Dataset Information

Association between enthesitis/dactylitis resolution and patient-reported outcomes in guselkumab-treated patients with psoriatic arthritis.

ABSTRACT:

Objectives

To evaluate the association between enthesitis resolution (ER) and dactylitis resolution (DR) and meaningful improvements in patient-reported outcomes (PROs) among biologic-naïve patients with PsA receiving guselkumab in the DISCOVER-2 study.

Methods

Enthesitis and dactylitis, characteristic lesions of PsA, were evaluated by independent assessors using the Leeds Enthesitis Index (range, 0-6) and Dactylitis Severity Score (range, 0-60). Proportions of patients with ER or DR (score = 0) among those with score > 0 at baseline were determined at weeks 24, 52, and 100. PROs included: fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-Fatigue]), pain (0-100 visual analog scale), physical function (Health Assessment Questionnaire-Disability Index [HAQ-DI]), and health-related quality of life (36-item Short-Form Health Survey physical/mental component summary [SF-36 PCS/MCS]). Meaningful responses were defined as: improvements of ≥ 4 for FACIT-Fatigue, ≥ 0.35 for HAQ-DI, and ≥ 5 for SF-36 PCS/MCS and absolute scores of ≤ 15 for minimal pain and ≤ 0.5 for normalized HAQ-DI. Associations between ER/DR status and PRO response status were tested using a Chi-square test.

Results

Guselkumab-treated patients with ER were more likely than those without ER to achieve minimal pain (p < 0.001), normalized HAQ-DI (p < 0.001), and PCS response (p < 0.05) at weeks 24, 52, and 100. Patients with DR were more likely than those without DR to achieve FACIT-Fatigue response at week 24 and week 52 (both p ≤ 0.01) and minimal pain at week 24 and normalized HAQ-DI at week 52 (both p ≤ 0.03).

Conclusion

In biologic-naïve patients with active PsA treated with guselkumab, achieving ER or DR was associated with durable improvements in selected PROs, including those of high importance to patients.

Trial registration

ClinicalTrials.gov ( https://clinicaltrials.gov ) NCT03158285; Registered: May 16, 2017. Key Points • At week 100, 65% and 76% of guselkumab-treated patients achieved enthesitis and dactylitis resolution (ER/DR). • Achieving ER was associated with achieving DR and vice versa through the end of study. • Achieving ER or DR was associated with durable and meaningful improvements in selected patient-reported outcomes.

SUBMITTER: Rahman P

PROVIDER: S-EPMC11018666 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association between enthesitis/dactylitis resolution and patient-reported outcomes in guselkumab-treated patients with psoriatic arthritis.

Rahman Proton P McInnes Iain B IB Deodhar Atul A Schett Georg G Mease Phillip J PJ Shawi May M Cua Daniel J DJ Sherlock Jonathan P JP Kollmeier Alexa P AP Xu Xie L XL Sheng Shihong S Ritchlin Christopher T CT McGonagle Dennis D

Clinical rheumatology 20240312 5

<h4>Objectives</h4>To evaluate the association between enthesitis resolution (ER) and dactylitis resolution (DR) and meaningful improvements in patient-reported outcomes (PROs) among biologic-naïve patients with PsA receiving guselkumab in the DISCOVER-2 study.<h4>Methods</h4>Enthesitis and dactylitis, characteristic lesions of PsA, were evaluated by independent assessors using the Leeds Enthesitis Index (range, 0-6) and Dactylitis Severity Score (range, 0-60). Proportions of patients with ER or ...[more]

PMID: 38472528

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Project description:IntroductionSynovitis and enthesitis are key manifestations in psoriatic arthritis (PsA). This descriptive analysis investigated the association between improvement in synovitis and enthesitis, individually and combined, and improvement in patient-reported outcomes (PROs) including health-related quality of life (HRQoL) for patients with PsA from the SPIRIT-P1, SPIRIT-P2, and SPIRIT-H2H trials who presented with synovitis and enthesitis at baseline and received ixekizumab (IXE) treatment.MethodsIn this post hoc analysis, data are presented from patients with PsA treated with IXE every 4 weeks from two phase III studies (SPIRIT-P1 and SPIRIT-P2) and one phase IIIb/IV study (SPIRIT-H2H) who had both synovitis and enthesitis at baseline. Associations between improvements in synovitis and improvements in enthesitis were explored using Pearson analyses through week 52. Associations between improvements in both, either, and neither condition with improvements in PROs (36-item Short Form Health Survey Physical Component Score [SF-36 PCS], the European Quality-of-Life 5 Dimensions 5 Levels [EQ-5D-5L] including the EQ-5D Visual Analogue Score [VAS] and the EQ-health index, Patient's Global Assessment [PtGA], and pain VAS) were assessed descriptively through week 52.ResultsResults demonstrated the synergistic improvements in synovitis and enthesitis, individually or combined, and improvements in PROs including HRQoL, for patients treated with IXE through week 52. An association between improvements in synovitis and enthesitis symptoms was observed through week 52. Patients who achieved resolution of both synovitis and enthesitis reported highest improvements in SF-36 PCS, EQ-5D-5L, pain VAS, and PtGA.ConclusionSynergistic improvements in two key PsA domains, namely synovitis and enthesitis, and improvements in PROs including HRQoL, were observed for patients with PsA treated with IXE through week 52. These findings support PsA treatment goal aiming to achieve the lowest possible level of disease activity in all disease domains.Trial registration numbersSPIRIT-P1 (NCT01695239), SPIRIT-P2 (NCT02349295), and SPIRIT-H2H (NCT03151551).

Project description:BACKGROUND:Ixekizumab improves signs/symptoms of psoriatic arthritis (PsA). We present an integrated analysis of baseline disease burden and post-baseline outcomes in ixekizumab-treated patients with enthesitis or dactylitis. METHODS:Data from SPIRIT-P1 and SPIRIT-P2 were integrated. Patients with PsA were randomized to 80-mg ixekizumab every 4 weeks (IXEQ4W) or 2 weeks (IXEQ2W), after a 160-mg starting dose, or to placebo. Inadequate responders at week 16 received rescue therapy. Among patients with baseline enthesitis (Leeds Enthesitis Index [LEI] > 0) or dactylitis (Leeds Dactylitis Index-Basic [LDI-B] > 0), baseline characteristics and disease burden were reported. At week 24, LEI and LDI-B (percentage of patients with resolution [LEI = 0, LDI-B = 0]) were assessed. In pooled treatment groups, the impact of enthesitis or dactylitis resolution on health-related quality of life (HRQoL) (EuroQol-5 Dimensions Visual Analogue Scale [EQ-5D VAS]), physical function (Health Assessment Questionnaire-Disability Index [HAQ-DI]), and pain was assessed. RESULTS:The integrated analysis set comprised 679 patients; of these, 60% (n = 403 of 675) had baseline enthesitis (LEI > 0) and 23% (n = 155 of 676) had baseline dactylitis (LDI > 0). At week 24, ixekizumab-treated patients experienced significantly more resolution than placebo of enthesitis (39% IXEQ4W, 35% IXEQ2W, 21% placebo) and dactylitis (78% IXEQ4W, 65% IXEQ2W, 24% placebo). Furthermore, at entheseal points measured by the LEI, ixekizumab-treated patients had significantly higher resolution of enthesitis compared to placebo. At week 24, among all placebo- and ixekizumab-treated patients, resolution of enthesitis was associated with improvements in function and HRQoL whereas dactylitis resolution was associated with more limited improvements. The least squares mean HAQ-DI improvements from baseline were - 0.44 and - 0.25 for patients who did/did not resolve enthesitis, and - 0.41 and - 0.31 for patients who did/did not resolve dactylitis. EQ-5D VAS improvements were 12.3 and 5.8 for patients who did/did not resolve enthesitis, and 10.8 and 9.8 for patients who did/did not resolve dactylitis. CONCLUSIONS:Among patients with pre-existing enthesitis or dactylitis, IXEQ2W- and IXEQ4W-treatment resulted in significant improvements in enthesitis and dactylitis. Enthesitis resolution was associated with improvements in patients' function, pain, and HRQoL. TRIAL REGISTRATION:ClinicalTrials.gov, NCT01695239 , registered on September 25, 2012, and NCT02349295 , registered on October 10, 2014.

Project description:IntroductionEnthesitis is a core outcome domain assessed in psoriatic arthritis (PsA) clinical trials. Limited evidence describes the impact of enthesitis on patient-reported outcomes (PROs) and physician satisfaction with current treatment options. The objective of this analysis is to characterize the impact of enthesitis on PROs and physician satisfaction with currently available treatment in clinical practice settings.MethodsCross-sectional survey of rheumatologists, dermatologists, and their consulting patients with PsA in Australia, Canada, European Union (EU5), and the USA conducted in 2018. Physicians assessed current presence and severity of enthesitis, overall disease severity, other symptoms experienced, and their satisfaction with the current treatment. PsA participant self-reported data included current pain level, EQ5D, Psoriatic Arthritis Impact of Disease (PsAID12), Health Assessment Questionnaire Disability Index (HAQ-DI), and Work Productivity and Activity Impairment Index (WPAI-SHP). Bivariate descriptive analyses were conducted to describe features and outcomes in participants with and without enthesitis.ResultsRheumatologists (454) and dermatologists (238) provided information for 3157 participants with PsA. Mean participant age was 49.2 years, and 45.9% were female. Enthesitis was present currently in 6.5% (205) of participants with PsA. Those with enthesitis had worse overall disease severity compared to those without enthesitis (12.2% vs 2.2% severe) and had more extraarticular manifestations, including nail psoriasis, dactylitis, and sacroiliitis. Enthesitis was associated with more pain, worse quality of life (QoL), increased disability, and a negative impact on work. Participants with enthesitis had higher NSAIDs and opioid pain medication use but similar biologic use. Physicians were significantly less satisfied with current PsA treatment in participants with enthesitis versus without enthesitis.ConclusionsParticipants with psoriatic arthritis with enthesitis experienced significantly higher disease burden than those without enthesitis but were not more likely to receive advanced therapies. Physicians were significantly more dissatisfied with treatment in patients with enthesitis than in those without it.

Project description:ObjectiveThe Phase 3 DISCOVER-1 study of guselkumab is the first randomized controlled trial to use Patient-Reported Outcomes Measurement Information System (PROMIS) measures to assess the effects of treatment on general health outcomes in patients with psoriatic arthritis (PsA).MethodsPatients (N = 381) with active PsA were randomized 1:1:1 to guselkumab 100 mg every 4 weeks (Q4W); guselkumab 100 mg at Week 0, Week 4, then every 8 weeks (Q8W); or placebo with Week 24 crossover to guselkumab Q4W. The PROMIS-29 Profile contains four items for each of seven domains (anxiety, depression, fatigue, pain interference, physical function, sleep disturbance, and social participation) and one pain-intensity item. Raw domain scores are converted to standardized T-scores, with norms based on a US general population mean of 50 (1 standard deviation (SD) = 10). T-score changes of ≥ 5 are considered clinically meaningful. Least-squares mean PROMIS-29 T-score changes from baseline to Week 24 and Week 52 were summarized for the guselkumab and placebo groups; nominal p-values comparing results between guselkumab and placebo were calculated at Week 24 using a mixed model for repeated measures. The proportions of patients who achieved clinically meaningful improvement in PROMIS-29 T-scores were also summarized at Week 24 and Week 52; nominal p-values comparing results between guselkumab and placebo were calculated at Week 24 using the Cochran-Mantel-Haenszel test.ResultsIn the DISCOVER-1 patient population, mean PROMIS-29 T-scores at baseline were ~ 1 SD worse for physical function and pain interference and were numerically worse for social participation, fatigue, and sleep disturbance compared with the US general population. At Week 24, mean PROMIS-29 T-scores improved in guselkumab-treated patients, approaching US population norms; T-scores continued to improve through Week 52. Significantly higher proportions of patients in both guselkumab treatment arms (31-52% across domains) had clinically meaningful improvements in pain interference, fatigue, physical function, sleep, and social participation at Week 24 versus placebo (all nominal p ≤ 0.05).ConclusionIn patients with active PsA, guselkumab treatment provided clinically meaningful reductions in fatigue and pain and improvement in physical function and social participation, as measured by the PROMIS-29 Profile. These improvements were maintained through 1 year.ClinicaltrialsGOV: Registration number, NCT03162796; Submission date 19 May 2017.

Project description:BackgroundTo explore the effect of abatacept treatment on patient-reported outcomes (PROs) in psoriatic arthritis (PsA).MethodsPatients with PsA were randomised (1:1) to subcutaneous abatacept 125 mg weekly/placebo for 24 weeks with early escape (EE) to open-label abatacept (week 16). Adjusted mean changes from baseline to weeks 16 (all patients) and 24 (non-EE responders) in Health Assessment Questionnaire-Disability Index (HAQ-DI), Short Form-36 (SF-36; physical and mental component summary and domains), Dermatology Life Quality Index and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were evaluated. Subpopulations were analysed by baseline C-reactive protein (CRP) level (> vs ≤ upper limit of normal [ULN]) and prior tumour necrosis factor inhibitor (TNFi) exposure. Proportions of patients reporting improvements ≥ minimal clinically important differences (MCIDs) and ≥ normative values (NVs) in HAQ-DI, SF-36 and FACIT-F (week 16 before EE) were analysed.ResultsIn total population, numerically higher improvements in most PROs were reported with abatacept (n = 213) versus placebo (n = 211) at both time points (P > 0.05). Higher proportions of abatacept versus placebo patients reported PRO improvements ≥ MCID and ≥ NV at week 16. At week 16, all PRO improvements were numerically greater (P > 0.05) in patients with baseline CRP > ULN versus CRP ≤ ULN (all significant [95% confidence interval] for abatacept vs placebo); improvements in SF-36 component summaries and FACIT-F were greater in TNFi-naïve versus TNFi-exposed patients (abatacept > placebo). Week 24 subgroup data were difficult to interpret due to low patient numbers.ConclusionsAbatacept treatment improved PROs in patients with PsA versus placebo, with better results in elevated baseline CRP and TNFi-naïve subpopulations.Trial registrationClinicalTrials.gov number, NCT01860976 (funded by Bristol-Myers Squibb); date of registration: 23 May 2013.

Project description:BackgroundThis study examined the time to clinically meaningful response in patients with active psoriatic arthritis treated with tofacitinib, adalimumab, or placebo switching to tofacitinib.MethodsData 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.ResultsIn 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.ConclusionThis 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 registrationClinicalTrials.gov , NCT01877668. Registered June 12, 2013. ClinicalTrials.gov , NCT01882439. Registered June 18, 2013.

Dataset Information

Association between enthesitis/dactylitis resolution and patient-reported outcomes in guselkumab-treated patients with psoriatic arthritis.

Objectives

Methods

Results

Conclusion

Trial registration

Publications

Association between enthesitis/dactylitis resolution and patient-reported outcomes in guselkumab-treated patients with psoriatic arthritis.

Similar Datasets

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