Key Summary Points
Why carry out this study?Psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) are chronic immune-mediated inflammatory diseases that can result in functional disability and reduced quality of lifeDespite tumor necrosis factor inhibitor (TNFi) therapy substantially improving management of PsA and axSpA, many patients with these diseases are either not able to achieve or not able to maintain optimal disease controlTo better understand and improve treatment management of these chronic inflammatory diseases, this study assessed the achievement of low disease activity in a clinical practice setting in patients with PsA or axSpA who initiated and maintained a TNFi but did not achieve low disease activity after two consecutive follow-up visits over 12 months, compared with patients who successfully achieved low disease activityWhat was learned from the study?Despite initiating and maintaining TNFi therapy, approximately 70%–80% of patients with PsA and axSpA never achieved low disease activity at 6 months and almost 90% of these patients did not achieve low disease activity at 12 months.Patients with PsA or axSpA who do not respond to TNFi therapy at 6 months are unlikely to respond in the longer term if maintained on TNFi therapyThese findings highlight an unmet need for more effective treatment strategies to manage these complex, chronic inflammatory diseases as well as a need for healthcare providers to consider changes in therapy if treatment goals have not been met by 6 months
Introduction
Psoriatic arthritis (PsA) is a heterogeneous, chronic inflammatory disease that includes musculoskeletal (peripheral arthritis, enthesitis, dactylitis, and spondylitis) and dermatologic (skin and nail psoriasis) manifestations [1, 2]. Axial spondyloarthritis (axSpA) is also a chronic, inflammatory musculoskeletal disease that affects the axial skeleton (spine and sacroiliac joints) or peripheral joints and entheses [3, 4]. Both PsA and axSpA are progressive diseases that can result in structural damage, permanent disability, impaired work productivity, psychosocial impairment, and a substantial deterioration in quality of life (QoL) [5–13].
Phase 3 clinical trials have demonstrated that treatment of these immune-mediated inflammatory diseases with TNF inhibitors (TNFis), compared with placebo, not only reduces disease activity but also results in a decrease in joint pain, swelling, and tenderness; and slows the progression of joint damage [14–20]. As a result, TNFis are commonly used as first-line biologic therapy in the treatment of PsA and axSpA [21–25]. However, despite the effectiveness of TNFis in reducing inflammation and disease activity, and improving the symptoms and physical function in some patients suffering from PsA and axSpA, approximately 68% of patients with PsA [26] and approximately 67% of those with axSpA [27] are unable to reach optimal disease control.
At present, optimal disease control is considered to be the attainment of the treatment targets of remission or low disease activity [21–25]. This study aimed to quantify the proportion of patients with PsA and axSpA who never achieved low disease activity compared with those who achieved varying degrees of disease activity, including those who successfully achieved low disease activity among patients who initiated and maintained TNFi treatment for 12 months in a clinical practice setting.
Methods
Data Source
The PPD™ CorEvitas™ PsA/SpA Registry, which began enrolling patients in the USA in 2013, is a prospective multicenter, non-interventional registry for adult patients with PsA or SpA being treated by a rheumatologist. Demographics, disease duration, medical history (including current and prior treatments for PsA or SpA), smoking status, alcohol use, disease activity and severity, clinician- and patient-reported outcomes, comorbidities and adverse events, infections, hospitalizations, and other targeted safety outcomes are collected from patients and their rheumatologists during routine clinical visits using registry questionnaires. Blood collection and other diagnostic tests were not required for participation; however, relevant standard of care laboratory and imaging results were reported if available.
As of August 2023, the CorEvitas PsA/SpA Registry included patients from 68 private and academic clinical sites with 78 physicians throughout 30 states in the USA. The registry enrolled 6276 patients with PsA/SpA. The mean and median follow-up time for patients was 3.6 years and 2.9 years, respectively.
Patients were eligible to enroll in the Registry if they were ≥ 18 years old, able to provide written informed consent, and met one of the following criteria: (1) diagnosed with PsA and initiated (prescribed or started) an approved medication for the treatment of PsA at the time of enrollment; (2) met the Assessment of SpondyloArthritis international Society (ASAS) criteria for axSpA, including radiographic or non-radiographic criteria, and initiated (prescribed or started) an approved medication for the treatment of axSpA at the time of enrollment; (3) met the modified New York classification criteria for ankylosing spondylitis and initiated (prescribed or started) an approved medication for the treatment of ankylosing spondylitis at the time of enrollment. Patients were excluded from enrollment in the CorEvitas PsA/SpA Registry if they had a diagnosis of rheumatoid arthritis, systemic lupus erythematosus, or any other form of autoimmune inflammatory arthritis; or were participating in or planned to participate in a clinical trial of an interventional research study of a non-marketed or marketed investigational drug (e.g. phase 1–4 clinical drug trial, post-marketing study, or registry study where drug was being provided).
This study was performed in accordance with the Declaration of Helsinki and the Guidelines for Good Pharmacoepidemiology Practice. All participating investigators were required to obtain full board approval for conducting non-interventional research involving human patients with a limited dataset. Sponsor approval and continuing review were obtained through a central Institutional Review Board (IRB), namely, the New England Independent Review Board (NEIRB; no.
120160610). For academic investigative sites that did not receive authorization to use the central IRB, full board approval was obtained from their respective governing IRBs, and documentation of approval was submitted to the PPD™ clinical research business of Thermo Fisher Scientific (Waltham, MA, USA) before the site’s participation and initiation of any study procedures. All patients enrolled in the PPD™ CorEvitas™ PsA/SpA Registry were required to provide written informed consent and authorization before participating in the study.
PsA Study Population Criteria
The PsA observational cohort for this analysis included patients with PsA enrolled in the CorEvitas PsA/SpA Registry, who initiated (from April 2013–August 2022) and persisted on the same TNFi of any line of therapy at or after the enrollment visit. Patients could not switch to another TNFi to be included in this study. Patients had to have a clinical diagnosis of PsA made by the treating rheumatologist, not be in minimal disease activity (MDA)[28] at baseline, and have valid baseline, 6 (± 3)-month, and 12 (± 3)-month follow-up visits.
MDA was defined as meeting at least five of the seven MDA components: body surface area (BSA) ≤ 3%, Health Assessment Questionnaire Disability Index (HAQ-DI) ≤ 0.5, tender joint count (TJC) ≤ 1, swollen joint count (SJC) ≤ 1, patient pain on visual analog scale (VAS 0–100) ≤ 15, patient global assessment of arthritis (VAS 0–100) ≤ 20; and Spondyloarthritis Research Consortium of Canada Enthesitis Index ≤ 1.
For data analysis, patients with PsA were stratified into one of four subgroups (sustained, improved, worsened, or never achieved status, respectively) according to their MDA status at the 6- and 12-month follow-up visits (Table 1).Table 1Cohort definitions for psoriatic arthritis (MDA status) and axial spondyloarthritis (BASDAI50 status)MDA or BASDAI50 status groupMDA or BASDAI50 status at 6-month follow-up visitMDA or BASDAI50 status at 12-month follow-up visitSustainedYesYesImprovedNoYesWorsenedYesNoNever achievedNoNoBASDAI50 50% improvement from the original Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score, MDA minimal disease activity
Clinical and QoL Outcomes in Patients with PsA
Clinical features, stratified by MDA status, were assessed at the 6- and 12-month follow-up visits for each of the four subgroups (sustained, improved, worsened, or never achieved status, respectively) and included Clinical Disease Activity in Psoriatic Arthritis low disease activity (cDAPSA LDA) composite score [29, 30], enthesitis and dactylitis counts, and BSA ≤ 3%. The composite disease activity score, cDAPSA, was calculated as the sum of TJC, SJC, patient pain assessment, and patient global assessment of arthritis activity. Higher cDAPSA scores indicate more severe disease activity, and cDAPSA LDA was defined as a score ≤ 13.
Patient-reported outcomes (PROs) were also evaluated at the 6- and 12-month follow-up visits for the four subgroups of patients with PsA. These outcomes included the HAQ-DI, which is used to assess the impact of PsA on physical function [31] and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), which is a broad composite score consisting of six questions that assess the severity of fatigue, spinal and peripheral joint pain, localized tenderness, and morning stiffness [32, 33]. The BASDAI score has a range of 0 to 10 with scores ≥ 4 considered to indicate high disease activity [34].
PROs included individual VAS (0–100) scores for patient pain, patient fatigue, and severity of morning stiffness. Overall work impairment was derived from the work time missed and impairment while working domains of the Work Productivity and Activity Impairment (WPAI) questionnaire [35].
axSpA Study Population Criteria
The axSpA observational cohort for this analysis included patients with axSpA enrolled in the CorEvitas PsA/SpA Registry who initiated (from August 2013–August 2022) and persisted for 12 months on the same TNFi of any line of therapy, at or after the enrollment visit. Patients could not switch to another TNFi to be included in this study. Patients had to have a clinical diagnosis of axSpA as determined by the treating rheumatologist and have valid baseline and 6 (± 3)- and 12 (± 3)-month follow-up visits.
BASDAI was used to determine patient-reported disease activity in patients with axSpA. BASDAI50 was defined as a ≥ 50% improvement from the original BASDAI score at baseline.
For analysis of data, patients with axSpA were stratified into one of four subgroups (sustained, improved, worsened, or never achieved status, respectively) according to their BASDAI50 status at the 6- and 12-month follow-up visits (Table 1).
Clinical and QoL Outcomes in Patients with axSpA
Clinical features of axSpA, stratified by BASDAI50 status, were assessed at the 6- and 12-month follow-up visits for each of the four subgroups (sustained, improved, worsened, or never achieved status, respectively), and included the composite measures of Ankylosing Spondylitis Disease Activity Score (ASDAS), LDA, and ASAS40. The ASDAS consists of five questions about back pain, peripheral pain/swelling, duration of morning stiffness, patient global assessment of arthritis, and C-reactive protein; the ASDAS LDA is defined as an ASDAS score < 2.1 [32, 36]. The ASAS40 response is defined as a ≥ 40% improvement and an absolute improvement from baseline of ≥ 2 units (range 0–10) in ≥ 3 of the four components (patient’s global assessment of disease activity, spinal pain, physical function as measured by Bath Ankylosing Spondylitis Functional Index [BASFI], and stiffness) without any worsening in the remaining component [37].
PROs were also evaluated at the 6- and 12-month follow-up visits for the four subgroups of patients with axSpA stratified by BASDAI50 status. Outcomes included the ASAS Health Index (ASAS HI), BASDAI, and BASFI. ASAS HI contains 17 items that address a broad range of functioning, disability, and health relevant to axSpA [38], and scores range from 0 to 17, with lower scores indicating better overall health status.
BASFI consists of eight questions regarding function and two questions assessing a patient’s ability to cope with everyday life [39], and scores range from 0 to 10, with higher scores indicating greater functional disability. Additional PROs included individual VAS (0–100) scores for patient pain, patient fatigue, and morning stiffness severity. Overall work impairment was derived from the work time missed and impairment while working domains of the WPAI Impairment questionnaire [35].
Data Analysis in PsA and axSpA Cohorts
Baseline patient characteristics were summarized as the mean and standard deviation (SD) or as frequencies and percentages. The baseline visit was defined either as the visit coinciding with the reported TNFi initiation date or—if the initiation was between visits—as the visit immediately prior to the report of initiation if that visit occurred ≤ 4 months prior to the reported treatment initiation. If the visit at which initiation was reported > 1 month after initiation, the patient was excluded from the analysis for lack of treatment index data.
For patients in the sustained and never achieved subgroups, the frequency and proportion of patients achieving functional, clinical, and QoL outcomes were reported at the 6- and 12-month follow-up visits. Rates of achievement were calculated among patients who were not in the outcome state at baseline.
Poisson regression models, adjusting for age, race, sex, work status, time since PsA or axSpA diagnosis, and line of therapy (0, 1, 2+ prior biologic/targeted synthetic disease-modifying antirheumatic drug [DMARD] therapies) were used to estimate the association between disease status group (sustained vs never achieved status) and achievement of clinical outcomes as well as those who met or exceeded a minimum clinically important difference (MCID) in PROs at the 6- and 12-month follow-ups; covariate-adjusted relative risk ratios (95% confidence intervals [CIs]) were reported at both follow-up visits. MCIDs for PROs are summarized in Table 2.Table 2Minimum clinically important differences for patient-reported outcomes Patient-reported outcomesMinimum clinically important differenceHAQ-DI (0–3)≥ 0.35-point decreaseBASDAI VAS (0–10)≥ 1.1-point decreaseBASFI VAS (0–10)≥ 0.6-point decreaseASAS-HI VAS (0–17)≥ 3.0-point decreasePatient pain (VAS 0–100)≥ 10.0-point decreasePatient fatigue (VAS 0–100)≥ 10.0-point decreaseMorning stiffness severity (VAS 0–100)≥ 10.0-point decreaseOverall work impairment (0–100%)≥ 15.0-point decreaseASAS-HI Assessment of Spondyloarthritis international Society Health Index, BASDAI Bath Ankylosing Spondylitis Disease Activity Index, BASFI Bath Ankylosing Spondylitis Functional Index, HAQ-DI Health Assessment Questionnaire Disability Index, VAS visual analogue scale
Results
PsA—Baseline Characteristics by MDA Status
Of the 338 patients with PsA who initiated and persisted on TNFis, 35% (117/338) achieved MDA and 65% (221/338) did not achieve MDA at 6 months (Fig. 1). Of the patients who achieved MDA at 6 months, 76% (89/117) sustained MDA at 12 months and 24% (28/117) worsened.
Of those who did not achieve MDA at 6 months, 14% (32/221) improved and 86% (189/221) never achieved MDA at 12 months.Fig. 1PsA cohort selection and MDA achievement in patients with PsA who initiated and maintained TNFis through 12 months of follow-up. Numbers may not add up to 100% due to rounding.
MDA minimal disease activity, PsA psoriatic arthritis, TNFi tumor necrosis factor inhibitor
The proportion of female patients was higher in the never achieved subgroup compared with the sustained subgroup (66.0% vs 55.7%; Table 3). At baseline, PsA disease duration was greater in the never achieved MDA subgroup compared with the sustained MDA subgroup (6.3 vs 4.3 years). PsA disease activity measures and PRO symptomology varied across the MDA status groups.
At least 50% of patients in all MDA status subgroups were TNFi-treatment-naïve at baseline.Table 3Baseline characteristics in patients with psoriatic arthritis stratified by minimal disease activity statusBaseline characteristicsPsA subgroups according to MDA statusSustained, N = 89Improved, N = 32Worsened, N = 28Never achieved, N = 189Demographics Age (years), mean ± SD48.9 ± 14.952.9 ± 11.855.5 ± 10.157.3 ± 12.1 Female patients, n (%)49 (55.7)15 (46.9)17 (60.7)124 (66.0) Race, white, n (%)79 (91.9)29 (93.5)21 (77.8)170 (92.4)PsA disease characteristics, mean ± SD Years since PsA diagnosis4.3 ± 6.04.4 ± 5.86.0 ± 7.66.3 ± 7.4 Years since PsA symptom onset6.7 ± 8.46.9 ± 7.27.3 ± 6.710.5 ± 9.7PsA disease activity measures SJC, mean ± SD5.4 ± 6.03.8 ± 5.73.1 ± 2.94.6 ± 6.8 TJC, mean ± SD7.2 ± 7.84.0 ± 5.58.4 ± 9.59.2 ± 10.6 cDAPSA score, mean ± SD21.6 ± 14.317.1 ± 11.721.4 ± 11.825.9 ± 16.9 Presence of dactylitis, n (%)37 (41.6)4 (12.5)5 (17.9)28 (14.8) Presence of enthesitis, n (%)24 (27.0)4 (12.5)6 (21.4)70 (37.0) BASDAI VAS (0–10), mean ± SD4.6 ± 2.24.2 ± 2.15.0 ± 1.96.1 ± 1.9 BSA > 3%, n (%)28 (31.8)14 (45.2)8 (28.6)58 (31.9)PROs, mean ± SD Patient global assessment of arthritis VAS (0–100)38.5 ± 24.241.2 ± 23.649.9 ± 17.854.8 ± 21.9 Patient global assessment of arthritis and psoriasis VAS (0–100)39.7 ± 24.743.7 ± 22.947.2 ± 22.354.3 ± 21.2 HAQ-DI (0–3)0.7 ± 0.50.7 ± 0.61.0 ± 0.61.2 ± 0.6 Patient pain VAS (0–100)49.7 ± 26.547.7 ± 22.447.1 ± 25.064.3 ± 20.6 Patient fatigue VAS (0–100)43.7 ± 28.545.9 ± 28.648.2 ± 23.162.2 ± 23.0 Patient spine pain VAS (0–100)21.7 ± 24.730.7 ± 26.935.0 ± 27.649.6 ± 29.4 Morning stiffness VAS (0–100)51.8 ± 29.842.5 ± 24.649.3 ± 23.164.4 ± 23.9WPAI (0–100%), mean ± SD Work time missed5.7 ± 14.88.9 ± 24.125.8 ± 34.19.9 ± 23.5 Impairment while working24.8 ± 22.920.4 ± 18.536.6 ± 24.639.2 ± 24.5 Overall work impairment29.6 ± 25.221.9 ± 21.352.2 ± 31.744.7 ± 26.8 Activity impairment35.7 ± 28.135.1 ± 30.038.1 ± 25.453.5 ± 24.5Number of prior TNFis, n (%)a 058 (66.7)18 (58.1)17 (60.7)88 (50.3) 120 (23.0)11 (35.5)8 (28.6)58 (33.1) ≥ 29 (10.3)2 (6.5)3 (10.7)29 (16.6)BASDAI Bath Ankylosing Spondylitis Disease Activity Index, BSA body surface area, cDAPSA Clinical Disease Activity in Psoriatic Arthritis, HAQ-DI Health Assessment Questionnaire-Disability Index, MDA minimal disease activity, PROs patient-reported outcomes, PsA psoriatic arthritis, SD standard deviation, SJC swollen joint count, TJC tender joint count, TNFi tumor necrosis factor inhibitor, VAS visual analogue scale, WPAI Work Productivity and Activity Impairment QuestionnaireaDenominators included only those patients who had data for this variable
PsA—Achievement of Clinical and QoL Outcomes by MDA Status
Patients who never achieved MDA experienced higher disease activity compared with patients with sustained MDA at both 6 and 12 months (Fig. 2). Lower proportions of patients who never achieved MDA reported improvements in PROs that exceeded the MCID compared to patients with sustained MDA at both 6 and 12 months (Fig.
2). Based on the results from adjusted regression models, patients who never achieved MDA had a two- to threefold higher risk of not achieving disease activity measures and MCIDs in PROs compared with those who achieved sustained MDA over 12 months.Fig. 2a, b Proportion of patients in the sustained versus never achieved subgroups who achieved the PsA disease activity measures of cDAPSA LDA, enthesitis count = 0, dactylitis count = 0, TJC = 0, SJC = 0, and BSA ≤ 3% at 6 months (a) and 12 months (b). c, d Proportion of patients in the sustained versus never achieved subgroups who achieved MCIDs in the PROs HAQ-DI ≥ 0.35-point decrease, BASDAI ≥ 1.1-point decrease, patient pain ≥ 10.0-point decrease, patient fatigue ≥ 10.0-point decrease, morning stiffness severity ≥ 10.0-point decrease, and overall work impairment ≥ 15.0-point decrease at 6 months (c) and 12 months (d).
The adjusted models estimate the relative risk of sustained MDA vs never achieved MDA as the reference. BASDAI Bath Ankylosing Spondylitis Disease Activity Index, BSA body surface area, cDAPSA LDA Clinical Disease Activity Index for Psoriatic Arthritis Low Disease Activity, CI confidence interval, HAQ-DI Health Assessment Questionnaire Disability Index, MCID minimum clinically important difference, MDA minimal disease activity, PRO patient-reported outcome, PsA psoriatic arthritis, RR risk ratio, SJC swollen joint count, TJC tender joint count
axSpA—Baseline Characteristics by BASDAI50 Status
Of the 152 patients with axSpA who initiated and persisted on TNFis, 20% (31/152) achieved BASDAI50 and 80% (121/152) did not achieve BASDAI50 at 6 months (Fig. 3). Of those who achieved BASDAI50 at 6 months, 61% (19/31) sustained BASDAI50 at 12 months.
Of those who did not achieve BASDAI50 at 6 months, 91% (110/121) never achieved disease control at 12 months despite persistent TNFi treatment. At baseline, lower disease activity and PRO symptomology were reported among the subgroup that sustained BASDAI50 compared with the subgroup that never achieved BASDAI50 (Table 4). Across the BASDAI50 status groups, 55% of patients were TNFi treatment-naïve at baseline.Fig.
3axSpA cohort selection and BASDAI50 achievement in patients with axSpA who initiated and maintained TNFis through 12 months of follow-up. BASDAI50 was defined as 50% improvement in the BASDAI. axSpA axial spondyloarthritis, BASDAI Bath Ankylosing Spondylitis Disease Activity Index, TNFi tumor necrosis factor inhibitorTable 4Baseline characteristics in patients with axial spondyloarthritis stratified by 50% improvement from the original Bath Ankylosing Spondylitis Disease Activity Index statusBaseline characteristicsAxSpa subgroups according to BASDAI50 statusSustained, N = 19Improved, N = 11Worsened, N = 12Never achieved, N = 110Demographics Age (years), mean ± SD45.6 ± 15.148.5 ± 13.947.2 ± 14.253.0 ± 13.7 Female patients, n (%)7 (36.8)7 (63.6)4 (33.3)60 (55.0) Race, white, n (%)14 (73.7)10 (90.9)10 (83.3)100 (91.7)axSpA disease characteristics, mean ± SD Years since axSpA diagnosis7.4 ± 10.36.4 ± 7.37.6 ± 11.37.1 ± 10.1 Years since axSpA symptom onset13.0 ± 10.712.9 ± 9.212.0 ± 10.716.0 ± 12.0axSpA disease activity measures SJC, mean ± SD0.5 ± 1.30.7 ± 1.60.5 ± 1.21.5 ± 3.0 TJC, mean ± SD1.1 ± 2.22.7 ± 4.02.0 ± 5.24.4 ± 11.4 Presence of dactylitis, n (%)1 (5.3)1 (9.1)0 (0.0)6 (5.5) Presence of enthesitis, n (%)6 (31.6)2 (18.2)3 (25.0)35 (31.8) ASDAS, mean ± SD2.9 ± 0.92.5 ± 1.02.7 ± 0.72.8 ± 1.2 HLA-B27 positive, n (%)9 (47.4)4 (36.4)7 (58.3)40 (36.4) Elevated CRP, n (%)6 (31.6)4 (36.4)0 (0.0)25 (22.7)PROs, mean ± SD Patient global assessment of arthritis VAS (0–100)48.5 ± 2.175.2 ± 30.661.0 ± 19.155.8 ± 24.5 ASAS-HI VAS (0–17)4.1 ± 2.97.4 ± 3.55.5 ± 2.18.2 ± 4.0 BASFI VAS (0–10)2.6 ± 2.32.8 ± 1.53.6 ± 1.64.1 ± 2.8 HAQ-DI (0–3)0.8 ± 0.60.6 ± 0.30.6 ± 0.30.9 ± 0.7 Patient pain VAS (0–100)49.6 ± 32.246.0 ± 25.464.3 ± 19.353.0 ± 27.0 Patient fatigue VAS (0–100)44.4 ± 33.742.8 ± 31.558.2 ± 22.952.0 ± 30.4 Patient spine pain at night VAS (0–100)41.1 ± 32.446.4 ± 28.056.3 ± 31.946.3 ± 30.6 Morning stiffness VAS (0–100)60.4 ± 32.147.5 ± 28.364.3 ± 27.551.7 ± 30.1WPAI questionnaire (0–100%), mean ± SD Work time missed5.2 ± 13.86.4 ± 11.16.5 ± 16.69.2 ± 23.0 Impairment while working31.6 ± 26.233.8 ± 29.534.2 ± 26.334.8 ± 31.8 Overall work impairment35.3 ± 28.237.2 ± 32.736.9 ± 22.237.8 ± 32.6 Activity impairment34.4 ± 29.629.0 ± 15.547.6 ± 20.648.0 ± 30.7Number of prior TNFis, n (%)a 010 (58.8)6 (54.5)8 (72.7)54 (52.4) 14 (23.5)5 (45.5)2 (18.2)37 (35.9) ≥ 23 (17.6)0 (0.0)1 (9.1)12 (11.7)ASAS-HI Assessment of Spondyloarthritis international Society Health Index, ASDAS Ankylosing Spondylitis Disease Activity score, axSpA axial spondyloarthritis, BASDI Bath Ankylosing Spondylitis Disease Activity Index, BASDAI50 50% improvement from the original BASDAI score at baseline, BASFI Bath Ankylosing Spondylitis Functional Index, CRP C-reactive protein, HAQ-DI Health Assessment Questionnaire-Disability Index, HLA-B27 human leukocyte antigen B27, PROs patient-reported outcomes, PsA psoriatic arthritis, SD standard deviation, SJC swollen joint count, TJC tender joint count, TNFi tumor necrosis factor inhibitor, VAS visual analogue scale, WPAI Work Productivity and Activity ImpairmentaDenominators included only those patients who had data for this variable
axSpA—Achievement of Clinical and QoL Outcomes by BASDAI50 Status
Patients who never achieved BASDAI50 experienced higher disease activity and worse PROs at 6 and 12 months versus those with sustained BASDAI50 (e.g., ASDAS LDA at 6 months was 14% vs 88%, and at 12 months was 9% vs 100%, respectively; Fig. 4). The adjusted regression models demonstrated that patients who never achieved BASDAI50 had at least a twofold higher risk of not achieving disease activity measures and MCIDs in PROs compared with those who achieved sustained BASDAI50.
Similar improvements were observed in ASAS40 and ASAS HI for those patients with sustained BASDAI50 at 6 and 12 months (Electronic Supplementary Material Fig. S1); however, these data should be interpreted with caution due to the limited sample size.Fig. 4a, b Proportion of patients in the sustained versus never achieved subgroups who achieved the axSpA disease activity measures of ASDAS LDA, BASFI ≥ 0.6-point decrease, and BASDAI ≥ 1.1-point decrease at 6 months (a) and 12 months (b). c, d Proportion of patients in the sustained versus never achieved subgroups who achieved MCIDs in the PROs of patient pain ≥ 10.0-point decrease, patient fatigue ≥ 10.0-point decrease, morning stiffness severity ≥ 10.0-point decrease, and overall work impairment ≥ 15.0-point decrease at 6 months (c) and 12 months (d).
The adjusted models estimate the relative risk of sustained BASDAI50 vs never achieved BASDAI50 as the reference. ASDAS Ankylosing Spondylitis Disease Activity Score, axSpA axial spondyloarthritis, BASDAI Bath Ankylosing Spondylitis Disease Activity Index, BASFI Bath Ankylosing Spondylitis Functional Index, CI confidence interval, LDA low disease activity, MCID minimum clinically important difference, PRO patient-reported outcome, RR risk ratio
Discussion
Psoriatic arthritis and axSpA are both chronic inflammatory diseases that significantly impact QoL and functional abilities [5, 10–12, 22, 40, 41]. Despite the success of TNFis in the management of these diseases, many patients with PsA and axSpA experience suboptimal disease control [26, 27]. Patients unable to achieve good disease control within 6 months are at increased risk of further joint damage and also may be at increased risk for extra-musculoskeletal manifestations such as psoriasis, uveitis, and inflammatory bowel disease, as well as cardiovascular disease, metabolic syndrome, liver disease, depression, and anxiety [42–48].
Patients with higher levels of disease activity also have greater healthcare resource utilization and higher medical costs [49]. All of this highlights the need for healthcare providers to reconsider the management of patients who do not achieve treatment goals.
In the PsABio real-world, international observational cohort study, approximately 32% of TNFi-treated patients with PsA achieved the treatment goal of MDA at 6 months [26]. These results are comparable to those observed in our study in the USA in which approximately 35% of patients with PsA who were treated with TNFi achieved MDA at 6 months. For axSpA, data from the EuroSpA research collaboration showed that 27% of patients treated with TNFi in clinical practice achieved ASDAS inactive disease at 6 months [27].
In our study, where disease activity was assessed by BASDAI, 20% of patients achieved BASDAI50 at 6 months. Thus, less than half of the patients with axSpA in the European studies and in this study in the USA who were treated with TNFi achieved their treatment target of low disease activity at 6 months.
In our study in patients with PsA, we found that approximately seven out of ten patients who initiated a TNFi and persisted on therapy never achieved MDA at 6 months, with almost 90% of these patients still not achieving MDA at 12 months. In patients with axSpA, approximately eight out of ten patients who initiated a TNFi and persisted on therapy never achieved BASDAI50 at 6 months and 90% never achieved BASDAI50 at 12 months. Patients with PsA or axSpA who did not respond to treatment at 6 months were not likely to respond in the longer term if maintained on TNFi therapy.
For both PsA and axSpA, patients who never achieved MDA and BASDAI50, respectively, reported higher disease activity at 6 and 12 months, characterized by worse clinical outcomes and PROs, highlighting the importance of achieving low disease activity early and identifying and managing risk factors for non-response to therapy such as obesity.
Our findings indicate that patients with PsA or axSpA should be closely monitored for failure to achieve clinically meaningful improvements in disease activity at approximately 6 months following initiation of their treatment regimen. Assessment of these patients should include all domains of the disease (i.e., axial disease, peripheral arthritis, enthesitis, dactylitis, psoriatic nail disease, skin psoriasis, inflammatory bowel disease, and uveitis) [22, 23]. Consideration should also be given to the level of pain experienced by the patient, the impact of the disease on QoL, physical function, and structural damage, as well as comorbidities and related conditions and the patient’s own treatment goals [22, 23, 50].
Comorbidities, such as fibromyalgia and depression/anxiety, can greatly impact clinical disease activity indices in patients with PsA [51, 52]. Patients who have both PsA and fibromyalgia have been reported to have worse QoL and greater functional impairment compared with those with PsA only [52]. Patients who have both PsA and fibromyalgia are less likely to achieve MDA (risk ratio = 0.57, 95% CI 0.45–0.71; p < 0.0001) [51].
While the Registry captures fibromyalgia and other comorbid conditions, this study’s sample size limited our ability to adjust for all factors, potentially leading to a small degree of residual confounding.
It is important to keep in mind additional limitations of this study when interpreting the results. Given this is a non-interventional registry, patients are not randomly assigned to an intervention and patient follow-up in a registry is not encouraged as it is in clinical trials. However, compared to clinical trials, the patient population included in a registry is broader, with a larger range of comorbidities, demographic characteristics, disease severity, and is more generalizable to the population of patients with PsA and axSpA.
There are potential biases, such as selection bias in registry data based on how patients are enrolled, and how data are collected over time. Physicians and patients volunteer to participate in the Registry; therefore, the population may not be representative of the general population of patients with PsA and axSpA. Patients were required to have three consecutive visits from the initiation of a TNFi through 12 months of follow-up.
Fulfilling this requirement may have excluded patients who missed one or two visits—patients who are doing well may tend to skip interim visits—so this study may have underestimated the effects and limited the generalizability of the results to the population of patients with PsA and axSpA who persist on therapy for 12 months. Missing or incomplete data may also represent a potential bias; however, the CorEvitas PsA/SpA Registry has minimal missing data values (< 5%) in disease demographic, lifestyle and disease activity, and PRO variables among patients with follow-up visits. Although the objective of this study was to quantify the proportion of patients with PsA and axSpA by varying degrees of disease activity achievement compared with those who sustained low disease activity control among patients who initiated and sustained TNFi treatment for 12 months in a clinical practice setting, the improved and worsened groups were not discussed in more detail because the sample size in these subgroups does not allow for strong conclusions or interpretation of results; therefore, we kept our focus on the sustained and never achieved groups for interpretation and conclusions.
Furthermore, the small sample size of the axSpA group impacted the power of this study to detect statistically significant differences, likely impacted the interpretation of the outcomes, and limited the generalizability of the findings.
Conclusions
In summary, a majority of patients with PsA and axSpA did not achieve treatment targets despite sustained TNFi therapy, underscoring an unmet need for more effective treatment strategies or personalized medicine approaches to manage these complex, chronic inflammatory diseases. Patients with PsA or axSpA who did not respond to treatment at 6 months were not likely to respond in the longer term if maintained on TNFi therapy. Both PsA and axSpA patients who never achieved treatment goals reported a greater disease activity at 6 and 12 months, characterized by worse clinical and patient-reported outcomes, highlighting the importance of achieving low disease activity and the need for healthcare providers to consider changes in therapy before 12 months if treatment goals have not been met by 6 months.
Supplementary Information
Below is the link to the electronic supplementary material.Supplementary file1 (PDF 156 KB)