ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2488

Relationship Between Different Clinical Measurements and Patient-Reported Outcomes

Roy Fleischmann1, V Strand2, B Wilkinson3, K Kwok4 and E Bananis3, 1Metroplex Clinical Research Center, University of Texas Southwestern Medical Center, Department of Medicine, Dallas, TX, 2Biopharmaceutical Consultant, Portola Valley, CA, 3Pfizer Inc, Groton, CT, 4Pfizer Inc, New York, NY

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: , , , ,

Session Information

Session Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy: Therapeutic Strategies, Biomarkers and Predictors of Outcomes in Rheumatoid Arthritis

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 relationship between clinical measures and patient-reported outcomes (PROs) in patients (pts) with RA treated with tofacitinib or methotrexate (MTX).

Methods: MTX-naïve pts with RA from a double-blind, parallel group, Phase 3 trial (ORAL Start; NCT01039688) were randomized (2:2:1) and treated with tofacitinib 5 mg twice daily (BID) monotherapy (N=373), tofacitinib 10 mg BID monotherapy (N=397), or MTX titrated from 10 to 20 mg/week (N=186). Clinical measures included: the proportion of pts achieving ACR50 and ACR70 responses, the proportion achieving low disease activity (LDA) measured by Clinical Disease Activity Index (CDAI LDA, CDAI≤10), and Simplified Disease Activity Index (SDAI LDA, SDAI≤11), and the proportion achieving remission (REM) measured by CDAI REM (CDAI≤2.8) and SDAI REM (SDAI≤3.3). PROs included: proportion of pts achieving improvements in physical function measured by the Health Assessment Questionnaire-Disability Index (HAQ‑DI, to normative values <0.5).

Results: At Month 6, a greater proportion of pts achieved ACR responses, LDA, and REM with tofacitinib 5 mg or 10 mg BID than with MTX (Tables). Most pts who achieved LDA and REM by one measure also achieved LDA and REM by other measures (Tables); however, discordance was observed between different measures of LDA and REM, and appeared greater with MTX vs either tofacitinib dose (Tables). As expected there was a high degree of concordance between CDAI LDA and SDAI LDA (Table 1) and CDAI REM and SDAI REM (Table 2). Overall, pts achieving LDA or ACR50 showed less improvement from baseline in patient-reported pain, and patient global assessment of disease compared with tender joints, swollen joints, physician global assessment of disease, and HAQ-DI: pts receiving MTX showed an overall lower improvement in these PROs compared with tofacitinib 5 mg or 10 mg BID. In general, better improvements and consistency in PROs were observed in ACR50 responders compared with measures of LDA. Pts achieving ACR70, CDAI REM, and SDAI REM showed similar improvements across PROs and similarly between MTX and tofacitinib.

Conclusion: A higher proportion of MTX-naïve pts receiving tofacitinib 5 or 10 mg BID achieved a clinical response compared with pts receiving MTX. While most pts achieve similar responses across different clinical measures, many may achieve a response in one measure but not the other. Variability of responses with clinical

 


Table 1. ACR50 and LDA clinical disease activity outcomes at Month 6
  Treatment ACR50 CDAI LDA SDAI LDA HAQ-DI (<0.5)
Overall Responders, n/N (%) Tofacitinib 5 mg BID 171/340 (50) 160/339 (47) 170/338 (50) 151/340 (44)
  Tofacitinib 10 mg BID 226/367 (62) 223/366 (61) 226/366 (62) 197/366 (54)
  Methotrexate 50/158 (32) 54/158 (34) 53/158 (34) 42/158 (27)
n, number of responders; N, number of patients assessed at Month 6
    1st Outcome
2nd Outcome (% achieving a response that were also responders for the 1st outcome) Treatment ACR50 responder CDAI LDA responder (≤10) SDAI LDA responder (≤11) HAQ-DI responder (<0.5)
ACR50 responder, % Tofacitinib 5 mg BID NA 79 78 80
  Tofacitinib 10 mg BID NA 86 85 81
  Methotrexate NA 69 70 60
CDAI LDA responder (≤10), % Tofacitinib 5 mg BID 74 NA 94 70
  Tofacitinib 10 mg BID 85 NA 98 81
  Methotrexate 74 NA 96 67
SDAI LDA responder (≤11), % Tofacitinib 5 mg BID 77 100 NA 72
  Tofacitinib 10 mg BID 85 99 NA 82
  Methotrexate 74 94 NA 62
HAQ-DI (<0.5), % Tofacitinib 5 mg BID 71 66 64 NA
  Tofacitinib 10 mg BID 70 72 71 NA
  Methotrexate 50 52 49 NA
Numbers of patients available for assessment varied between parameters
ACR, American College of Rheumatology; ACR50, ≥50% improvement from baseline in both tender and swollen joint counts and ≥50% improvement in ≥3 of the 5 remaining ACR core set measures (pain, disability, C-reactive protein or erythrocyte sedimentation rate, patient and physician global assessments);  BID, twice daily; CDAI, Clinical Disease Activity Index; HAQ-DI, Health Assessment Questionnaire-Disability Index; LDA low disease activity; NA, not applicable; SDAI, Simplified Disease Activity Index
 
 

Table 2. ACR70 and REM clinical disease activity outcomes at Month 6
  Treatment ACR70 CDAI REM SDAI REM HAQ-DI (<0.5)
Overall Responders, n/N (%) Tofacitinib 5 mg BID 94/340 (28) 44/339 (13) 46/338 (14) 151/340 (44)
  Tofacitinib 10 mg BID 149/367 (41) 79/366 (22) 84/366 (23) 197/366 (54)
  Methotrexate 23/158 (15) 14/158 (9) 15/158 (9) 42/158 (27)
n, number of responders; N, number of patients assessed at Month 6
    1st Outcome
2nd Outcome (% achieving a response that were also responders for the 1st outcome) Treatment ACR70
responder 		CDAI REM responder (≤2.8) SDAI REM responder (≤3.3) HAQ-DI responder (<0.5)
ACR70 responder, % Tofacitinib 5 mg BID NA 82 83 52
  Tofacitinib 10 mg BID NA 94 92 59
  Methotrexate NA 71 73 38
CDAI REM responder (≤2.8), % Tofacitinib 5 mg BID 38 NA 96 26
  Tofacitinib 10 mg BID 50 NA 90 34
  Methotrexate 43 NA 93 24
SDAI REM responder (≤3.3), % Tofacitinib 5 mg BID 40 100 NA 26
  Tofacitinib 10 mg BID 52 96 NA 36
  Methotrexate 48 100 NA 26
HAQ-DI (<0.5), % Tofacitinib 5 mg BID 84 89 87 NA
  Tofacitinib 10 mg BID 79 84 85 NA
  Methotrexate 70 71 73 NA
Numbers of patients available for assessment varied between parameters
ACR, American College of Rheumatology; ACR70, ≥70% improvement from baseline in both tender and swollen joint counts and ≥70% improvement in ≥3 of the 5 remaining ACR core set measures (pain, disability, C-reactive protein or erythrocyte sedimentation rate, patient and physician global assessments);  BID, twice daily; CDAI, Clinical Disease Activity Index; HAQ-DI, Health Assessment Questionnaire-Disability Index; NA, not applicable; REM, remission; SDAI, Simplified Disease Activity Index
 

Disclosure:

R. Fleischmann,

Pfizer Inc,

2,

Pfizer Inc,

5;

V. Strand,

AbbVie, Afferent, Amgen, Biogen Idec, Bioventus, BMS, Carbylan, Celgene, Celltrion, CORRONA, Crescendo, Genentech/Roche, GSK, Hospira, Iroko, Janssen, Lilly, Merck, Novartis, Pfizer Inc, Regeneron, Sanofi, SKK, Takeda, UCB, Vertex,

5;

B. Wilkinson,

Pfizer Inc,

1,

Pfizer Inc,

3;

K. Kwok,

Pfizer Inc,

1,

Pfizer Inc,

3;

E. Bananis,

Pfizer Inc,

1,

Pfizer Inc,

3.

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