Ixekizumab improves spinal pain, function, fatigue, stiffness, and sleep in radiographic axial Spondyloarthritis: COAST-V/W 52-week results

Background This analysis assessed improvements in patients with radiographic axial spondyloarthritis (r-axSpA) treated with ixekizumab in the Assessment of Spondyloarthritis International Society (ASAS) treatment response domains and additional patient-reported outcomes at 1 year of treatment. Methods COAST-V and COAST-W were 52-week, phase 3, randomized controlled trials evaluating the efficacy and safety of ixekizumab in biologic disease-modifying antirheumatic drug (bDMARD)-naïve and tumor necrosis factor inhibitor (TNFi)-experienced patients with radiographic spondyloarthritis, respectively. Patients were treated with 80-mg ixekizumab either every 2 weeks or every 4 weeks. Patient-reported outcomes included Patient Global Disease Activity, Spinal Pain, stiffness as measured by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Questions 5 and 6, function as measured by the Bath Ankylosing Spondylitis Functional Index, fatigue as measured by the Fatigue Numeric Rating Scale and BASDAI question 1, Spinal Pain at Night, and sleep quality as measured by the Jenkins Sleep Evaluation Questionnaire. Mixed-effects models for repeated measures were used to analyze changes from baseline in patient-reported outcomes from weeks 1 to 16, and descriptive statistics were reported from weeks 20 to 52. Analysis of covariance with Scheffé’s method was used for the ASAS response association analyses. Results This study assessed 341 bDMARD-naïve and 316 TNFi-experienced patients in the placebo-controlled blinded treatment dosing period (weeks 1–16) as well as 329 bDMARD-naïve and 281 TNFi-experienced patients in the dose double-blind extended treatment period (weeks 20–52). bDMARD-naïve or TNFi-experienced patients treated with ixekizumab every 2 weeks and every 4 weeks reported improvements in patient global disease activity, spinal pain, function, stiffness, fatigue, spinal pain at night, and sleep quality through week 52. Greater correlations with improvements in all response domains were seen when comparing ASAS40 responders to ASAS20 non-responders (p < 0.001), with up to 10.5-fold greater improvements observed in ASAS40 responses compared with ASAS20 non-responders. Function and fatigue demonstrated the highest values. Conclusions Ixekizumab-treated bDMARD-naïve and TNFi-experienced patients with radiographic axial spondyloarthritis achieving ASAS40 reported sustained and consistent improvement in all ASAS response domains and other patient-reported outcomes though week 52, with spinal pain, function, and stiffness as major drivers of the response. Trial registration NCT02696785 and NCT02696798, March 2, 2016.

Consumer-based activity trackers in evaluation of physical activity in myositis patients

Objectives Inflammatory myopathies are characterized by muscle weakness that limits the activities of daily living. Daily step count is an accepted metric of physical activity. Wearable technologies such as Fitbit® enable tracking of daily step counts. We assessed the psychometric properties of Fitbit® and compared the accuracy of Fitbit® step counts to ActiGraph®. Methods This was a pilot, proof of concept, prospective observational study with four visits at 0, 1, 3 and 6 months in PM, DM, necrotizing myopathy (NM) or anti-synthetase syndrome (AS) subjects. Six core set measures (manual muscle testing, physician global disease activity, patient global disease activity, and extra-muscular disease activity, HAQ-Disability Index and creatine kinase), three functional tests (six-min walk, timed up-and-go, sit-to-stand tests) and SF-36 physical function-10 (PF10) were collected at each visit. Patients wore waist-worn Fitbit® One and ActiGraph® T3X-BT concurrently for 7 days/month for 6 months. Results Twenty-four (10 DM, 8 PM/NM, 6 AS) patients (17 females/7 males; 91% Caucasian) were enrolled. Test-retest reliability of daily steps was strong in 1-month follow-up (ICC 0.89). Daily steps and peak 1-min cadence showed moderate-strong correlations with physician global disease activity, patient global disease activity, HAQ-Disability Index, SF-36 PF10 and all three functional tests. Fitbit® and ActiGraph® step counts demonstrated good agreement and strong correlation (ICC 0.96). Conclusion Fitbit® daily steps and peak 1-min cadence are reliable and valid measures of physical activity in a cohort of myositis patients. This pilot data suggests that Fitbit® has a potential for use in clinical practice and trials to monitor physical activity in myositis patients, but larger studies are needed for further validation.

Nailfold Capillaroscopy Abnormalities Correlate With Disease Activity in Adult Dermatomyositis

Objectives: The aim of this study was to determine the relationship between disease activity in adult patients with dermatomyositis (DM) and other biomarkers of disease activity such as C-reactive protein creatinine kinase and nailfold video capillaroscopy (NVC).Methods: We performed a prospective single center study of 15 adult patients with DM. Study participants underwent two assessments at least 9 months apart including clinical, laboratory and NVC evaluations. Patients received immunosuppressive medications for their dermatomyositis, and ongoing disease activity was measured by the Myositis Intention to Treat Index (MITAX). NVC evaluation included assessment of capillary density, capillary apical diameter (mm), and the number of microhemorrhages per digit.Results: Microvascular abnormalities were present in most DM patients. Of these, capillary density (4.71 vs. 6.84, p = 0.006) and mean apical diameter (56.09 vs. 27.79 μm, p = 0.003) significantly improved over the study period in concordance with improving disease control (MITAX 8.53 vs. 2.64, p = 0.002). Longitudinal analysis demonstrated that capillary density was independently associated with MITAX (β = −1.49 [CI −2.49, −0.33], p = 0.013), but not other parameters such as C-reactive protein and creatinine kinase.Conclusions: Nailfold capillary density is a dynamic marker of global disease activity in adult DM. NVC may be utilized as a non-invasive point-of-care tool to monitor disease activity and inform treatment decisions in patients with DM.

Is the fluorescence optical imaging (FOI) able to discriminate between rheumatoid arthritis patients with and without need of rituximab retherapy? A cohort study

ObjectiveTo evaluate the ability of fluorescence optical imaging (FOI) Xiralite in the discrimination between rheumatoid arthritis (RA) patients with and without need of rituximab (RTX) retherapy—in comparison to clinical, laboratory and musculoskeletal ultrasound parameters.Patients and methodsPatients with established RA were prospectively followed over 1 year by Disease Activity Score 28, patient’s global disease activity (visual analogue scale 0–100 mm), C reactive protein and erythrocyte sedimentation rate, ultrasound seven joint (US7) score and FOI in phases 1–3 and automatically generated PrimaVista mode (PVM) at baseline (before RTX) and after 3, 6 and 12 months. The need for RTX retherapy was decided by the treating rheumatologist—blinded to imaging data.Results31 patients (female 77.4%, mean age 60.1±11.4, mean disease duration 14.9±7.1 years) were included. Fourteen (45.2%) patients received RTX retherapy within 12 months. In the group with RTX retherapy, FOI in PVM mode was the only parameter that presented significant increase over time (β: 0.40, 95% CI: 0.08 to 0.71, p=0.013)—compared with the group without retherapy. In the prediction model via ROC analysis, FOI in PVM reached the highest values of all imaging, clinical and laboratory parameters which was associated with retherapy over 1 year with an area under the curve (AUC) of 0.78 (OR: 0.84, 95% CI: 0.72 to 0.98, p=0.031). US7 GS synovitis score revealed similar association with an AUC of 0.73 (p=0.049).ConclusionUS7 GS synovitis score and FOI in PVM are able to discriminate between patients with and without need for RTX retherapy better than clinical and laboratory parameters.

Development of an instrument for patient self-assessment in psoriatic arthritis

Objective Due to the recent pandemic, in person scheduled rheumatology appointments in many countries have been reserved for urgent cases only. Here we report the development of a multidimensional, patient completed disease assessment tool for use in psoriatic arthritis (PsA). Methods A focus group development and education method was used, followed by a paired observation design to assess feasibility and validity. The psoriatic arthritis disease activity score (PASDAS) was used as the basis for the clinical assessments but elements of this tool were modified during the focus group sessions. Results A preliminary tool assessed tender and swollen joint counts, enthesitis, dactylitis, area of skin involved by psoriasis, and scores for global disease activity, fatigue and spinal pain. In parallel assessments good agreement was found between subject and health professional assessors, though overall disease activity was low. Conclusion A self-assessment tool for disease activity in psoriatic arthritis has been developed in conjunction with patients demonstrating generally good agreement between patients and health professionals but more validation work is needed before it can be recommended for clinical practice.

Quick Systemic Lupus Activity Questionnaire (Q-SLAQ): a simplified version of SLAQ for patient-reported disease activity

ObjectivesMost indices of disease activity in SLE combine physicians’ assessments and laboratory tests. However, there is also a need to capture patients’ perspectives of disease activity. Consequently, we need new, preferably quick and easy instruments to collect this information, which can be very useful for online consultations and registry purposes. We compared patients’ assessments of SLE disease impact/activity, as reported by a shorter version of the Quick Systemic Lupus Activity Questionnaire (Q-SLAQ), with physicians’ assessments using SLE Activity Measure (SLAM) and SLE Disease Activity Index (SLEDAI-2K) and with the original Systemic Lupus Activity Questionnaire (SLAQ).MethodsPatients with SLE (n=115), with a disease duration of 15 years (IQR 17), completed the Q-SLAQ prior to physicians’ assessments by SLAM and SLEDAI-2K. A second set of patients (n=85) with similar characteristics filled out Q-SLAQ and SLAQ. Spearman’s ρ correlations were explored between patients’ total Q-SLAQ and subscales (Symptom Score, Patient’s Global Disease Activity) and physicians’ SLAM and SLEDAI-2K, with and without laboratory items (SLAM-nolab and SLEDAI-2K-nolab) and SLAQ. Corresponding items in Q-SLAQ and SLAM were compared.ResultsCorrelations between patients’ and physicians’ assessments were higher for SLAM-nolab (total Q-SLAQ, ρ=0.71; Symptom Score, ρ=0.67; and Patient’s Global Disease Activity, ρ=0.68) than for the original SLAM (total Q-SLAQ, ρ=0.53; Symptom Score, ρ=0.50; and Patient’s Global Disease Activity, ρ=0.53). Regarding specific symptoms, fatigue (ρ=0.72) and alopecia (ρ=0.71) correlated best, while pulmonary/respiratory symptoms correlated least (ρ=0.19, p=0.039). Physicians assessment with SLEDAI-2K-nolab correlated weakly with patients’ assessments (total Q-SLAQ, ρ=0.30; Symptom Score, ρ=0.30; and Patient’s Global Disease Activity, ρ=0.36). Bivariate correlations between Q-SLAQ and SLAQ were good (ρ=0.82–0.96).ConclusionsQ-SLAQ and the original SLAQ performed equally well, demonstrating that the shorter Q-SLAQ can safely be used to monitor patients’ perception of disease impact/activity. We also noted an intriguing discrepancy between physicians’ and patients’ evaluations of pulmonary/respiratory symptoms, which requires further investigations.

Reliability, Validity and Responsiveness of Physical Activity Monitors in Patients with Inflammatory Myopathy

Objective Idiopathic inflammatory myopathies (IIM) cause proximal muscle weakness, which affect activities of daily living. Wearable physical activity monitors (PAMs) objectively assess continuous activity with potential clinical usefulness in IIM assessment. We examined the psychometric characteristics for PAM outcomes in IIM. Methods Adult IIM patients were prospectively evaluated (baseline, 3 and 6-months) in an observational study. A waist-worn PAM (ActiGraph GT3X-BT) assessed average step counts/min, peak 1-min cadence, and vector magnitude/min. Validated myositis core set measures (CSM) including manual muscle testing (MMT), physician global disease activity (MD global), patient global disease activity (Pt global), extra-muscular disease activity (Ex-muscular global), HAQ-DI, muscle enzymes, and patient-reported physical function were evaluated. Test-retest reliability, construct validity, and responsiveness were determined for PAM measures and CSM using Pearson correlations and other appropriate analyses. Results 50 adult IIM patients enrolled [mean (SD) age, 53.6 (±14.6); 60% female, 94% Caucasian]. PAM measures showed strong test-retest reliability, moderate-to-strong correlations at baseline with MD global (r=-0.37- -0.48), Pt-global (r=-0.43- -0.61), HAQ-DI (r=-0.47- -0.59) and MMT (r = 0.37–0.52), and strong discriminant validity for categorical MMT and HAQ-DI. Longitudinal association with MD global (r=-0.38- -0.44), MMT (r = 0.50–0.57), HAQ-DI (r=-0.45- -0.55), and functional tests (r = 0.30–0.65) were moderate-to-strong. PAM measures were responsive to MMT improvement (≥10%) and moderate-to-major improvement on ACR/EULAR myositis response criteria. Peak 1-min cadence had the largest effect size and Standardized Response Means (SRMs). Conclusion PAM measures showed promising construct validity, reliability, and longitudinal responsiveness; especially peak 1-min cadence. PAMs provide valid outcome measures for future use in IIM clinical trials.

Comparing the visual analogue scale (VAS) and the numerical rating scale (NRS) in patient reported outcomes in psoriatic arthritis

Objective Patient self-report scales are invaluable in psoriatic arthritis (PsA), as they allow physicians to rapidly assess patient perspectives of disease activity. We aimed to assess the agreement of the visual analogue scale (VAS), a 100 mm horizontal line, and the numerical rating scale (NRS), a 21-point scale ranging from 0 to 10 in increments of 0.5, in patients with PsA. Methods Data were collected prospectively across three UK hospital trusts from 2018-2019. All patients completed the VAS and NRS for pain, arthritis, skin psoriasis, and global disease activity. A subset completed an identical pack one week later. Demographic and clinical data were also collected. Agreement was assessed using medians and the Bland-Altman method. Intraclass correlation coefficients (ICC) were used to assess test-retest reliability. Spearman’s rank correlation coefficients were used to assess dependency between scale scores and clinical parameters. Results 210 patients completed the study; one withdrew consent, thus 209 were analysed. For pain, arthritis, skin psoriasis and global disease activity, the difference between the VAS and NRS mostly lay within 1.96 SD of the mean, suggesting reasonable agreement between the two scales. 64.1% patients preferred the NRS. The ICCs demonstrate excellent test-retest reliability for both VAS and NRS. Higher VAS and NRS scores were associated with increased tender/swollen joint count, poorer functional status and greater life impact. Conclusion The VAS and NRS show reasonable agreement in key patient reported outcomes in PsA. Results from both scales are correlated with disease severity and life impact.

Potential Differences in Clinical Features, Disease Activity, Function and Impact of Disease Between Oligo and Polyarticular Psoriatic Arthritis

Objective: The primary aim of the study was to assess the potential differences in clinical features, disease activity, function and impact of disease between Psoriatic Arthritis (PsA) patients with oligoarticular and polyarticular involvement. Methods: Consecutive PsA patients attending our unit were divided into 2 groups: 1) Oligoarticular (<5 involved joints with or without enthesitic/axial manifestations) and 2) Polyarticular (≥5 joints with or without enthesitic/axial manifestations). A full clinical examination with the assessment of disease characteristics, disease activity (DAPSA, MDA), function (HAQ-DI) and impact of disease (PsAID-12) was performed. Furthermore, a 6-month follow-up evaluation was carried out in order to assess disease differences at baseline and at follow-up. Results: Of the 102 enrolled patients, oligoarticular subset was present in 63 (61.7%), while 39 (38.3%) patients had polyarticular involvement. Patients with oligoarticular subset showed, at baseline evaluation, lower values of global disease activity assessed by physician, HAQ-DI and DAPSA compared to patients with polyarticular pattern. No differences in the impact of disease (PsAID), patient global assessment of disease activity or pain were found. At 6-month follow-up, no significant changes in each group occurred. Conclusion: Our study showed some differences in patients with oligoarticular and polyarticular involvement in terms of disease activity and HAQ-DI, while the overall impact of the disease and the presence of enthesitis, dactylitis and axial disease seem to be similar, with no substantial changes after 6-month follow-up. These results could mean that clinical phenotype might not be responsible for the impact of the disease perceived by the patient.