10 mg twice daily (BID) vs placebo (PBO) in patients (pts) who had an inadequate response (IR) to nonbiologic/conventional synthetic DMARDs only (csDMARDs; biologic-naïve) and pts with an IR to previous anti- TNF drugs or other biologic DMARDs (biologic-IR pts).
Methods: Efficacy comparisons were performed on pooled data from 4 Phase (Ph) 2 and 5 Ph 3 randomized, controlled studies of tofacitinib in RA pts. Pts received tofacitinib 5 mg or 10 mg BID or PBO as monotherapy, or with background MTX or other csDMARDs. In this analysis, efficacy in biologic‑naïve and biologic‑IR subpopulations was assessed by American College of Rheumatology (ACR) 20/50/70, disease activity score (DAS)28‑4(ESR [erythrocyte sedimentation rate]), Health Assessment Questionnaire-Disability Index (HAQ-DI), Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI). Safety was assessed in pooled Ph 3 pts from 5 studies.
Results: A total of 1071, 1090 and 651 biologic-naïve pts were randomized to tofacitinib 5 mg BID, 10 mg BID and PBO, respectively. For biologic-IR pts, 259, 253, and 193 were randomized to tofacitinib 5mg BID, 10 mg BID and PBO, respectively. Baseline demographics and disease characteristics were similar between tofacitinib and PBO groups within subpopulations. Biologic-IR pts were heavier, with a higher proportion of white pts, had longer disease duration and had slightly greater disease activity at baseline compared with biologic‑naïve pts. In both biologic-naïve and biologic-IR pts in the pooled Ph 2 and 3 studies, clinical response was significantly greater for tofacitinib 5 and 10 mg BID vs PBO; significantly more pts achieved low disease activity and remission with both tofacitinib doses vs PBO by DAS28-4(ESR), SDAI or CDAI (Table 1). Clinical response appeared numerically greater with biologic-naïve vs biologic-IR pts. Rates of safety events of special interest in pooled Ph 3 studies were generally similar between tofacitinib doses and subpopulations (Table 2). Confidence intervals (CI) for safety events were wide and overlapping for all events and treatment groups due to the limited sample size in PBO and biologic-IR groups.
Conclusion: Tofacitinib reduced signs and symptoms of RA in pts who were biologic-naïve and biologic-IR. Tofacitinib had a numerically greater clinical response in the biologic‑naïve population compared with the biologic-IR population. The safety profile appeared similar between the pt subpopulations in Ph 3 studies.
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Table 1. Efficacy responses at Month 3 (pooled Ph 2 and Ph 3 studies) within each subpopulation. All measures were significantly improved with tofacitinib 5 mg or 10 mg BID vs PBO (p<0.05) |
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Biologic-naïve |
Biologic-IR |
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|
Parameter |
Tofacitinib 5 mg BID N=1046 |
Tofacitinib 10 mg BID N=1068 |
PBO N=640 |
Tofacitinib 5 mg BID N=258 |
Tofacitinib 10 mg BID N=251 |
PBO N=191 |
|
ACR20 / 50 / 70 (%) |
60.3 / 32.7 / 12.9 |
66.2 / 36.6 / 18.4 |
26.6 / 9.7 / 2.8 |
43.4 / 24.4 / 9.7 |
51.8 / 27.9 / 12.4 |
24.6 / 10.5 / 3.1 |
|
CDAI ≤10* / ≤2.8† (%) |
32.4 / 6.4 |
39.9 / 9.0 |
14.4 / 0.7 |
29.5 / 5.9 |
35.9 / 6.5 |
14.4 / 1.2 |
|
SDAI ≤11* / ≤3.3† (%) |
34.5 / 6.3 |
41.1 / 9.3 |
14.1 / 0.7 |
29.8 / 6.8 |
38.3 / 8.3 |
13.8 / 0.6 |
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DAS28-4(ESR) ≤3.2* / <2.6† (%) |
16.6 / 7.3 |
22.9 / 11.4 |
4.5 / 2.3 |
12.7 / 6.6 |
17.8 / 8.4 |
5.1 / 2.3 |
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LS mean change in DAS28-4(ESR) |
-1.90 |
-2.12 |
-0.79 |
-1.62 |
-1.98 |
-0.67 |
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HAQ-DI ≤0.5 (%) |
40.4 |
46.2 |
18.1 |
31.0 |
39.2 |
20.1 |
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LS mean change from baseline in HAQ-DI |
-0.46 |
-0.54 |
-0.14 |
-0.31 |
-0.42 |
-0.09 |
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*Low disease activity †Disease remission Ns represent the numbers of subjects with available ACR data at Month 3 ACR, American College of Rheumatology criteria; BID, twice daily; CDAI, Clinical Disease Activity Index; DAS, disease activity score; ESR, erythrocyte sedimentation rate; HAQ-DI, Health Assessment Questionnaire-Disability Index; IR, inadequate responders; LS, least squares; PBO, placebo; Ph, Phase; SDAI, Simplified Disease Activity Index |
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Table 2. Incidence rates (95% CI) of safety events in Ph 3 studies |
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Biologic-naïve Incidence rate, per 100 pt-yr (95% CI) (number of pts with event) |
Biologic-IR Incidence rate, per 100 pt-yr (95% CI) (number of pts with event) |
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Tofacitinib 5 mg BID N=893 Pt-yr=885.5 |
Tofacitinib 10 mg BID N=898 Pt-yr=917.4 |
PBO N=465 Pt-yr=149.5 |
Tofacitinib 5 mg BID N=247 Pt-yr=170.5 |
Tofacitinib 10 mg BID N=241 Pt-yr=154.8 |
PBO N=181 Pt-yr=42.5 |
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Serious adverse events |
12.2 (103) |
9.5 (85) |
15.0 (22) |
13.0 (21) |
11.3 (17) |
19.0 (8) |
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All-cause mortality* |
0.6 (5) |
0.4 (4) |
0.7 (1) |
1.2 (2) |
0 |
0 |
|
Adjudicated MACE |
0.6 (5) |
0.8 (7) |
1.3 (2) |
1.2 (2) |
0.6 (1) |
0 |
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Malignancies excluding NMSC |
0.6 (5) |
0.8 (7) |
0 |
1.2 (2) |
1.9 (3) |
0 |
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Serious infection events |
3.4 (30) |
3.5 (32) |
2.0 (3) |
2.3 (4) |
3.2 (5) |
0 |
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*30-day rule – deaths occurring within 30 days of the last dose BID, twice daily; CI, confidence interval; IR, inadequate responders; MACE, major adverse cardiac events; NMSC, non-melanoma skin cancer; PBO, placebo; pt-yr, patient-years of drug exposure |
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Disclosure:
C. Charles-Schoeman,
Pfizer Inc,
2,
Pfizer Inc,
5;
G. Burmester,
Pfizer Inc,
8,
Pfizer Inc,
2,
Pfizer Inc,
5;
P. Nash,
Pfizer Inc,
2,
Pfizer Inc,
5;
C. A. F. Zerbini,
Pfizer Inc,
2,
Pfizer Inc,
5;
S. Anway,
Pfizer Inc,
3;
K. Kwok,
Pfizer Inc,
1,
Pfizer Inc,
3;
T. Hendrikx,
Pfizer Inc,
3;
E. Bananis,
Pfizer Inc,
3;
R. Fleischmann,
Pfizer Inc,
2,
Pfizer Inc,
5.
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