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1.
J Rheumatol ; 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33722941

RESUMO

At the 2020 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), the International Dermatology Outcome Measures (IDEOM) Initiative Psoriasis (PsO) Working Group presented an update on its work to agree on meaningful, valid, and feasible outcome measures for PsO randomized controlled trials and longitudinal observational studies. The Treatment Satisfaction Working Group presented the development of a treatment satisfaction instrument to be utilized in PsO clinical trials. The Musculoskeletal Symptoms Working Group presented an overview of their work conducted to date to define how to best measure musculoskeletal symptoms in PsO clinical studies, and discussed next steps during an open-panel discussion, which included PsO and psoriatic arthritis experts.

3.
J Rheumatol ; 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33649070

RESUMO

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Outcome Measures in Rheumatology (OMERACT) Psoriatic Arthritis (PsA) Working Group provided updates at the 2020 GRAPPA annual meeting on its work toward developing a core outcome set for PsA. Working groups were set up for the 4 prioritized domains: enthesitis, fatigue, structural damage, and physical function. Two instruments for measurement of physical function were provisionally endorsed: (1) the Health Assessment Questionnaire-Disability Index and (2) the physical functioning domain in the Medical Outcomes Study 36-item Short Form survey.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33590829

RESUMO

OBJECTIVE: To evaluate the impact of upadacitinib vs placebo and adalimumab treatment, on patient-reported outcomes (PROs) in SELECT-COMPARE in an active RA population with inadequate responses to methotrexate (MTX-IR). METHODS: PROs in patients receiving upadacitinib (15 mg QD), placebo, or adalimumab (40 mg EOW) while on background MTX were evaluated over 48 weeks. PROs included PtGA and pain by VAS, HAQ-DI, 36-Item Short Form Survey (SF-36), morning (AM) stiffness duration and severity, FACIT-F, and work instability. Least squares mean (LSM) changes and proportions of patients reporting improvements ≥ minimal clinically important differences (MCID) and scores ≥ normative values were evaluated. RESULTS: Upadacitinib and adalimumab resulted in greater LSM changes from baseline vs placebo across all PROs (p < 0.05) at week 12, and pain and AM stiffness severity (p < 0.05) at week 2. More upadacitinib- vs placebo-treated (p < 0.05) and similar percentages of upadacitinib- vs adalimumab-treated patients reported improvements ≥ MCID across all PROs at week 12. Upadacitinib vs adalimumab resulted in greater LSM changes from baseline in PtGA, pain, HAQ-DI, stiffness severity, FACIT-F, and SF-36 Physical Component Summary (PCS) (all p < 0.05) at week 12. More upadacitinib- vs adalimumab-treated patients reported scores ≥ normative values in HAQ-DI and SF-36 PCS (p < 0.05) at week 12. More upadacitinib- vs adalimumab-treated patients maintained clinically meaningful improvements in PtGA, pain, HAQ-DI, FACIT-F, and AM stiffness through 48 weeks. CONCLUSION: In MTX-IR patients with RA, treatment with upadacitinib resulted in statistically significant and clinically meaningful improvements in PROs equivalent to or greater than with adalimumab.

6.
Semin Arthritis Rheum ; 51(2): 367-386, 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33601193

RESUMO

BACKGROUND: Structural damage is as an important outcome in the Psoriatic Arthritis (PsA) Core Domain Set and its assessment is recommended at least once in the development of a new drug. OBJECTIVES: To conduct a systematic review (SR) to identify studies addressing the measurement properties of radiographic outcome instruments for structural damage in PsA and appraise the evidence through the Outcome Measures in Rheumatology (OMERACT) Filter 2.1 Framework Instrument Selection Algorithm (OFISA). METHODS: A SR was conducted using search strategies in EMBASE and MEDLINE to identify full-text English studies which aimed to develop or assess the measurement properties of radiographic outcome instruments in PsA. Determination of eligibility and data extraction was performed independently by two reviewers with input from a third to achieve consensus. Two reviewers assessed the methodology and results of eligible studies and synthesized the evidence using OMERACT methodology. RESULTS: Twelve articles evaluating radiographic instruments were included. The articles assessed nine peripheral (hands, wrists and/or feet) and six axial (spinal and/or sacroiliac joints) radiographic instruments. The peripheral radiographic instruments with some evidence for reliability, cross-sectional construct validity and longitudinal construct validity were the Ratingen and modified Sharp van der Heijde scores. No instruments had evidence for clinical trial discrimination or thresholds of meaning. There was limited evidence for the measurement properties of all identified axial instruments. CONCLUSION: There are significant knowledge gaps in the responsiveness of peripheral radiographic instruments. Axial radiographic instruments require further validation, and the need to generate novel instruments and utilise other imaging modalities should be considered.

7.
Lupus ; 30(4): 578-586, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33413006

RESUMO

OBJECTIVES: Fatigue is one of the most common symptoms reported in patients living with SLE. We aim to: 1) determine if different trajectories of fatigue associate with specific latent classes of disease activity and 2) define the patient characteristics and associated factors in different latent classes. METHODS: Data from an inception cohort of adult patients from the Toronto Lupus Clinic from 1997-2018 were analyzed. Fatigue levels were measured using Fatigue Severity Scale (FSS) and disease activity by the Adjusted Mean Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) (AMS). Dual latent class trajectory analysis, for fatigue and AMS, was performed. Univariable and multivariable logistic regression analyses assessed the association of baseline variables with class membership. RESULTS: Among 280 patients, 4 dual classes (C) of fatigue and disease activity were identified: C1- lowest disease activity and second highest fatigue trajectory (27%); C2- second highest disease activity and highest fatigue trajectory (30%); C3-moderate disease activity and lowest fatigue trajectory (33%); and C4- highest disease activity and moderate fatigue trajectory (10%). CONCLUSION: 4 distinct latent classes of dual fatigue and disease activity trajectories were identified. Fatigue and disease activity follow distinct trajectories and disease activity alone cannot fully explain fatigue trajectories. Trajectories with higher FSS scores were associated with more fibromyalgia and trajectories with higher disease activity were associated with higher cumulative glucocorticoid use. Higher baseline glucocorticoid use was more likely associated with more fatigue while older age at SLE diagnosis was associated with less fatigue.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33483129

RESUMO

BACKGROUND: Underreporting of harms in randomized controlled trials (RCTs) may lead to incomplete or erroneous assessments of the perceived benefit-to-harm profile of an intervention. To compare benefit with harm in clinical practice and future clinical studies, adverse event (AE) profiles including severity need to be understood. Even though patients report harm symptoms earlier and more frequently than clinicians, rheumatology RCTs currently do not provide a reporting framework from the patient's perspective regarding harms. Our objective for this meta-research project was to identify AEs in order to determine harm clusters and whether these could be self-reported by patients. Our other objective was to examine reported severity grading of the reported harms. METHODS: We considered primary publications of RCTs eligible if they were published between 2008 and 2018 evaluating pharmacological interventions in patients with a rheumatic or musculoskeletal condition and if they were included in Cochrane reviews. We extracted data on harms such as reported AE terms together with severity (if described), and categorized AE- and severity-terms into overall groups. We deemed all AEs with felt components appropriate for patient self-reporting. RESULTS: The literature search identified 187 possible Cochrane reviews, of which 94 were eligible for evaluation, comprising 1,297 articles on individual RCTs. Of these RCTs, 93 pharmacological trials met our inclusion criteria (including 31,023 patients; representing 20,844 accumulated patient years), which reported a total of 21,498 AEs, corresponding to 693 unique reported terms for AEs. We further sub-categorized these terms into 280 harm clusters (i.e., themes). AEs appropriate for patient self-reporting accounted for 58% of the AEs reported. Among the reported AEs, we identified medical terms for all of the 117 harm clusters appropriate for patient reporting and lay language terms for 86%. We intended to include severity grades of the reported AEs, but there was no evidence for systematic reporting of clinician- or patient-reported severity in the primary articles of the 93 trials. However, we identified 33 terms suggesting severity, but severity grading was discernible in only 9%, precluding a breakdown by severity in this systematic review. CONCLUSIONS: Our results support the need for a standardized framework for patients' reporting of harms in rheumatology trials. Reporting of AEs with severity should be included in future reporting of harms, both from the patients' and investigators' perspectives. REGISTRATION: PROSPERO: CRD42018108393.

9.
RMD Open ; 7(1)2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33452180

RESUMO

OBJECTIVES: We examined patient-reported outcomes (PROs) in The Study of Etanercept And Methotrexate in Patients with Psoriatic Arthritis (PsA); a 48-week, phase 3, randomised controlled trial that compared outcomes with methotrexate (MTX) monotherapy, etanercept monotherapy, and MTX+ etanercept in patients with PsA. METHODS: Efficacy endpoints included: mean changes from baseline and proportion of patients who reported improvements≥minimal clinically important difference (MCID) at week 24 in treatment groups for Health Assessment Questionnaire-Disability Index, Patient Global Assessment (PtGA), Patient Global Assessment of Joint Pain (PtGAJP) and Medical Outcomes Study Short Form-36 Questionnaire (SF-36) Physical Component Summary (PCS), and Mental Component Summary, and eight domain scores. PROs were analysed as reported (observed), without multiplicity adjustment; therefore, p values are descriptive. RESULTS: At week 24, patients receiving etanercept monotherapy or MTX+ etanercept combination reported greater improvements (p≤0.05) in PtGA, PtGAJP and SF-36 PCS scores compared with those receiving MTX monotherapy. Compared with MTX monotherapy, higher proportions of patients receiving etanercept monotherapy and combination therapy reported improvements≥MCID in PtGA (etanercept vs MTX, p=0.005) and PtGAJP (MTX +etanercept vs MTX, p=0.038). Across PROs, proportions of patients reporting scores≥age and gender-matched normative values at week 24 ranged from 20.8% to 51.0% with MTX monotherapy, 30.9% to 48.8% with etanercept monotherapy, and 30.6% to 52.3% with MTX+ etanercept combination. CONCLUSIONS: Patients receiving etanercept monotherapy or MTX+ etanercept reported greater improvements from baseline in several PROs compared with those receiving MTX monotherapy. PROs should be incorporated in discussions between patients and clinicians regarding their treatment choices as they can help determine which treatments are more beneficial in patients with PsA.

10.
Clin Rheumatol ; 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33411137

RESUMO

The interferon (IFN) pathway, especially type I IFN, plays a critical role in the immunopathogenesis of systemic lupus erythematosus (SLE). We have gained significant insights into this pathway over the past two decades, including a better understanding of the key mediators of inflammation upstream and downstream of type I IFN. This has led to the identification of multiple potential targets for the treatment of SLE, for which a significant unmet need remains due to the failure of many patients to adequately respond to standard-of-care medications. Unfortunately, most new therapies in SLE have disappointed in preclinical or clinical trials to date, including a number that target type I IFN. Nevertheless, several IFN-directed therapies aimed at specific steps within this immunologic pathway have recently shown promise, and additional agents are in the treatment pipeline. In this review, we focus on the results of key therapeutic studies targeting the type I IFN pathway and discuss the future state of IFN-blockade in SLE.

11.
Nat Rev Rheumatol ; 17(2): 81-97, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33318665

RESUMO

Biologic agents have become a core component of therapeutic strategies for many inflammatory rheumatic diseases. However, perhaps reflecting the specificity and generally high affinity of biologic agents, these therapeutics have been used by rheumatologists with less consideration of their pharmacokinetics than that of conventional synthetic DMARDs. Immunogenicity was recognized as a potential limitation to the use of biologic agents at an early stage in their development, although regulatory guidance was relatively limited and assays to measure immunogenicity were less sophisticated than today. The advent of biosimilars has sparked a renewed interest in immunogenicity that has resulted in the development of increasingly sensitive assays, an enhanced appreciation of the pharmacokinetic consequences of immunogenicity and the development of comprehensive and specific guidance from regulatory authorities. As a result, rheumatologists have a greatly improved understanding of the field in general, including the factors responsible for immunogenicity, its potential clinical consequences and the implications for everyday treatment. In some specialties, immunogenicity testing is becoming a part of routine clinical management, but definitive evidence of its cost-effectiveness in rheumatology is awaited.


Assuntos
Imunidade Adaptativa/efeitos dos fármacos , Fatores Biológicos/farmacocinética , Doenças Reumáticas/tratamento farmacológico , Reumatologia/normas , Imunidade Adaptativa/imunologia , Antirreumáticos/administração & dosagem , Antirreumáticos/uso terapêutico , Fatores Biológicos/imunologia , Fatores Biológicos/uso terapêutico , Medicamentos Biossimilares/farmacocinética , Medicamentos Biossimilares/uso terapêutico , Análise Custo-Benefício , Humanos , Doenças Reumáticas/imunologia , Reumatologistas/estatística & dados numéricos , Reumatologia/economia
12.
Rheumatol Ther ; 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33284423

RESUMO

INTRODUCTION: Ixekizumab, an interleukin-17A antibody, has shown efficacy in non-radiographic axial spondyloarthritis (nr-axSpA). The objectives of this analysis were (a) to measure improvement in ixekizumab-treated patients in Assessment of Spondyloarthritis International Society (ASAS) response domains and other patient-reported outcomes (PROs) and (b) to determine how ASAS responses were associated with changes in patient global disease activity (PtGA), spinal pain, function, stiffness, fatigue, and spinal pain at night. METHODS: COAST-X was a phase 3, 52-week multicenter, randomized, controlled trial investigating the efficacy and safety of 80-mg ixekizumab every 2 weeks (Q2W) and every 4 weeks (Q4W) in patients with active nr-axSpA. Changes from baseline in PROs were analyzed via mixed-effects models for repeated measures. Association analyses for ASAS responses used analysis of covariance with Scheffé's method. RESULTS: Patients treated with ixekizumab Q2W and Q4W reported significantly greater improvements in PtGA, spinal pain, function, and stiffness at week 1, when these measures were first assessed, compared with placebo (p < 0.05). ASAS40 responders, in comparison to ASAS20 non-responders, had the highest correlations with improvements in all response domains (PtGA, spinal pain, function, and stiffness) as well as fatigue and spinal pain at night (p < 0.001). ASAS40 responses were associated with 3.5- to 48.0-fold greater improvements in these PROs, with the highest values for PtGA and function, compared to ASAS20 non-achievement. CONCLUSIONS: As early as week 1, patients with nr-axSpA treated with ixekizumab reported significant improvements in PtGA, spinal pain, function, and stiffness compared with those taking placebo. ASAS40 responders reported significantly greater improvements in all ASAS response domains (PtGA, spinal pain, function, and stiffness) as well as fatigue and spinal pain at night than ASAS20 non-responders. Improvements in PtGA and function appear to be major drivers in achieving ASAS40 response in patients with nr-axSpA. TRIAL REGISTRATION: NCT02757352.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33313898

RESUMO

OBJECTIVE: To evaluate the effect of upadacitinib (UPA) monotherapy vs MTX on patient-reported outcomes (PROs) in patients with RA who were MTX-naïve or who had an inadequate response to MTX (MTX-IR). METHODS: PROs from the SELECT-EARLY and SELECT-MONOTHERAPY randomized controlled trials were evaluated at Weeks 2 and 12/14. Patients were ≥18 years of age with RA symptoms for ≥6 weeks (SELECT-EARLY, MTX-naïve) or diagnosed RA for ≥3 months (SELECT-MONOTHERAPY, MTX-IR) and received UPA monotherapy (15 or 30 mg) or MTX. PROs included Patient Global Assessment of Disease Activity (PtGA), pain visual analogue scale, HAQ Disability Index (HAQ-DI), morning stiffness duration/severity, Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue (SELECT-EARLY), health-related quality of life (HRQOL) by the 36-iem Short Form Health Survey and Work Productivity and Activity Impairment (WPAI; SELECT-EARLY). Least square mean (LSM) changes and proportions of patients reporting improvements greater than or equal to the minimum clinically important differences and normative values were determined. RESULTS: In 945 MTX-naïve and 648 MTX-IR patients, UPA monotherapy (15 mg, 30 mg) vs MTX resulted in greater reported LSM changes from baseline at Weeks 12/14 in PtGA, pain, HAQ-DI, morning stiffness duration/severity, FACIT-F (SELECT-EARLY), HRQOL and WPAI (SELECT-EARLY). These changes were statistically significant with both doses of UPA vs MTX at Weeks 12/14 in both RCTs. Improvements were reported as early as week 2. Compared with MTX, more UPA-treated MTX-naïve and MTX-IR patients reported improvements greater than or equal to the minimum clinically important differences and scores greater than or equal to normative values. CONCLUSION: Among MTX-naïve and MTX-IR patients with active RA, UPA monotherapy at 15 or 30 mg for 12/14 weeks resulted in statistically significant and clinically meaningful improvements in pain, physical function, morning stiffness, HRQOL and WPAI compared with MTX alone. CLINICAL TRIAL REGISTRATION NUMBER: SELECT-EARLY (NCT02706873) and SELECT-MONOTHERAPY (NCT02706951) are registered with ClinicalTrials.gov.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33227175

RESUMO

OBJECTIVE: To investigate the longer-term effects of secukinumab 150 mg on fatigue in patients with ankylosing spondylitis (AS) in MEASURE 1 (up to 3 years) and MEASURE 2 (up to 2 years). METHODS: Patients with active AS were randomized to secukinumab or placebo in MEASURE 1 (10 mg/kg intravenous [IV] followed by 150 mg subcutaneous [SC]) and MEASURE 2 (150 mg SC). Patients were naive to or had an inadequate response/intolerance to tumor necrosis factor inhibitors (anti-TNF-naive/ anti-TNF-IR). Fatigue was measured using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale. Relationships between fatigue response and baseline characteristics and clinical/laboratory variables were explored. RESULTS: Significant improvements in FACIT-F scores from baseline were observed with secukinumab across both studies versus placebo at week 16 (P < 0.05). Improvements were sustained through week 156 (MEASURE 1)/week 104 (MEASURE 2). Significantly more patients reported fatigue responses (FACIT-F increase ≥4; observed data) with secukinumab 150 mg than placebo at week 16 in both MEASURE 1 (P < 0.05) and MEASURE 2 (P < 0.01). Fatigue responses were achieved by 75.6% of patients receiving secukinumab at week 156 (MEASURE 1) and 81.4% at week 104 (MEASURE 2); these results were consistent in both anti-TNF-naive (74.3% and 84.6%) and anti-TNF-IR (81.3% and 75.0%) patients. Baseline characteristics did not predict improvement in fatigue consistently. Fatigue responses were moderately to strongly correlated with responses in several clinical measures, including Assessment of SpondyloArthritis international Society (ASAS)20/40, ASAS5/6 responses, Ankylosing Spondylitis Disease Activity Score-C reactive protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Short-form (SF)-36 scores. CONCLUSION: Secukinumab provided rapid and sustained improvements in fatigue for up to 3 years, regardless of prior anti-TNF exposure.

15.
J Rheumatol ; 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-33191280

RESUMO

OBJECTIVE: The objective of this population-based cohort study was to investigate the association of fatigue with disease activity and drug survival in PsA patients receiving their first tumor necrosis factor inhibitor (TNFi). METHODS: Data on patient characteristics, disease activity and drug survival were obtained from the DANBIO database on all PsA patients in the period 2006 through 2015. Information on comorbidities was obtained through linkage with the Danish National Patient Registry. RESULTS: A total of 880 patients were eligible for analyses. Patients with upper median fatigue scores had statistically significant higher disease activity measure (DAS28CRP), pain and health assessment questionnaire (HAQ) scores, tender joint count, comorbidities (Charlson Comorbidity Index ≥2) and current smoking status at baseline compared to patients with lower median fatigue scores (p<0.05). In the upper median fatigue group, less patients achieved ACR responses and improvements in VAS fatigue compared to patients in the lower median fatigue group. Kaplan-Meier curves showed shorter drug survival in patients in the upper median fatigue group compared with the lower median fatigue group at 6-month followup. CONCLUSION: Fatigue remains a dominating symptom after TNFi treatment, and is associated with higher baseline disease activity, pain and HAQ scores, more comorbidities, and increased risk of TNFi treatment discontinuation in a cohort of Danish patients with PsA. The agreement between ACR and VAS fatigue responses is weak to moderate suggesting heterogeneity between experienced fatigue and joint inflammation.

16.
Mod Rheumatol ; : 1-22, 2020 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-33164611

RESUMO

OBJECTIVE: To assess upadacitinib monotherapy versus methotrexate (MTX) in MTX-naïve Japanese patients with rheumatoid arthritis (RA) from the Phase 3 SELECT-EARLY study. METHODS: Japanese patients were randomized 2:1:1:1 to upadacitinib 7.5, 15, or 30 mg daily or MTX 7.5 mg/week (titrated to ≤15 mg/week). Efficacy endpoints included the proportion of patients reporting 20% improvement in American College of Rheumatology criteria (ACR20) at week 12 and change from baseline in modified Total Sharp Score (mTSS) at week 24. Other efficacy outcomes were also assessed at weeks 12 and/or 24. Safety was assessed over 24 weeks. RESULTS: Of 138 Japanese patients enrolled, significantly more patients treated with upadacitinib 7.5 and 15 mg, but not 30 mg, reported ACR20 responses versus MTX at week 12. Significantly smaller changes from baseline in mTSS were observed with upadacitinib 15 and 30 mg, but not 7.5 mg, versus MTX at week 24. Upadacitinib demonstrated an acceptable safety profile; herpes zoster occurred in 3.6%, 7.4%, and 7.1% of patients treated with upadacitinib 7.5, 15, and 30 mg, respectively. CONCLUSION: Similar to the global study population, upadacitinib demonstrated clinical efficacy superior to placebo in the Japanese subpopulation. Among upadacitinib-treated patients, herpes zoster was least common with 7.5 mg.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33129886

RESUMO

Autoimmune and inflammatory diseases are common, diverse, and they can affect nearly any organ system. Much of the pathogenesis of these diseases relates to dysregulated cytokine secretion. Historically, autoimmune and inflammatory diseases have been treated with medications that non-specifically suppress the immune system. Monoclonal antibodies that block the action of pathogenic cytokines emerged two decades ago and have become widely useful. More recently, agents that simultaneously block multiple pathogenic cytokines via inhibition of the downstream Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway have emerged and are becoming increasingly important. These targeted synthetic drugs, collectively termed JAK inhibitors, are FDA approved in a few autoimmune disorders and are being evaluated in many others. Here we review the biology of the JAK-STAT pathway and the use of JAK inhibitors to treat autoimmunity across medical subspecialties.

18.
Artigo em Inglês | MEDLINE | ID: mdl-33044756

RESUMO

OBJECTIVE: To evaluate the effect of ixekizumab on self-reported functioning and health in patients with active non-radiographic axial spondyloarthritis (nr-axSpA). METHODS: COAST-X is a randomized, controlled trial conducted in patients with nr-axSpA of 52-weeks duration. Participants were randomized 1:1:1 to receive subcutaneous 80 mg ixekizumab every 4 weeks (Q4W) or every 2 weeks (Q2W), or placebo for 52 Weeks. Self-reported functioning and health endpoints included the Medical Outcomes Study 36-Item Short Form Health Survey 36-item (SF-36), Assessment of SpondyloArthritis international Society Health Index (ASAS HI), and European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) health-utility. RESULTS: Compared with placebo, ixekizumab treatment improved SF-36 Physical Component Summary scores from baseline (4.7 versus 8.9 IXE Q4W, p<0.05, 9.3 IXE Q2W, p<0.01), with greatest improvements observed in Physical Functioning, Role-physical and Bodily Pain domains at Weeks 16 and 52. Higher proportion of patients receiving ixekizumab reported ASAS HI improvements ≥3 from baseline at Weeks 16 (Q2W, p<0.05) and 52 (p<0.05). Significantly more patients on ixekizumab reported improvements in ASAS HI "good health status" (ASAS HI ≤5) at Weeks 16 (Q4W, p<0.05) and 52 (p<0.05). Patients on ixekizumab reported improvements in EQ-5D-5L versus placebo at Week 16 (0.11 versus 0.17 Q4W, 0.19 Q2W, p<0.05), which remained consistent at Week 52. There were no clinical meaningful differences in responses based on the ixekizumab dosing regimen (Q2W or Q4W). CONCLUSION: Ixekizumab was superior to placebo improving self-reported functioning and health in patients with nr-axSpA at Weeks 16 and 52.

19.
Arthritis Res Ther ; 22(1): 250, 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-33081825

RESUMO

BACKGROUND: Increased levels of cytokines, including interleukin-6 (IL-6), reflect inflammation and have been shown to be predictive of therapeutic responses, fatigue, pain, and depression in patients with rheumatoid arthritis (RA), but limited data exist on associations between IL-6 levels and health-related quality of life (HRQoL). This post hoc analysis of MONARCH phase III randomized controlled trial data evaluated the potential of baseline IL-6 levels to differentially predict HRQoL improvements with sarilumab, a fully human monoclonal antibody directed against both soluble and membrane-bound IL-6 receptor α (anti-IL-6Rα) versus adalimumab, a tumor necrosis factor α inhibitor, both approved for treatment of active RA. METHODS: Baseline serum IL-6 levels in 300/369 randomized patients were categorized into low (1.6-7.1 pg/mL), medium (7.2-39.5 pg/mL), and high (39.6-692.3 pg/mL) tertiles. HRQoL was measured at baseline and week (W)24 and W52 by Short Form 36 (SF-36) physical/mental component summary (PCS/MCS) and domain scores, Functional Assessment of Chronic Illness Therapy -fatigue, and duration of morning stiffness visual analog scale (AM-stiffness VAS). Linear regression of changes from baseline in HRQoL (IL-6 tertile, treatment, region as a stratification factor, and IL-6 tertile-by-treatment interaction as fixed effects) assessed predictivity of baseline IL-6 levels, with low tertile as reference. Pairwise comparisons of improvements between treatment groups were performed by tertile; least squares mean differences and 95% CIs were calculated. Similar analyses evaluated W24 patient-level response on minimum clinically important differences (MCID). RESULTS: At baseline, patients with high versus medium or low IL-6 levels (n = 100, respectively) reported worse (nominal p < 0.05) SF-36 MCS and role-physical, bodily pain, social functioning, role-emotional domain, and AM-stiffness VAS scores. There was a greater treatment effect with sarilumab versus adalimumab in high tertile versus low tertile groups in SF-36 PCS, physical functioning domain, and AM-stiffness VAS (nominal interaction p < 0.05). PCS improvements ≥MCID were higher in high (odds ratio [OR] 6.31 [2.37, 16.81]) versus low (OR 0.97 [0.43, 2.16]) tertiles with sarilumab versus adalimumab (nominal interaction p < 0.05). Adverse events between IL-6 tertiles were similar. CONCLUSIONS: Patients with high baseline IL-6 levels reported better improvements in PCS, physical functioning domain, and AM-stiffness scores with sarilumab versus adalimumab and safety consistent with IL-6R blockade. TRIAL REGISTRATION: NCT02332590 . Registered on 5 January 2015.

20.
Arthritis Res Ther ; 22(1): 243, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33059710

RESUMO

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We examined the degree to which Patient Global Assessment of Disease Activity (PtGA) was driven by patient-reported assessments of pain (Pain), physical function, and fatigue in patients receiving tofacitinib 5 mg twice daily or placebo, each with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). METHODS: This post hoc analysis used data pooled from three randomized controlled trials in csDMARD-inadequate responder (csDMARD-IR) patients (ORAL Scan: NCT00847613; ORAL Standard: NCT00853385; ORAL Sync: NCT00856544). Using subgroup analysis from 2 × 2 tables, associations between PtGA and Pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at month 3 were evaluated using Pearson's Phi correlation coefficients. To support the main analysis, associations between select patient-reported outcomes (PROs) were also evaluated in csDMARD-naïve (ORAL Start; NCT01039688) and biologic (b)DMARD-IR (ORAL Step; NCT00960440) patients. RESULTS: Across csDMARD-IR treatment groups, low disease activity (defined as PtGA ≤ 20 mm), and moderate (≥ 30%) and substantial (≥ 50%) improvements from baseline in PtGA were associated with mild Pain (Visual Analog Scale score ≤ 20 mm), and moderate (≥ 30%) and substantial (≥ 50%) improvements from baseline in Pain; lack of Pain improvement was associated with little/no improvement in PtGA. In contrast, large proportions of csDMARD-IR patients who reported PtGA improvements did not report HAQ-DI or FACIT-F scores ≥ normative values (≤ 0.25 and ≥ 43.5, respectively) or changes in HAQ-DI or FACIT-F scores ≥ minimum clinically important difference (≥ 0.22 and ≥ 4.0, respectively). Generally, PtGA and Pain outcomes were moderately-to-strongly correlated at month 3 in csDMARD-IR patients, with weaker correlations evident between PtGA and HAQ-DI/FACIT-F outcomes. Similar findings were generally evident in csDMARD-naïve and bDMARD-IR patients. CONCLUSIONS: This analysis supports the role of Pain as a key driver of PtGA in RA; physical function and fatigue play lesser roles in patients' perceptions of disease activity. These findings corroborate the importance of improved PROs and attainment of low symptom states for optimizing patient care. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00847613 (registered: February 19, 2009); NCT00853385 (registered: March 2, 2009); NCT00856544 (registered: March 5, 2009); NCT01039688 (registered: December 25, 2009); NCT00960440 (registered: August 17, 2009).

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