Achievement of higher thresholds of clinical responses and lower levels of disease activity is associated with improvements in workplace and household productivity in patients with axial spondyloarthritis

Background: Patients with active axial spondyloarthritis (axSpA) exhibit more absences and lower levels of productivity in the workplace and household than the general population, which can improve upon treatment. Objectives: The objective of this study is to determine the long-term impact of achieving different levels of clinical response or disease activity on workplace and household productivity in patients with axSpA. Design: RAPID-axSpA (NCT01087762) was a 204-week phase III trial evaluating the safety and efficacy of certolizumab pegol (CZP) in adult patients with active axSpA. Methods: The impact of axSpA on workplace and household productivity was evaluated using the validated arthritis-specific Work Productivity Survey. Outcomes included the percentage of patients achieving Assessment of SpondyloArthritis International Society (ASAS) response and Ankylosing Spondylitis Disease Activity Score (ASDAS) thresholds. This post hoc study used a generalised estimating equations model to determine the association between the threshold of clinical response achieved and patient productivity. Results: Of 218 CZP-randomised patients, 65.1% completed week 204. At baseline, 72.0% were employed outside the home. Of the patients who were unemployed, 42.6% were unable to work due to arthritis. Achievement of higher treatment response thresholds, such as clinical remission, was associated with fewer days affected by workplace absenteeism (ASAS-partial remission: 4.0 days, ASAS40: 8.6 days, ASAS20 but not reaching ASAS40 response: 29.4 days, ASAS20 non-response: 69.2 days; ASDAS-inactive disease: 5.0 days, ASDAS-low disease activity: 15.6 days, ASDAS-high disease activity: 32.7 days, ASDAS-very high disease activity: 93.4 days). Similar associations were found for workplace presenteeism, and household absenteeism and presenteeism. Conclusions: Over 4 years, achievement of higher clinical response thresholds and lower levels of disease activity was associated with fewer cumulative days affected by absenteeism or presenteeism, with clinical remission associated with the greatest improvements in productivity. This highlights the importance of targeting these thresholds to limit the burden of axSpA on society and on patients’ daily lives

Comparative efficacy and safety of bimekizumab in axial spondyloarthritis: a systematic literature review and network meta-analysis

OBJECTIVES: To compare the efficacy and safety of bimekizumab 160 mg every 4 weeks, a selective inhibitor of interleukin‑17F and 17A, with biologic/targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) in non-radiographic axial spondyloarthritis (nr-axSpA) and ankylosing spondylitis (AS). METHODS: A systematic literature review identified randomised controlled trials until January 2023 for inclusion in Bayesian network meta-analyses (NMAs), including three b/tsDMARDs exposure networks: predominantly-naïve, naïve, and experienced. Outcomes were Assessment of SpondyloArthritis international Society (ASAS)20, ASAS40, and ASAS partial remission (PR) response rates at 12-16 weeks. A safety NMA investigated discontinuations due to any reason and serious adverse events at 12-16 weeks. RESULTS: The NMA included 36 trials. The predominantly-naïve network provided the most comprehensive results. In the predominantly-naïve nr-axSpA analysis, bimekizumab had significantly higher ASAS20 response rates vs secukinumab 150 mg (with loading dose [LD]/without LD), and comparable response rates vs other active comparators. In the predominantly-naïve AS analysis, bimekizumab had significantly higher ASAS40 response rates vs secukinumab 150 mg (without LD), significantly higher ASAS-PR response rates vs secukinumab 150 mg (with LD), and comparable response rates vs other active comparators. Bimekizumab demonstrated similar safety to other b/tsDMARDs. CONCLUSION: Across ASAS outcomes, bimekizumab was comparable to most b/tsDMARDs, including ixekizumab, TNF inhibitors and upadacitinib, and achieved higher response rates vs secukinumab for some ASAS outcomes in predominantly b/tsDMARD-naïve nr-axSpA and AS patients at 12-16 weeks. In a pooled axSpA network, bimekizumab demonstrated comparable safety vs other b/tsDMARDs

Nonsteroidal Antiinflammatory Drug Use and Association With Incident Hypertension in Ankylosing Spondylitis.

ObjectiveNonsteroidal antiinflammatory drugs (NSAIDs) increase blood pressure and potentially cardiovascular burden, which may limit their use in ankylosing spondylitis (AS). Our objective was to determine the association of NSAID use with incident hypertension in a longitudinal AS cohort.MethodsAdults with AS were enrolled in a prospective cohort study of patient outcomes and examined every 4-6 months. Hypertension was defined by patient-reported hypertension; antihypertensive medication use; or, on 2 consecutive visits, systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg. Continuous NSAID use was dichotomized based on the validated NSAID index. We assessed the association of NSAID use as a time-varying exposure with the incidence of hypertension using Cox proportional hazards models.ResultsOf the 1,282 patients in the cohort, 628 patients without baseline hypertension had at least 1 year of follow-up and were included in the analysis. Of these, 72% were male, the mean age at baseline was 39 ± 13 years, and 200 patients used NSAIDs continuously. On follow-up, 129 developed incident hypertension. After controlling for other variables, continuous NSAID use was associated with a hazard ratio of 1.12 for incident hypertension (95% confidence interval 1.04-1.20), compared to noncontinuous or no use. The association did not differ in subgroups defined by age, body mass index, biologic use, or disease activity.ConclusionIn our prospective, longitudinal AS cohort, continuous NSAID use was associated with a 12% increased risk for the development of incident hypertension, as compared to noncontinuous or no NSAID use

Examining Treatment Decision-Making Among Patients With Axial Spondyloarthritis: Insights From a Conjoint Analysis Survey

OBJECTIVE: The number of therapies for axial spondyloarthritis (axSpA) is increasing. Thus, it has become more challenging for patients and physicians to navigate the risk-benefit profiles of the various treatment options. In this study, we used conjoint analysis-a form of trade-off analysis that elucidates how people make complex decisions by balancing competing factors-to examine patient decision-making surrounding medication options for axSpA. METHODS: We conducted an adaptive choice-based conjoint analysis survey for patients with axSpA to assess the relative importance of medication attributes (eg, chance of symptom improvement, risk of side effects, route of administration, etc) in their decision-making. We also performed logistic regression to explore whether patient demographics and disease characteristics predicted decision-making. RESULTS: Overall, 397 patients with axSpA completed the conjoint analysis survey. Patients prioritized medication efficacy (importance score 26.8%), cost (26.3%), and route of administration (13.9%) as most important in their decision-making. These were followed by risk of lymphoma (9.5%), dosing frequency (7.2%), risk of serious infection (6.0%), tolerability of side effects (5.3%), and clinic visit and laboratory test frequency (4.8%). In regression analyses, there were few significant associations between patients\u27 treatment preferences and sociodemographic and axSpA characteristics. CONCLUSIONS: Treatment decision-making in axSpA is highly individualized, and demographics and baseline disease characteristics are poor predictors of individual preferences. This calls for the development of online shared decision-making tools for patients and providers, with the goal of selecting a treatment that is consistent with patients\u27 preferences

A Fifty-Two-Week, Randomized, Placebo-Controlled Trial of Certolizumab Pegol in Nonradiographic Axial Spondyloarthritis

OBJECTIVE: The natural history of nonradiographic axial spondyloarthritis (SpA) is incompletely characterized, and there are concerns that nonsteroidal antiinflammatory drugs provide inadequate disease control in patients with active disease. This study was undertaken to investigate the effects of certolizumab pegol (CZP), an anti-tumor necrosis factor treatment, in patients with nonradiographic axial SpA with objective signs of inflammation. METHODS: In this ongoing parallel-group double-blind study, adults with active disease were recruited from 80 centers in Australia, Europe, North America, and Taiwan, and were randomized 1:1 to receive placebo or CZP (400 mg at weeks 0, 2, and 4, followed by 200 mg every 2 weeks) in addition to nonbiologic background medication (NBBM). Switching to open-label CZP (or other biologic) or making background medication changes was permitted at any point during the trial, although changes before week 12 were discouraged. The primary end point was the proportion of patients achieving major improvement (MI) (i.e., a \u3e /=2.0-point decrease in the score from baseline or achievement of the lowest possible score [0.6]) in the Ankylosing Spondylitis Disease Activity Score (ASDAS) at week 52. RESULTS: A total of 317 patients were randomized to receive placebo plus NBBM (n = 158) or CZP plus NBBM (n = 159). ASDAS-MI at week 52 was achieved in 47.2% (75 of 159) of CZP plus NBBM patients, which was significantly greater (P \u3c 0.0001) than the 7.0% (11 of 158) of placebo plus NBBM patients in whom ASDAS-MI was achieved. Of the placebo plus NBBM patients, 60.8% (96 of 158) switched to open-label treatment before week 52 compared to 12.6% (20 of 159) of the CZP plus NBBM patients. CONCLUSION: Adding CZP to background medication is superior to adding placebo in patients with active nonradiographic axial SpA. These results indicate that remission in nonradiographic axial SpA treated without biologics occurs infrequently, demonstrating the need for treatment beyond nonbiologic therapy. Inc. on behalf of American College of Rheumatology

Ustekinumab Safety in Psoriasis, Psoriatic Arthritis, and Crohn’s Disease:an integrated analysis of Phase II/III Clinical Development Programs

IntroductionTheoretical risks of biologic agents remain under study.ObjectiveThe aim of this study was to integrate 1-year safety data from 12 ustekinumab registrational trials.MethodsPatients had moderate-to-severe plaque psoriasis, active psoriatic arthritis (PsA) (± methotrexate), or moderate-to-severe Crohn's disease (CD; failed/intolerant of immunomodulators/corticosteroids). Psoriatic patients received subcutaneous ustekinumab 45/90 mg or placebo, generally at week 0, week 4, then every 12 weeks thereafter, while those with CD received a single intravenous ustekinumab dose (130 mg or weight range-based dosing of approximately 6 mg/kg) or placebo induction dose at week 0, followed by subcutaneous ustekinumab 90 mg at week 8 and every 8/12 weeks thereafter. The incidence rates of a priori-defined safety events were integrated post hoc (adjusted for duration of follow-up, reported per 100 patient-years [PYs]).ResultsAmong 6280 enrolled patients, 5884 ustekinumab-treated patients (psoriasis: 3117; PsA: 1018; CD: 1749) contributed 4521 PYs versus 674 PYs in placebo-treated patients through year 1 (829 PYs and 385 PYs during 8- to 16-week controlled periods). Combined across diseases among ustekinumab- versus placebo-treated patients, respective incidences/100 PYs (95% confidence intervals) of infections were 125.4 (122.2-128.7) versus 129.4 (120.9-138.3) through year 1, and not meaningfully increased in patients who did versus those who did not receive methotrexate (92.5 [84.2-101.5] vs. 115.3 [109.9-121.0]), or significantly increased in patients who did versus those who did not receive corticosteroids (116.3 [107.3-125.9] vs. 107.3 [102.0-112.8]) at baseline. Major adverse cardiovascular events (0.5 [0.3-0.7] vs. 0.3 [0.0-1.1]), malignancies (0.4 [0.2-0.6] vs. 0.2 [0.0-0.8]), and deaths (0.1 [0.0-0.3] vs. 0.0 [0.0-0.4]) were rare across indications.ConclusionsUstekinumab demonstrated a favorable and consistent safety profile across registrational trials in approved indications.Trial registrationsClinicalTrials.gov identifier: NCT00320216, NCT00267969, NCT00307437, NCT00454584, NCT00267956, NCT01009086, NCT01077362, NCT00265122, NCT00771667, NCT01369329, NCT01369342, and NCT01369355

Axial Involvement in Psoriatic Arthritis cohort (AXIS): the protocol of a joint project of the Assessment of SpondyloArthritis international Society (ASAS) and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).

BACKGROUND: Involvement of the axial skeleton (sacroiliac joints and spine) is a relatively frequent manifestation associated with psoriatic skin disease, mostly along with involvement of peripheral musculoskeletal structures (peripheral arthritis, enthesitis, dactylitis), which are referred to as psoriatic arthritis (PsA). Data suggest that up to 30% of patients with psoriasis have PsA. Depending on the definition used, the prevalence of axial involvement varies from 25% to 70% of patients with PsA. However, there are currently no widely accepted criteria for axial involvement in PsA.Objective: The overarching aim of the Axial Involvement in Psoriatic Arthritis (AXIS) study is to systematically evaluate clinical and imaging manifestations indicative of axial involvement in patients with PsA and to develop classification criteria and a unified nomenclature for axial involvement in PsA that would allow defining a homogeneous subgroup of patients for research. DESIGN: Prospective, multicenter, multinational, cross-sectional study. METHODS AND ANALYSES: In this multicenter, multinational, cross-sectional study, eligible patients [adult patients diagnosed with PsA and fulfilling Classification Criteria for Psoriatic Arthritis (CASPAR) with musculoskeletal symptom duration of ⩽10 years not treated with biological or targeted synthetic disease-modifying anti-rheumatic drugs] will be recruited prospectively. They will undergo study-related clinical and imaging examinations. Imaging will include radiography and magnetic resonance imaging examinations of sacroiliac joints and spine. Local investigators will evaluate for the presence of axial involvement based on clinical and imaging information which will represent the primary outcome of the study. In addition, imaging will undergo evaluation by central review. Finally, the central clinical committee will determine the presence of axial involvement based on all available information. ETHICS: The study will be performed according to the ethical principles of the Declaration of Helsinki and International Council for Harmonisation Good Clinical Practice guidelines. The study protocol will be approved by the individual Independent Ethics Committee / Institutional Review Board of participating centers. Written informed consent will be obtained from all included patients.Registration: ClinicalTrials.gov ID: NCT04434885

Axial Involvement in Psoriatic Arthritis cohort (AXIS): the protocol of a joint project of the Assessment of SpondyloArthritis international Society (ASAS) and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).

BACKGROUND: Involvement of the axial skeleton (sacroiliac joints and spine) is a relatively frequent manifestation associated with psoriatic skin disease, mostly along with involvement of peripheral musculoskeletal structures (peripheral arthritis, enthesitis, dactylitis), which are referred to as psoriatic arthritis (PsA). Data suggest that up to 30% of patients with psoriasis have PsA. Depending on the definition used, the prevalence of axial involvement varies from 25% to 70% of patients with PsA. However, there are currently no widely accepted criteria for axial involvement in PsA.Objective: The overarching aim of the Axial Involvement in Psoriatic Arthritis (AXIS) study is to systematically evaluate clinical and imaging manifestations indicative of axial involvement in patients with PsA and to develop classification criteria and a unified nomenclature for axial involvement in PsA that would allow defining a homogeneous subgroup of patients for research. DESIGN: Prospective, multicenter, multinational, cross-sectional study. METHODS AND ANALYSES: In this multicenter, multinational, cross-sectional study, eligible patients [adult patients diagnosed with PsA and fulfilling Classification Criteria for Psoriatic Arthritis (CASPAR) with musculoskeletal symptom duration of ⩽10 years not treated with biological or targeted synthetic disease-modifying anti-rheumatic drugs] will be recruited prospectively. They will undergo study-related clinical and imaging examinations. Imaging will include radiography and magnetic resonance imaging examinations of sacroiliac joints and spine. Local investigators will evaluate for the presence of axial involvement based on clinical and imaging information which will represent the primary outcome of the study. In addition, imaging will undergo evaluation by central review. Finally, the central clinical committee will determine the presence of axial involvement based on all available information. ETHICS: The study will be performed according to the ethical principles of the Declaration of Helsinki and International Council for Harmonisation Good Clinical Practice guidelines. The study protocol will be approved by the individual Independent Ethics Committee / Institutional Review Board of participating centers. Written informed consent will be obtained from all included patients.Registration: ClinicalTrials.gov ID: NCT04434885