Session Information
Session Type: ACR Late-breaking Abstract Session
Session Time: 9:00AM-11:00AM
Background/Purpose:
Tofacitinib is an oral Janus kinase inhibitor under investigation for treatment of PsA. In this first study of tofacitinib in patients (pts) with active PsA and an inadequate response (IR) to TNF inhibitors (TNFi), efficacy and safety vs placebo (PBO) were evaluated.Methods:
Eligible pts in this 6-month, randomized, PBO-controlled, double-blind, multicenter, Phase 3 study had ≥6 months’ PsA diagnosis, fulfilled ClASsification criteria for Psoriatic ARthritis, had active arthritis (≥3 tender/painful and ≥3 swollen joints) at screening and baseline, active plaque psoriasis at screening, and IR to ≥1 TNFi (discontinuation for inadequate efficacy or an adverse event [AE]). Pts were randomized 2:2:1:1 to tofacitinib 5 mg twice daily (BID; n=132), tofacitinib 10 mg BID (n=132), PBO→tofacitinib 5 mg BID (n=66), or PBO→tofacitinib 10 mg BID (n=65). Pts randomized to PBO advanced (blinded) to tofacitinib 5 or 10 mg BID at Month (M) 3. Ongoing treatment with 1 conventional synthetic DMARD was required. The primary endpoints were ACR20 response rate and change from baseline in Health Assessment Questionnaire Disability Index (ΔHAQ-DI) at M3.Results:
Pt demographics and baseline disease characteristics were broadly similar across groups (Table 1). Of the 395 randomized pts, 394 were treated, 361 (91.6%) completed M3, and 345 (87.6%) completed M6. There were significantly greater improvements in ACR20 response and HAQ-DI for both tofacitinib doses vs PBO at M3; improvements persisted to M6 (Table 2). Tofacitinib 5 and 10 mg BID demonstrated superior ACR20 response vs PBO as early as Week 2 (26.7% and 28.8% vs 13.0%; p≤0.05). Effects on secondary efficacy endpoints were generally consistent with the primary findings (Table 2). Serious AEs and discontinuations due to AEs were low in frequency (Table 3). The most common AEs were upper respiratory tract infection (5.3–10.8% of pts across groups), nasopharyngitis (1.5–10.7%), and headache (4.5–9.1%).Conclusion:
In this first study comprising only TNFi-IR pts with PsA, tofacitinib was superior to PBO in ACR20 response and ΔHAQ-DI at M3, with ACR20 superiority vs PBO as early as Week 2 (first assessment). Secondary endpoints were consistent with the primary analyses. No new safety risks were identified vs previous tofacitinib studies in RA and psoriasis.
| Table 1. Patient demographics and baseline disease characteristics (safety analysis seta) | ||||
|
Placebo (N=131) |
Tofacitinib 5 mg BID (N=131) |
Tofacitinib 10 mg BID (N=132) |
||
| Patient demographics | ||||
| Age, years, mean (SD) |
49.0 (12.6) |
49.5 (12.3) |
51.3 (10.9) |
|
| Female, n (%) |
80 (61.1) |
64 (48.9) |
74 (56.1) |
|
| White, n (%) |
118 (90.1) |
121 (92.4) |
124 (93.9) |
|
| BMI, kg/m2, mean (SD) |
29.5 (5.5) |
30.5 (7.1) |
31.0 (6.7) |
|
| Baseline disease characteristics | ||||
| Duration of PsA, years, mean (SD) |
9.4 (8.1) |
9.6 (7.6) |
9.1 (6.8) |
|
| HAQ-DI score, mean (SD) |
1.3 (0.8) |
1.3 (0.7) |
1.4 (0.6) |
|
| Presence of enthesitis, LEI >0, n (%) |
93 (71.0) |
83 (63.4) |
99 (75.0) |
|
| LEI score,b mean (SD) |
2.8 (1.6) |
3.0 (1.6) |
3.4 (1.8) |
|
| Presence of dactylitis, DSS >0, n (%) |
63 (48.1) |
66 (50.4) |
65 (49.2) |
|
| DSS,b mean (SD) |
6.8 (5.7) |
7.8 (9.9) |
9.5 (8.2) |
|
| PGA of arthritis, VAS (mm), mean (SD) |
53.7 (21.2) |
53.5 (20.9) |
55.8 (20.8) |
|
| PtGA of arthritis, VAS (mm), mean (SD) |
55.8 (23.7) |
57.4 (22.9) |
58.5 (22.3) |
|
| Patient assessment of arthritis pain, VAS (mm), mean (SD) |
54.9 (25.3) |
56.4 (24.1) |
59.5 (22.3) |
|
| Swollen joint count (66), mean (SD) |
10.5 (9.0) |
12.1 (10.6) |
12.8 (11.2) |
|
| Tender/painful joint count (68), mean (SD) |
19.8 (14.9) |
20.5 (13.0) |
25.5 (17.5) |
|
| CRP, mg/L, median (range) |
4.4 (0.2–164.0) |
5.7 (0.2–126.0) |
4.9 (0.2–163.0) |
|
| ≥3% BSA affected by psoriasis, n (%) |
86 (65.6) |
80 (61.1) |
81 (61.4) |
|
| PASI score,c median (range) |
7.1 (1.6–66.0) |
7.6 (0.6–32.2) |
8.8 (0.8–41.6) |
|
| Day 1 oral corticosteroid use, n (%) |
31 (23.7) |
37 (28.2) |
25 (18.9) |
|
| Concomitant csDMARD use up to Month 3, n (%) MTX Otherd |
98 (74.8) 33 (25.2) |
95 (72.5) 36 (27.5) |
89 (67.4) 41 (31.1) |
|
| aAll patients who received ≥1 dose of study medication; bAmong patients with baseline score >0; cAmong patients with baseline BSA ≥3% and PASI >0; dIncludes hydroxychloroquine, chloroquine, leflunomide, and sulfasalazine BID, twice daily; BMI, body mass index; BSA, body surface area; CRP, C-reactive protein; csDMARD, conventional synthetic disease-modifying antirheumatic drug; DSS, Dactylitis Severity Score; HAQ-DI, Health Assessment Questionnaire Disability Index; LEI, Leeds Enthesitis Index; MTX, methotrexate; PASI, Psoriasis Area and Severity Index; PGA, Physician’s Global Assessment; PsA, psoriatic arthritis; PtGA, Patient’s Global Assessment; SD, standard deviation; VAS, visual analog scale | ||||
| Table 2. Efficacy endpoints at Month 3 and Month 6 (full analysis seta) | |||||||
|
Month 3 (active treatment vs placebo) |
Month 6 |
||||||
|
Placebo (N=131) |
Tofacitinib 5 mg BID (N=131) |
Tofacitinib 10 mg BID (N=132) |
Placebo→ tofacitinib 5 mg BID (N=66) |
Placebo→ tofacitinib 10 mg BID (N=65) |
Tofacitinib 5 mg BID (N=131) |
Tofacitinib 10 mg BID (N=132) |
|
| ACR20,b n (%) |
31 (23.7) |
65 (49.6)*** |
62 (47.0)*** |
33 (50.0) |
35 (53.9) |
78 (59.5) |
65 (49.2) |
| ACR50, n (%) |
19 (14.5) |
39 (29.8)* |
37 (28.0)* |
21 (31.8) |
23 (35.4) |
50 (38.2) |
39 (29.6) |
| ACR70, n (%) |
13 (9.9) |
22 (16.8) |
19 (14.4) |
10 (15.2) |
12 (18.5) |
28 (21.4) |
19 (14.4) |
| DHAQ-DI,b LS mean (SE) [N1] |
-0.14 (0.05) [117] |
-0.39 (0.05)*** [124] |
-0.35 (0.05)** [120] |
-0.48 (0.07) [56] |
-0.42 (0.07) [56] |
-0.44 (0.05) [122] |
-0.34 (0.05) [112] |
| PASI75,c n/N (%) |
12/86 (14.0) |
17/80 (21.3) |
35/81 (43.2) *** |
11/42 (26.2) |
14/44 (31.8) |
27/80 (33.8) |
37/81 (45.7) |
| DLEI,d LS mean (SE) [N1] |
-0.5 (0.2) [82] |
-1.3 (0.2)* [79] |
-1.3 (0.2)* [86] |
-1.4 (0.3) [38] |
-1.3 (0.3) [41] |
-1.5 (0.2) [77] |
-1.6 (0.2) [84] |
| DDSS,d LS mean (SE) [N1] |
-1.9 (0.8) [55] |
-5.2 (0.7)* [64] |
-5.4 (0.8)* [58] |
-5.4 (1.3) [25] |
-5.2 (1.3) [26] |
-6.0 (0.8) [61] |
-6.0 (0.9) [55] |
| Nominal *p≤0.05; **p<0.001; ***p<0.0001 vs placebo at Month 3 aAll randomized patients who received ≥1 dose of study medication (N=394); bPrimary study endpoint at Month 3; cIn patients with baseline BSA ≥3% and baseline PASI >0; dIn patients with baseline score >0 Continuous endpoints were analyzed with a mixed model for repeated measures; P values for binary endpoints were based on the normal approximation for the difference in binomial proportions Missing values for ACR20, ACR50, ACR70, and PASI75 were considered as non-response. Missing values for continuous endpoints were not imputed D, change from baseline; ACR, American College of Rheumatology; ACR20/50/70, ACR20%/50%/70% response rate; BID twice daily; BSA, body surface area; DSS, Dactylitis Severity Score; HAQ-DI, Health Assessment Questionnaire Disability Index; LEI, Leeds Enthesitis Index; LS, least squares; N1, number of patients evaluable at a visit of interest; PASI, Psoriasis Area and Severity Index; PASI75, ≥75% improvement from baseline PASI; SE, standard error | |||||||
| Table 3. Safety summary to Month 6 (safety analysis seta; all causality) | |||||
|
Placebo→ tofacitinib 5 mg BID (N=66) |
Placebo→ tofacitinib 10 mg BID (N=65) |
Tofacitinib 5 mg BID (N=131) |
Tofacitinib 10 mg BID (N=132) |
||
| AEs, n (%) |
40 (60.6) |
38 (58.5) |
93 (71.0) |
96 (72.7) |
|
| SAEs, n (%) |
2 (3.0) |
1 (1.5) |
5 (3.8) |
8 (6.1) |
|
| Discontinuation due to AEs, n (%) |
2 (3.0) |
3 (4.6) |
5 (3.8) |
11 (8.3) |
|
| Deaths, n (%) |
0 |
0 |
0 |
0 |
|
| AEs of special interest, n (%) | |||||
| Serious infection |
0 |
0 |
2 (1.5) |
2 (1.5) |
|
| Herpes zoster (all non‑serious) |
0 |
0 |
1 (0.8) |
2 (1.5) |
|
| Opportunistic infectionb |
0 |
0 |
1 (0.8) |
0 |
|
| Malignancyc |
0 |
0 |
0 |
0 |
|
| MACEd |
0 |
0 |
1 (0.8) |
1 (0.8) |
|
| GI perforation |
0 |
0 |
0 |
0 |
|
| aAll patients who received ≥1 dose of study medication; bherpes zoster; cincluding non-melanoma skin cancer; dfor this trial, MACE includes any myocardial infarction, cerebrovascular event (stroke or transient ischemic attack), or cardiovascular death AE, adverse event; BID, twice daily; GI, gastrointestinal; MACE, major adverse cardiovascular event; n, number of patients with event; SAE, serious adverse event | |||||
Disclosure: D. D. Gladman, AbbVie, Amgen, BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB, 2,AbbVie, Amgen, BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB, 5; W. Rigby, Amgen, Pfizer Inc, Roche, 2,BMS, Eli Lilly, Pfizer Inc, Roche, 5; V. F. Azevedo, Pfizer, Abbvie, UCB, Janssen, Bristol Myers-Squibb, 8; F. Behrens, Roche, Pfizer Inc, AbbVie, Celgene, BMS, Novartis, Janssen, 2,Roche, Pfizer Inc, AbbVie, Celgene, BMS, Novartis, Janssen, 5; R. Blanco, None; A. Kaszuba, Novartis, 2,Novartis, Janssen, 5; E. Kudlacz, Pfizer Inc, 1,Pfizer Inc, 3; C. Wang, Pfizer Inc, 1,Pfizer Inc, 3; S. Menon, Pfizer Inc, 1,Pfizer Inc, 3; T. Hendrikx, Pfizer Inc, 1,Pfizer Inc, 3; K. S. Kanik, Pfizer Inc, 1,Pfizer Inc, 3.
To cite this abstract in AMA style:
Gladman DD, Rigby W, Azevedo VF, Behrens F, Blanco R, Kaszuba A, Kudlacz E, Wang C, Menon S, Hendrikx T, Kanik KS. Efficacy and Safety of Tofacitinib, an Oral Janus Kinase Inhibitor, in Patients with Active Psoriatic Arthritis and an Inadequate Response to Tumor Necrosis Factor Inhibitors: OPAL Beyond, a Randomized, Double Blind, Placebo-Controlled, Phase 3 Trial [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/efficacy-and-safety-of-tofacitinib-an-oral-janus-kinase-inhibitor-in-patients-with-active-psoriatic-arthritis-and-an-inadequate-response-to-tumor-necrosis-factor-inhibitors-opal-beyond-a-randomize/. Accessed .« Back to 2016 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-and-safety-of-tofacitinib-an-oral-janus-kinase-inhibitor-in-patients-with-active-psoriatic-arthritis-and-an-inadequate-response-to-tumor-necrosis-factor-inhibitors-opal-beyond-a-randomize/