Improvement in Patient-Reported Outcomes and Work Productivity Following 3-Year Ustekinumab or Tumour Necrosis Factor Inhibitor Treatment in Patients With Psoriatic Arthritis

Results From the PsABio Real-World Study

Laure Gossec; Stefan Siebert; Paul Bergmans; Kurt de Vlam; Elisa Gremese; Beatríz Joven-Ibáñez; Tatiana V. Korotaeva; Frederic Lavie; Wim Noël; Michael T. Nurmohamed; Petros P. Sfikakis; Mohamed Sharaf; Elke Theander; Josef S. Smolen

Disclosures

Arthritis Res Ther. 2023;25(109)

Abstract and Introduction

Abstract

Background: To evaluate the real-world effect of the IL-12/23 inhibitor ustekinumab or of a tumour necrosis factor inhibitor (TNFi) on patient-reported outcomes (PRO) and their association with effectiveness endpoints in psoriatic arthritis (PsA) patients over 3 years.

Methods: In PsABio (NCT02627768), a prospective, observational study, patients with PsA that were prescribed first- to third-line ustekinumab or a TNFi, and remained on that drug for 3 years, were analysed for change in baseline in PROs (EuroQol-5 dimensions health state VAS [EQ-5D VAS], 12-item Psoriatic Arthritis Impact of Disease questionnaire [PsAID-12; range 0–10], Work Productivity and Activity Impairment for Psoriatic Arthritis questionnaire [WPAI; results expressed as a percentage for each domain]), and the association between PROs and WPAI with effectiveness endpoints, clinical disease activity index for psoriatic arthritis (cDAPSA), low disease activity (LDA)/remission, minimal disease activity (MDA) and very low disease activity (VLDA).

Results: In 437 patients (mean age 49.1 years, 47.8% female), at 3 years, ustekinumab and TNFi treatment led to comparable improvements in EQ-5D VAS; mean change from baseline (95% confidence intervals [CI]) was 11.0 (6.5; 15.4) and 18.9 (14.0; 23.9), respectively. Both groups improved PsAID-12 after 3 years; mean change from baseline (95% CI) was −2.9 (−3.2; −2.5) and −3.5 (−3.9; −3.2), respectively. At baseline, due to their PsA, TNFi-treated patients had lower work productivity compared to ustekinumab-treated patients; mean productivity reduction (95% CI) was 58.8 [52.4; 65.2] and 43.3 [35.6; 51.1]. Over 3 years, TNFi-treated patients had a greater improvement in work productivity compared to ustekinumab-treated patients, ultimately leaving work productivity to be comparable between groups; mean improvement (95% CI) was 44.5% (38.4; 50.6) and 24.9% (15.8; 34.0), respectively. A similar trend was observed in activity impairment. Patients in both treatment groups who achieved effectiveness endpoints, cDAPSA LDA/remission, MDA, and VLDA had greater improvement in PROs and WPAI than patients who did not achieve these endpoints.

Conclusions: At 3 years, improvements in PROs following ustekinumab or TNFi treatment were generally comparable; however, TNFi-treated patients achieved a greater improvement in work productivity, although this group started from a lower baseline. Achievement of effectiveness endpoints, independent of treatment group, also improved PROs.

Trial registration: ClinicalTrials.gov, NCT02627768. Registered on 11 December 2015

Introduction

Psoriatic arthritis (PsA) is a chronic, systemic inflammatory arthritis that affects approximately 30% of people with psoriasis, typically presenting equally in men and women between 30 and 60 years of age.^[1,2] People with PsA are commonly burdened by pain, stiffness, swollen joints, psoriasis, and psychosocial disorders, which negatively affect health-related quality of life (HRQoL).^[3] Patients with PsA suffer from sleep problems, depression, mood/behavioural changes, and reduced work productivity.^[3,4] Moreover, chronic widespread pain has a negative impact on treatment outcomes.^[5] Patients with PsA have reduced HRQoL compared with the general population and have worse quality of life (QoL) than people with psoriasis alone.^[5]

The substantial pain and fatigue experienced by patients with PsA are significantly associated with reduced HRQoL, physical function and work productivity.^[6,7] Therefore, it is important to use patient-reported outcome (PRO) measures, in addition to physician-derived joint count or composite measure assessments, to assess physical, social and psychological functioning from the patient's perspective in order to guide treatment decisions.^[8] The increasing treatment options for PsA include tumour necrosis factor inhibitors (TNFi) and interleukin (IL)-12/IL-23 inhibitors. Ustekinumab is a fully human immunoglobulin G1 monoclonal antibody to the p40 subunit of IL-12 and IL-23 and was the first licensed non-TNFi biologic disease-modifying antirheumatic drug (bDMARD) therapy in psoriasis and PsA.^[9] Additionally, ustekinumab has good efficacy against disease activity in joints and skin as well as a favourable safety profile.^[10–12]

While randomised clinical trials (RCTs) provide evidence on the short-term efficacy and safety of a drug, PsA is a long-term condition; thus, it is important to know the effects PsA treatments have on PROs in real-world settings over longer periods of time. Real-world data provide a greater understanding of treatment effectiveness in a patient population in routine clinical care and are, therefore, meaningful for patients and physicians making treatment decisions.^[12–15] Long-term, prospective, real-world data comparing treatments for PsA with different modes of action are lacking.^[12]

The 6-month, 1-year and 3-year data from the prospective, observational PsABio cohort study of ustekinumab and TNFi treatment in patients with PsA indicated that persistence, effectiveness (as assessed by physician-derived joint count) and safety were generally comparable between the two treatments.^[16–18] PROs reflect important functional outcomes for patients; likewise, work status/employment is essential for many patients, and 20–50% of PsA patients report unemployment due to PsA complications.^[19] Real-world evidence on the long-term improvement of PROs and work disability and their link with effectiveness endpoints, low disease activity (LDA)/remission, minimal disease activity (MDA) and very low disease activity (VLDA) is still needed.

Here, we report the PRO and work productivity/activity impairment data and their association with effectiveness endpoints after 3 years of treatment with either ustekinumab or a TNFi in a real-world setting.

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Abstract and Introduction
Methods
Results
Discussion
Conclusion
References

Table 1. Baseline demographics and clinical characteristics of patients with PsA
	UST (n=219) Mean (SD) [95%CI]/n (%) [95%CI]	TNFi (n=218) Mean (SD) [95%CI]/n (%) [95%CI]
Age, years (SD)	51.5 (13.0) [49.8; 53.2]	46.7 (12.7) [45.0; 48.4]
Male, n (%)	106 (48.4) [41.6; 55.2]	122 (56.0) [49.1; 62.7]
Female, n (%)	113 (51.6%) [44.8; 58.4]	96 (44.0%) [37.3; 50.9]
BMI, kg/m² (SD)	28.9 (6.4) [28.0; 29.8]	27.1 (5.0) [26.5; 27.8]
Time since initial diagnosis, years (SD)	7.7 (8.5) [6.5; 8.8]	6.4 (6.7) [5.5; 7.4]
Line of bDMARD treatment, n (%)
First-line	109 (49.8) [43.0; 56.6]	129 (59.2) [52.3; 65.8]
Second-line	71 (32.4) [26.3; 39.1]	69 (31.7) [25.5; 38.3]
Third-line	39 (17.8) [13.0; 23.5]	20 (9.2) [5.7; 13.8]
Cardiometabolic disease^a, n (%)	95 (43.4) [36.7; 50.2]	74 (33.9) [27.7; 40.6]
PsA characteristics, n (%)
Axial involvement^b	7 (3.2) [1.3; 6.5]	7 (3.2) [1.3; 6.5]
Oligoarticular^c	60 (27.8) [21.9; 34.3]	66 (31.0) [24.8; 37.7]
Polyarticular^d	132 (61.1) [54.3; 67.7]	135 (63.4) [56.5; 69.9]
Dactylitis^e, n (%)	46 (21.3) [16.0; 27.4]	62 (29.1) [23.1; 35.7]
Enthesitis^f, n (%)	109 (50.7) [43.8; 57.6]	106 (48.8) [42.0; 55.7]
BSA, n (%)
Clear/almost clear	43 (21.3) [15.9; 27.6]	58 (29.4) [23.2; 36.3]
<3% but not clear/almost clear	18 (8.9) [5.4; 13.7]	36 (18.3) [13.1; 24.4]
3–10%	72 (35.6) [29.0; 42.7]	72 (36.5) [29.8; 43.7]
>10%	69 (34.2) [27.6; 41.1]	31 (15.7) [10.9; 21.6]
Psoriatic nail lesions^g, n (%)	117 (55.7) [48.7; 62.5]	96 (45.7) [38.8; 52.7]
cDAPSA, n (SD)	30.3 (21.7) [27.3; 33.3]	30.3 (20.8) [27.4; 33.2)
Swollen joint count, n (SD)	6.1 (8.5) [4.9; 7.2]	7.0 (8.7) [5.8; 8.3]
Tender joint count, n (SD)	12.7 (13.6) [10.8; 14.6]	11.8 (11.6) [10.1; 13.4]
CRP, mg/dL (SD)	1.7 (3.8) [1.1; 2.3]	1.4 (1.9) [1.1; 1.6]
FiRST score^h
Total score	3.5 [3.30; 3.68]	3.2 [2.99; 3.36]
Scores ≥5, %	39.0 [34.4; 43.8]	30.1 [25.8; 34.6]

Results reflect assessments for patients still under initial treatment at 3 years. Bold text indicates non-overlapping 95% CI
^aHypertension, myocardial infarction, congestive heart failure, stroke or transient ischemic attack, peripheral vascular disease, hyperlipidaemia, type 1 or 2 diabetes or angina pectoris
^bPure axial PsA is defined as having only axial involvement (presence of axial disease declared by the treating rheumatologist without a requirement for imaging)
^cEither TJC68 and SJC66 are both non-missing and patient has <5 swollen or <5 tender joint counts or, in case TJC68 and/or SJC66 are missing, monoarticular or oligoarticular PsA is indicated by the investigator
^dEither TJC68 and SJC66 are both non-missing and patient has ≥5 swollen and ≥5 tender joint counts or, in case TJC68 and/or SJC66 are missing, polyarticular PsA is indicated by the investigator
^eDactylitis presence detected by assessment of hands and feet
^fEnthesitis presence defined as Leeds Enthesitis Index ≥0
^gNail lesions were evaluated by recording the total number of nails of the hands and feet with PsA involvement
^hBased on the FAS (UST n=458 and TNFi n=471) as data were recorded at baseline only
bDMARD, biologic disease-modifying antirheumatic drug; BMI, body mass index; BSA, body surface area; cDAPSA, Clinical Disease Activity in Psoriatic Arthritis; CI Confidence interval, CRP C-reactive protein, FAS Full analysis set, FiRST Fibromyalgia Rapid Screening Tool, PsA Psoriatic arthritis, SD Standard deviation, SJC66 66 swollen joint count, TJC68 68 tender joint count, TNFi Tumour necrosis factor inhibitor UST, Ustekinumab

Table 2. Observed patient-reported outcomes at baseline and at 36 months
Patient-reported outcomes	UST (n=219) Mean [95%CI]	TNFi (n=218) Mean [95%CI]
EQ-5D health state: VAS score^a
Baseline	55.2 [52.3; 58.0]	51.1 [48.2; 54.0]
36 months	66.2 [62.4; 69.9]	70.0 [66.0; 74.1]
Change from baseline	11.0 [6.5; 15.4]	18.9 [14.0; 23.9]
PsAID-12: overall PsAID^b
Baseline	5.4 [5.1; 5.7]	5.3 [5.0; 5.6]
36 months	2.5 [2.2; 2.8]	1.8 [1.5; 2.0]
Change from baseline	−2.9 [−3.2; −2.5]	−3.5 [−3.9; −3.2]
PsAID-12: pain^c
Baseline	6.0 [5.6; 6.3]	6.1 [5.7; 6.4]
36 months	3.0 [2.7; 3.4]	2.3 [2.0; 2.6]
Change from baseline	−2.9 [−3.3; −2.5]	−3.8 [−4.2; −3.4]
PsAID-12: skin^d
Baseline	6.0 [5.6; 6.4]	4.8 [4.4; 5.2]
36 months	2.1 [1.8; 2.4]	1.6 [1.3; 1.9]
Change from baseline	−3.9 [−4.4; −3.4]	−3.1 [−3.6; −2.7]
WPAI: work time missed (absenteeism)^e, %
Baseline	13.2 [6.8; 19.7]	24.0 [16.4; 31.6]
36 months	1.5 [−0.1; 3.0]	3.2 [0.6; 5.8]
Change from baseline	−11.8 [−18.4; −5.1]	−20.8 [−27.9; −13.6]
WPAI: impairment while working (presenteeism)^f, %
Baseline	37.8 [31.9; 43.7]	51.0 [45.4; 56.6]
36 months	16.3 [12.2; 20.3]	13.7 [10.1; 17.2]
Change from baseline	−21.6 [−28.3; −14.8]	−37.3 [−42.8; −31.8]
WPAI: work productivity loss^g, %
Baseline	43.3 [35.6; 51.1]	58.8 [52.4; 65.2]
36 months	18.4 [13.5; 23.3]	14.3 [10.3; 18.3]
Change from baseline	−24.9 [−34.0; −15.8]	−44.5 [−50.6; −38.4]
WPAI: activity impairment^h, %
Baseline	53.1 [49.2; 57.0]	57.9 [54.2; 61.6]
36 months	25.1 [21.6; 28.6]	17.3 [14.4; 20.1]
Change from baseline	−28.0 [−32.4; −23.5]	−40.7 [−44.5; −36.8]

Results reflect the latest assessments for patients considered as remaining on their initial treatment through 3 years. Bold text indicates non-overlapping 95% CI. Baseline, 36-month and change from baseline values are unadjusted data with LOCF imputation. Only skin and pain domains of PsAID-12 are presented here
^a26 patients from the UST group are missing, and 27 patients from the TNFi group are missing
^b7 patients from the UST group are missing, and 23 patients from the TNFi group are missing
^c7 patients from the UST group are missing, and 22 patients from the TNFi group are missing
^d5 patients from the UST group are missing, and 21 patients from the TNFi group are missing
^e143 patients from the UST group are missing, and 128 patients from the TNFi group are missing
^f123 patients from the UST group are missing, and 117 patients from the TNFi group are missing
^g143 patients from the UST group are missing, and 133 patients from the TNFi group are missing
^h15 patients from the UST group are missing, and 21 patients from the TNFi group are missing
CI, confidence interval; EQ-5D health state VAS, EQ-5D-3L health visual analogue scale, LOCF Last observation carried forward, PsAID-12 The 12-item Psoriatic Arthritis Impact of Disease questionnaire, TNFi Tumour necrosis factor inhibitor, UST Ustekinumab, VAS Visual analogue scale, WPAI Work Productivity and Activity Impairment

Authors and Disclosures

Laure Gossec^1,2*, Stefan Siebert³, Paul Bergmans⁴, Kurt de Vlam⁵, Elisa Gremese⁶, Beatríz Joven-Ibáñez⁷, Tatiana V. Korotaeva⁸, Frederic Lavie⁹, Wim Noël¹⁰, Michael T. Nurmohamed¹¹, Petros P. Sfikakis¹², Mohamed Sharaf¹³, Elke Theander^14,15 and Josef S. Smolen¹⁶

¹Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France. ²Rheumatology Department, Pitié-Salpêtrière Hospital, APHP, 47–83 Boulevard de l'Hôpital, 75013 Paris, France. ³University of Glasgow, Glasgow, UK. ⁴Janssen-Cilag BV, Breda, The Netherlands. ⁵University Hospitals Leuven, Leuven, Belgium. ⁶Fondazione Policlinico A Gemelli-IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy. ⁷University Hospital, 12 de Octubre, Madrid, Spain. ⁸VA Nasonova Research Institute of Rheumatology, Moscow, Russian Federation. ⁹The Janssen Pharmaceutical Companies of Johnson & Johnson, Paris, France. ¹⁰Janssen Pharmaceutica NV, Beerse, Belgium. ¹¹Reade and VU University Medical Center, Amsterdam, The Netherlands. ¹²National and Kapodistrian University of Athens Medical School, Athens, Greece. ¹³Johnson and Johnson MEA, Dubai, United Arab Emirates. ¹⁴Janssen, Solna, Sweden. ¹⁵Present address: Malmö University Hospital, Malmö, Sweden. ¹⁶Medical University of Vienna, Vienna, Austria.

*Correspondence
Laure Gossec laure.gossec@aphp.fr

Authors' contributions
LG, SS, PB, KdV, EG, BJI, TVK, FL, WN, PPS, ET, JSS contributed to conceptualisation of the study; LG, SS, PB, KdV, TVK, FL, WN, MTN, ET contributed to the development of study design, data curation and methodology; PB, KdV, FL, MTN, ET contributed to formal data analysis and validation of results; FL, WN, MS provided funding acquisition and financial support for the project; LG, SS, KdV, EG, BJI, TVK, MTN, PPS, ET conducted the research; EG, FL, MTN, PPS, MS, ET planned, directed and coordinated research activity; KdV, EG, BJI, MTN, PPS provided resources and analysis tools; PB contributed to programming and implementation of computer programs; SS, KdV, EG, FL, WN, MTN, PPS, ET, JSS provided supervision of the research including mentorship; LG, SS, PB, KdV, EG, BJI, TVK, MTN, MS, ET contributed to data visualisation and presentation; LG, PB, EG, WN, MTN, ET contributed to preparing and writing the manuscript. All authors reviewed, provided critical review at each stage, and approved the final version of the manuscript. LG is the guarantor.

Competing interests
LG reports personal fees from Janssen during the conduct of the study, research grants from Amgen, Galapagos, Lilly, Pfizer, Sandoz and Sanofi; and consulting fees from AbbVie, Amgen, BMS, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis and UCB outside the submitted work. SS reports non-financial support from Janssen during the conduct of the study; personal fees from AbbVie, Biogen, Novartis and UCB; grants from Amgen (previously Celgene), Boehringer-Ingelheim and Bristol-Myers-Squibb; grants and personal fees from GlaxoSmithKline, Janssen and Eli Lilly outside the submitted work. PB reports personal fees from Janssen and personal fees from Johnson & Johnson during the conduct of the study. KdV reports personal and consulting fees from Janssen. EG reports payment or honoraria from AbbVie, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Galapagos, GSK, Janssen, Novartis, Pfizer and Sanofi. BJI reports consulting fees from Amgen, Janssen and UCB; and payment or honoraria from AbbVie, Eli Lilly, Janssen, Novartis and UCB. TVK reports consulting/speaker fees from AbbVie, Eli Lilly, Janssen, Novartis, Sandoz, BiOCAD, Pfizer and MCD. FL reports non-financial support from Janssen during the conduct of the study. WN is a full-time employee of and owns stock at Johnson & Johnson. MTN reports grants and non-financial support from Janssen during the conduct of the study; grants and personal fees from AbbVie and Eli Lilly; grants from Amgen, BMS and Pfizer; and grants from Galapagos outside the submitted work. PPS reports non-financial support from Janssen during the conduct of the study; grants and personal fees from AbbVie, Eli Lilly, Novartis and Pfizer; grants from UCB; and personal fees from MSD outside the submitted work. MS is a full-time Johnson & Johnson employee and reports non-financial support from Janssen during the conduct of the study. ET was an employee of Janssen during the conduct of the study and preparation of this paper. JSS received grants to his institution from Abbvie, Astro, AstraZeneca, Janssen, Lilly, Merck Sharpe & Dohme, Pfizer, and Roche and provided expert advice for, or had symposia speaking engagements with, AbbVie, Amgen, AstraZeneca, Astro, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Gilead, ILTOO Pharma, Janssen, Lilly, Merck Sharp & Dohme, Novartis-Sandoz, Pfizer, R-Pharma, Roche, Samsung, Sanofi, and UCB.