ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1634

The Effects of Glucocorticoids on the Efficacy of Tofacitinib As Monotherapy and in Combination Therapy with Nonbiologic Dmards: An Analysis of Data from Six Phase 3 Studies

Roy Fleischmann1, Christina Charles-Schoeman2, Gerd Burmester3, Cristiano Zerbini4, Peter Nash5, Kenneth Kwok6, Koshika Soma7, Alan Mendelsohn8 and Eustratios Bananis8, 1Metroplex Clinical Research Center, Dallas, TX, 2University of California, Los Angeles, CA, 3Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany, 4Centro Paulista de Investigação Clinica, São Paulo, Brazil, 5Nambour Hospital, Sunshine Coast and Department of Medicine, University of Queensland, Queensland, Australia, 6Pfizer Inc, New York, NY, 7Pfizer Inc, Groton, CT, 8Pfizer Inc, Collegeville, PA

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: , ,

Session Information

Date: Monday, November 9, 2015

Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy Poster II

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. Patients with RA often receive concomitant treatment with glucocorticoids (GCs) to control inflammatory symptoms. Therefore, the objective of this analysis was to determine whether the presence or absence of oral GCs has an effect on the efficacy of tofacitinib as monotherapy or in combination with nonbiologic DMARDs, within the RA program.

Methods: Tofacitinib efficacy data were analyzed from six Phase 3 (P3) studies. Data were pooled from four P3 studies in which patients with inadequate response (IR) to MTX, biologic/nonbiologic DMARDs, or TNF inhibitors (TNFi) received tofacitinib in combination with MTX or other nonbiologic DMARDs. Data from two P3 tofacitinib monotherapy studies, ORAL Solo (in DMARD-IR patients) and ORAL Start (in MTX-naïve patients), were analyzed separately. In the P3 tofacitinib clinical program, patients receiving GCs (≤10 mg/day of prednisone or equivalent) prior to enrollment were required to remain on a stable dose throughout the study. The following efficacy endpoints were assessed for patients receiving tofacitinib 5 or 10 mg twice daily, placebo +/- DMARDs or +/- MTX (comparator arms), +/- concomitant GCs: ACR response criteria (ACR20, ACR50, ACR70), Clinical Disease Activity Index (CDAI), disease activity score in 28 joints using the ESR (DAS28-4 [ESR]), and HAQ-disability index (HAQ-DI).

Results: In total, 3200 tofacitinib-treated patients were included in this analysis. 279 (57%) and 354 (46%) tofacitinib-treated patients in the P3 monotherapy studies ORAL Solo and ORAL Start were using concomitant GCs, respectively, as were 1129 (58%) tofacitinib-treated patients in the pooled P3 combination studies. Within each study, baseline demography and disease characteristics were similar regardless of concomitant GC use. The efficacy of tofacitinib, placebo +/- DMARDs or MTX, +/- concomitant GCs at 3 months is presented in the Table. Tofacitinib-treated patients had significantly greater treatment responses compared with the comparator arms for almost all efficacy endpoints. Similar responses were observed with tofacitinib regardless of concomitant GC use.

Conclusion: Tofacitinib was more effective than placebo +/- DMARDs or MTX as monotherapy and combination therapy. As expected, the efficacy of tofacitinib was similar in patients receiving and not receiving concomitant GCs as these patients had active disease in spite of their background GCs. A randomized clinical trial in GC-naïve patients with RA is needed to determine the effect of the addition of GCs on the efficacy of tofacitinib.

 

Table: Efficacy of tofacitinib as monotherapy or combination therapy with or without GCs at 3 months

ORAL Solo (DMARD-IRa)

ORAL Start (MTX-naïve)

 

Pooled data from four

Phase 3 studies of tofacitinib in combination with DMARDsb (DMARD-IRa)

Placebo

(+/- GCs)

(N=70/52)

Tofacitinib

5 mg BID

(+/- GCs)

(N=139/104)

Tofacitinib

10 mg BID

(+/- GCs)

(N=140/105)

MTX

(+/- GCs)

(N=87/99)

Tofacitinib

5 mg BID

(+/- GCs)

(N=181/192)

Tofacitinib

10 mg BID

(+/- GCs)

(N=173/224)

Placebo +  DMARDs

(+/- GCs)

(N=322/237)

Tofacitinib

5 mg BID

(+/- GCs)

(N=579/394)

Tofacitinib

10 mg BID

(+/- GCs)

(N=550/419)

ACR20 (%)

29/24

58*/63*

61*/72*

48/56

71*/69*

75*/80*

29/22

54*/57*

60*/63*

ACR50 (%)

13/12

32*/30*

36*/38*

17/23

38*/42*

46*/53*

9/7

28*/30*

32*/33*

ACR70 (%)

6/6

17*/14

19*/22*

4/7

20*/20*

24*/29*

2/2

10*/11*

15*/15*

CDAI ≤ 10 (LDA) (%)

10/14

28*/32*

30*/38*

15/21

36*/40*

42*/50*

11/8

28*/30*

32*/36*

CDAI ≤ 2.8 (remission) (%)

3/0

6/5*

9/8*

2/4

8*/10

9*/13*

0/1

5*/6*

5*/8*

HAQ-DI improvement ≤ 0.22 (%)

43/40

59*/63*

70*/65*

63/71

78*/76

83*/82*

47/42

63*/64*

70*/68*

HAQ-DI improvement ≤ 0.5 (%)

24/28

47*/45*

54*/43

42/47

65*/62*

73*/71*

27/20

44*/44*

53*/51*

Mean change from baseline in HAQ (LS mean)

-0.2/-0.1

-0.5*/-0.5*

-0.6*/-0.5*

-0.5/-0.5

-0.7*/-0.8*

-0.8*/-0.9*

-0.2/-0.2

-0.4*/-0.5*

-0.5*/-0.5*

Mean change from baseline in DAS28-4 (ESR) (LS mean)

-1.1/-1.1

-1.9*/-2.0*

-2.0*/-2.3*

-1.5/-1.6

-2.3*/-2.5*

-2.5*/-2.7*

-0.8/-0.7

-1.8*/-1.8*

-2.0*/-2.0*

Mean change from baseline in CDAI (LS mean)

-11.5/-12.7

-20.5*/-21.9*

-22.1*/-25.0*

-16.3/-18.1

-22.8*/-24.7*

-24.5*/-26.1*

-9.8/-8.7

-17.8*/-18.2*

-19.8*/-19.9*

aPatients with an IR to DMARDs.

bORAL Scan, ORAL Step, ORAL Sync and ORAL Standard.

*Significant difference from the comparator arm: the 95% CI for the difference from the comparator arm does not cross 0.

N, number of patients randomized and treated; denominators for each outcome at Month 3 are different depending upon the number of patients with evaluable outcomes.

ACR, American College of Rheumatology response criteria; BID, twice daily; CDAI, Clinical Disease Activity Index; CI, confidence interval; DAS28-4, disease activity score in 28 joints; DMARDs, nonbiologic disease-modifying antirheumatic drug; ESR, erythrocyte sedimentation rate; GC, glucocorticoid; HAQ-DI, health assessment questionnaire-disability index; IR, inadequate response; LS, least squares; MTX, methotrexate

 

Disclosure: R. Fleischmann, Pfizer Inc, 2,Pfizer Inc, 5; C. Charles-Schoeman, Pfizer Inc, 2,Pfizer Inc, 5; G. Burmester, Pfizer Inc, 2,Pfizer Inc, 5,Pfizer Inc, 8; C. Zerbini, Pfizer Inc, 2,Pfizer Inc, 5; P. Nash, Pfizer Inc, 2,Pfizer Inc, 5; K. Kwok, Pfizer Inc, 1,Pfizer Inc, 3; K. Soma, Pfizer Inc, 1,Pfizer Inc, 3; A. Mendelsohn, Pfizer Inc, 1,Pfizer Inc, 3; E. Bananis, Pfizer Inc, 1,Pfizer Inc, 3.

To cite this abstract in AMA style:

Fleischmann R, Charles-Schoeman C, Burmester G, Zerbini C, Nash P, Kwok K, Soma K, Mendelsohn A, Bananis E. The Effects of Glucocorticoids on the Efficacy of Tofacitinib As Monotherapy and in Combination Therapy with Nonbiologic Dmards: An Analysis of Data from Six Phase 3 Studies [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/the-effects-of-glucocorticoids-on-the-efficacy-of-tofacitinib-as-monotherapy-and-in-combination-therapy-with-nonbiologic-dmards-an-analysis-of-data-from-six-phase-3-studies/. Accessed .

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