Time to Response for Clinical and Patient-Reported Outcomes in Patients With Psoriatic Arthritis Treated With Tofacitinib, Adalimumab, or Placebo

Dafna D. Gladman; Laura C. Coates; Joseph Wu; Lara Fallon; Elizabeth D. Bacci; Joseph C. Cappelleri; Andrew G. Bushmakin; Philip S. Helliwell

Disclosures

Arthritis Res Ther. 2022;24(40)

Abstract and Introduction

Abstract

Background: This study examined the time to clinically meaningful response in patients with active psoriatic arthritis treated with tofacitinib, adalimumab, or placebo switching to tofacitinib.

Methods: Data were from two phase 3 studies, OPAL Broaden (12 months) and OPAL Beyond (6 months). Patients received tofacitinib 5 or 10 mg twice daily (BID), adalimumab 40 mg once every 2 weeks (OPAL Broaden only), or placebo switching to tofacitinib 5 or 10 mg BID at month 3. Baseline to initial response time was according to pre-defined clinically meaningful criteria on Health Assessment Questionnaire-Disability Index (HAQ-DI; ≥ 0.35-point improvement), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F; ≥ 4-point improvement), Psoriatic Arthritis Disease Activity Score (PASDAS; post-baseline score ≤ 3.2 and > 1.6-point improvement from baseline), and minimal disease activity (MDA; meeting at least 5 of 7 criteria) composite.

Results: In OPAL Broaden, median time to initial HAQ-DI score response was 29, 53, and 30 days in patients treated with tofacitinib 5 mg BID, tofacitinib 10 mg BID, or adalimumab, compared with 162 and 112 days in patients treated with placebo switching to tofacitinib 5 or 10 mg BID at month 3, respectively. Across studies, median time to initial FACIT-F total score response was shorter in patients receiving tofacitinib 5 mg BID (31 days) vs other groups (84–92 days). Median time to initial response was approximately 11 (MDA)/6–9 months (PASDAS) in tofacitinib/adalimumab groups in OPAL Broaden.

Conclusion: This analysis demonstrates tofacitinib's efficacy on most patient-reported and clinical endpoints over time and shows a shorter time to initial, clinically meaningful response in patients receiving tofacitinib vs patients switching from placebo to tofacitinib.

Trial registration: ClinicalTrials.gov, NCT01877668. Registered June 12, 2013. ClinicalTrials.gov, NCT01882439. Registered June 18, 2013.

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Arthritis Res Ther. 2022;24(40) © 2022 BioMed Central, Ltd.
Copyright to this article is held by the author(s), licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original citation.

Table 1. Time to initial response for outcomes in OPAL Broaden and Beyond (FAS)
Response Treatment sequence	OPAL Broaden				OPAL Beyond
	Responders		Days to response		Responders		Days to response
	N at baseline	Responders (up to month 12)	25th percentile (95% CI)	Median (95% CI)	N at baseline	Responders (up to month 6)	25th percentile (95% CI)	Median (95% CI)
HAQ-DI score response^a
Tofacitinib 5 mg BID	96	84	15.0 (15.0–16.0)	30.0 (27.0–57.0)	116	88	16.0 (15.0–20.0)	37.0 (29.0–61.0)
Tofacitinib 10 mg BID	92	71	16.0 (15.0–27.0)	53.5 (29.0–90.0)	123	80	16.0 (15.0–29.0)	64.0 (57.0–113.0)
ADA 40 mg SC Q2W	96	73	15.0 (15.0–27.0)	29.0 (29.0–57.0)	–	–	–	–
PBO → tofacitinib 5 mg BID	48	30	55.0 (28.0–113.0)	162.0 (85.0–NE)	57	40	16.0 (15.0–57.0)	85.0 (57.0–169.0)
PBO → tofacitinib 10 mg BID	46	36	29.0 (16.0–60.0)	112.0 (57.0–169.0)	59	38	30.0 (17.0–84.0)	113.0 (84.0–169.0)
p value				0.0031**				0.1458
FACIT-F total score response^b
Tofacitinib 5 mg BID	107	87	29.0 (NE–NE)	31.0 (29.0–43.0)	130	98	29.0 (NE–NE)	31.0 (30.0–84.0)
Tofacitinib 10 mg BID	104	84	29.0 (29.0–30.0)	85.0 (34.0–92.0)	132	91	29.0 (NE–NE)	84.0 (32.0–91.0)
ADA 40 mg SC Q2W	106	83	29.0 (29.0–30.0)	85.0 (61.0–92.0)	–	–	–	–
PBO → tofacitinib 5 mg BID	52	42	30.5 (29.0–85.0)	86.0 (85.0–169.0)	66	49	29.0 (29.0–34.0)	85.0 (35.0–164.0)
PBO → tofacitinib 10 mg BID	53	41	29.5 (29.0–33.0)	85.0 (31.0–170.0)	65	41	29.0 (29.0–44.0)	92.0 (81.0–175.0)
p value				0.4136				0.1164
MDA response^c
Tofacitinib 5 mg BID	107	55	85.0 (85.0–253.0)	337.0 (256.0–NE)	131	46	92.0 (85.0–169.0)	NE (NE–NE)
Tofacitinib 10 mg BID	104	54	86.0 (85.0–168.0)	337.0 (171.0–NE)	132	39	96.0 (85.0–NE)	NE (NE–NE)
ADA 40 mg SC Q2W	106	53	86.0 (83.0–169.0)	339.0 (171.0–NE)	–	–	–	–
PBO → tofacitinib 5 mg BID	52	21	251.0 (169.0–339.0)	342.0 (337.0–NE)	66	17	167.0 (86.0–189.0)	189.0 (NE–NE)
PBO → tofacitinib 10 mg BID	53	25	169.0 (168.0–241.0)	338.0 (176.0–NE)	65	21	169.0 (162.0–176.0)	176.0 (174.0–NE)
p value				0.5962				0.6995
PASDAS score response^d
5 mg BID Tofacitinib	107	67	90.0 (84.0–170.0)	253.0 (174.0–335.0)	123	49	85.0 (83.0–167.0)	NE (NE–NE)
Tofacitinib 10 mg BID	103	67	85.0 (83.0–88.0)	176.0 (166.0–258.0)	129	51	86.0 (85.0–168.0)	182.0 (169.0–NE)
ADA 40 mg SC Q2W	104	59	87.0 (85.0–169.0)	253.0 (169.0–NE)	–	–	–	–
PBO → tofacitinib 5 mg BID	52	24	170.0 (166.0–253.0)	344.0 (251.0–NE)	63	22	168.0 (85.0–173.0)	189.0 (169.0–189.0)
PBO → tofacitinib 10 mg BID	52	31	169.0 (169.0–175.0)	241.0 (170.0–323.0)	65	28	169.0 (163.0–169.0)	173.0 (169.0–190.0)
p value				0.2118				0.9613

Log-rank (Mantel–Haenszel) tests comparing Kaplan–Meier curves across treatments; p value based on chi-square test with degrees of freedom = number of treatments – 1; **p ≤ 0.01
PBO → tofacitinib 5 or 10 mg BID groups refers to blinded placebo treatment to month 3 followed by blinded switching to tofacitinib 5 or 10 mg BID
^aHAQ-DI ≥ 0.35-point improvement from baseline (analyzed for patients with baseline HAQ-DI ≥ 0.35)
^bFACIT-F total score ≥ 4-point improvement from baseline
^cMDA yes/no composite response (meeting at least 5 of 7 criteria)
^dPASDAS post-baseline score of ≤ 3.2 and > 1.6-point improvement from baseline (analyzed for patients with baseline PASDAS > 3.2)
Abbreviations: ADA adalimumab, BID twice daily, CI confidence interval, FACIT-F Functional Assessment of Chronic Illness Therapy-Fatigue, FAS full analysis set, HAQ-DI Health Assessment Questionnaire-Disability Index, MDA minimal disease activity, NE not estimable, PASDAS Psoriatic Arthritis Disease Activity Score, PBO placebo, Q2W once every 2 weeks, SC subcutaneous