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: Disease Activity, Health Assessment Questionnaire, patient-reported outcome measures, rheumatoid arthritis, treatment and tofacitinib

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
		1^st Outcome
2^nd Outcome (% achieving a response that were also responders for the 1^st 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
		1^st Outcome
2^nd Outcome (% achieving a response that were also responders for the 1^st 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,

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,

B. Wilkinson,

Pfizer Inc,

K. Kwok,

Pfizer Inc,

E. Bananis,

Pfizer Inc,

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