Exploring the Effects of Ixekizumab on Pain in Patients with Ankylosing Spondylitis Based on Objective Measures of Inflammation: Post Hoc Analysis from a Large Randomized Clinical Trial.

INTRODUCTION: The objective of this analysis is to evaluate the improvement in spinal pain with ixekizumab, placebo, and adalimumab based on objective measures of inflammation response in patients with ankylosing spondylitis (AS). METHODS: The COAST-V 52-week, double-blind, placebo-controlled, randomized phase III trial examined the efficacy of ixekizumab in patients with active AS; adalimumab was used as an active reference arm. Treatment effects on reduction in pain were assessed by objective measures of controlled and persisting inflammation (defined by magnetic resonance imaging [MRI], C-reactive protein [CRP], or MRI + CRP status). Pathway analysis was used to analyze treatment effect that was not attributable to reduction in inflammation biomarkers. RESULTS: In patients with AS, when inflammation was controlled as assessed by MRI, patients treated with ixekizumab experienced a reduction in spinal pain at night (SP-N, numeric rating scale, ixekizumab mean = - 3.9, p < 0.001, adalimumab mean = - 2.6, p < 0.05) compared to placebo (mean = - 1.6) at week 16. When inflammation was controlled as assessed by MRI + CRP, ixekizumab and adalimumab had numerically greater reductions at week 16 in SP-N versus placebo. All ixekizumab groups had further improvements at week 52. When inflammation was persisting as assessed by MRI + CRP, ixekizumab-treated patients had significant reduction in SP-N (mean = - 3.7, p < 0.001) versus placebo (mean = - 1.7), improvement with adalimumab did not reach significance (mean = - 2.6, p = 0.06). In the pathway analysis at week 16, ixekizumab had a greater effect on pain outcomes compared to adalimumab. CONCLUSION: This post hoc analysis is supportive of the hypothesis that ixekizumab reduces pain in AS by additional mechanisms other than the reduction of measurable inflammation. TRIAL REGISTRATION NUMBER: NCT02696785.

Effectiveness of bDMARDs in ankylosing spondylitis patients by biologic use: experience from the CorEvitas PsA/SpA Registry.

OBJECTIVE: To describe bDMARD initiators by biologic experience among ankylosing spondylitis (AS) patients and change in disease activity and patient-reported outcomes (PROs) in real-world US patients. METHODS: We included patients ≥18 years with AS based on physician diagnosis enrolled between 3/2013 and 11/2019 in the CorEvitas Psoriatic Arthritis (PSA)/Spondyloarthritis Registry (NCT02530268). Patients concurrently diagnosed with PSA were excluded. Baseline (bDMARD initiation) demographics, comorbidities, disease characteristics, treatment, and PROs were collected. Response rates and changes in disease activity and PROs between baseline and 6- and 12- month follow-up visits were calculated. RESULTS: Of the 489 AS patients in the PsA/SpA Registry, 254 AS (52.0%) patients initiated a bDMARD at enrollment or during follow-up (total initiations: AS = 313). Of the 313 AS initiations, 179 (57.2%) had a 6-month follow-up, 122 (39.0%) had a 12-month follow-up, and 94 (30.0%) had a 6- and 12-month follow-up visit. For those AS initiators with a 6-month follow-up, the mean age was 49.1 years, 44.4% were female, and 70.4%, 47.5%, 96.1%, and 46.9% had never used cDMARDs, TNFis, non-TNFis, and bDMARDs, respectively. Of these 179 AS initiators, 20.1% and 14.0% achieved ASAS20/40, respectively. Further, only 34% achieved low disease activity (ASDAS <2.1). When stratified by biologic-naivete and biologic-experience, the ASAS 20/40 achievement rates were 26.2% and 14.7%, and 21.4% and 7.4%, respectively, for this cohort. CONCLUSION: Although AS patients initiate bDMARDs, many do not achieve optimal treatment responses. Future research is needed to investigate the aspects associated with inadequate improvement and treatment response to bDMARDs.

Employment, Work Productivity, and Biologic Treatments in Self-Reported Axial Spondyloarthritis: a Cross-Sectional Study in a Female Predominant Population from the ArthritisPower Registry.

INTRODUCTION: The aim of this study was to characterize employment, work productivity, and biologic disease-modifying anti-rheumatic drug (bDMARD) treatment in a predominantly female population of axial spondyloarthritis (axSpA) patients in a real-world setting. METHODS: This was a cross-sectional study of axSpA participants within the ArthritisPower registry. Outcomes were assessed with surveys (Work Productivity and Activity Impairment [WPAI], Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], and Patient-Reported Outcomes Measurement Information System instruments) and compared between subgroups (employed vs. not employed; taking vs. not taking a bDMARD). RESULTS: Among the 195 participants, 117 (60.0%) were employed and 78 (40.0%) were not employed entirely or partially due to axSpA. The mean age of the participants was 47.6 years and 86.7% were female. Current bDMARD use was reported by 57.4% of those surveyed (59.8% employed vs. 53.9% not employed; p = 0.408). Compared to not employed participants, employed participants had more favorable disease activity (BASDAI 6.0 vs. 7.6; p < 0.001) and overall health (self-rated health 2.5 vs. 1.8; p < 0.001). Employed participants, compared to not employed participants, were diagnosed at an earlier age (36.0 vs. 42.5 years, respectively) and experienced a shorter time between symptom onset and diagnosis (9.5 vs. 13.6 years, respectively). Employed participants reported missing on average 6.5 days of work and experienced a 52.7% impairment on work productivity due to axSpA over a 3-month period. Absenteeism and presenteeism were statistically similar between participants taking a bDMARD versus those not taking a bDMARD. CONCLUSIONS: Although bDMARD treatment rates were similar between employed and not employed participants, disease activity and overall health were better in employed than non-employed participants. Employed participants experienced substantial work productivity impairment due to axSpA.

Patient Perspectives on Biologics for Axial Spondyloarthritis in a Cross-sectional Study in a Predominantly Female Population: Treatment Satisfaction, Wear-off Between Doses, and Use of Supplemental Medication.

INTRODUCTION: There is limited information regarding treatment experience of patients with axial spondyloarthritis/ankylosing spondylitis (axSpA/AS) receiving biological disease-modifying antirheumatic drugs (bDMARDs). Here we characterize patient experiences and perspectives, including satisfaction among those currently treated with bDMARD therapy for axSpA/AS. We also assess the use of supplemental medication during perceived wear-off between doses. METHODS: Adult participants from the United States within the ArthritisPower registry with physician-diagnosed axSpA/AS were invited to complete electronic patient-reported outcome measures and an online survey about their perspectives of treatment. Analysis compared patient characteristics and treatment satisfaction by whether wear-off in axSpA/AS between bDMARD doses was reported. RESULTS: Of 128 patients currently taking a DMARD, the mean age was 46.9 (10.3) years, 82.0% were female, and 93.8% were White. A total of 78 (60.9%) perceived wear-off with their current bDMARD before the next dose, 19 (14.8%) did not experience wear-off and 31 (24.2%) were unsure about wear-off. Mean (standard deviation [SD]) Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score indicated poor disease control in all patients receiving bDMARDs (6.4 [1.8]); worse for those perceiving wear-off between doses versus those who did not perceive wear-off or were unsure (6.8 [1.6] vs. 5.9 [2.0], p = 0.011). Patients experiencing wear-off reported being 'very satisfied' or 'somewhat satisfied' with their treatment less frequently than patients without wear-off (73.1 vs. 89.5%, respectively). Of patients reporting wear-off, 82.1% (n = 64) used supplemental medications during wear-off (non-steroidal anti-inflammatory drugs [68.8%, n = 44], muscle relaxants [42.2%, n = 27], and/or opioids [37.5%, n = 24]). CONCLUSIONS: In a predominantly female sample of bDMARD-treated patients with axSpA/AS and high disease activity, the majority expressed treatment satisfaction. However, most experienced wear-off between doses and relied on supplemental medications, including opioids, to manage symptoms.

Treatment Satisfaction and Decision-making from the Patient Perspective in Axial Spondyloarthritis: Real-World Data from a Descriptive Cross-sectional Survey Study from the ArthritisPower Registry.

OBJECTIVE: Aims were to 1) to characterize patient decision-making with treatment for axial spondyloarthritis (axSpA) and 2) to explore relationships among decision-making, treatment satisfaction, and biologic disease modifying antirheumatic drugs (bDMARDs). METHODS: ArthritisPower participants with physician-diagnosed axSpA were invited to complete an online survey about their treatment and their most recent physician visit. Analysis compared treatment decision by satisfaction and bDMARD status. RESULTS: Among the 274 participants, 87.2% were female, and the mean age was 50 years. Of participants, 79.5% had researched treatment before their most recent physician visit, and 56.9% discussed treatment change at their most recent physician visit. Of treatment-change discussions, 69.2% of them were related to escalation, compared with deescalation (27.6%) and/or switching (39.1%). Among those participants who discussed a change, 73.7% agreed to it because they felt that their disease was not being controlled (54.9%) or felt that it could be better controlled on new treatment (20.3%). Top symptoms prompting change were back/buttock pain (63.3%), other joint pain (55.1%), and fatigue (54.1%). Among bDMARD-treated participants (n = 128), important factors for treatment decisions were prevention of long-term axSpA consequences (92.9%) and doctor's advice (87.5%). Among 43.4% of participants reporting treatment dissatisfaction, 37% did not discuss treatment change. Current bDMARD use was more common in satisfied (61.9%) than dissatisfied participants (26.9%). CONCLUSION: In this cross-sectional study of a predominantly female axSpA population, patients frequently researched treatment options and discussed escalation with their providers. Under two-thirds of participants who were dissatisfied with treatment discussed changes at their most recent visit. Current bDMARD use was associated with higher satisfaction, and bDMARD users considered prevention of long-term consequences and doctor's advice to be very important for decision-making.

Serum Biomarkers for Prediction of Response to Methotrexate Monotherapy in Early Rheumatoid Arthritis: Results from the SWEFOT Trial.

OBJECTIVE: To investigate baseline levels of 12 serum biomarkers that constitute a multibiomarker disease activity test, as predictors of response to methotrexate (MTX) in patients with early rheumatoid arthritis (eRA). METHODS: In 298 patients from the Swedish Pharmacotherapy (SWEFOT) clinical trial, baseline serum levels of 12 proteins were analyzed for association with disease activity based on the 28-joint count Disease Activity Score (DAS28) after 3 months of MTX monotherapy using uni-/multivariate logistic regression. Primary outcome was low disease activity (LDA; DAS28 ≤ 3.2). RESULTS: Of 298 patients, 104 achieved LDA after 3 months on MTX. Four of the 12 biomarkers [C-reactive protein (CRP), leptin, tumor necrosis factor receptor I (TNF-RI), and vascular cell adhesion molecule 1 (VCAM-1)] significantly predicted LDA based on stepwise logistic regression analysis. Dichotomization of patients using receiver-operating characteristic curve analysis-based cutoffs for these biomarkers showed significantly higher proportions with LDA among patients with lower versus higher levels of CRP or leptin (40% vs 23%, p = 0.004, and 40% vs 25%, p = 0.011, respectively), as well as among those with higher versus lower levels of TNF-RI or VCAM-1 (43% vs 27%, p = 0.004, and 41% vs 25%, p = 0.004, respectively). Combined score based on these biomarkers, adjusted for known predictors of LDA (smoking, sex, and age), associated with decreased chance of LDA (adjusted OR 0.45, 95% CI 0.32-0.62). CONCLUSION: Low baseline levels of CRP and leptin, and high baseline levels of TNF-RI and VCAM-1 were associated with LDA after 3 months of MTX therapy in patients with eRA. Combination of these 4 biomarkers increased accuracy of prediction. [Trial registration number: NCT00764725].

A Multi-Biomarker Disease Activity Score and the Choice of Second-Line Therapy in Early Rheumatoid Arthritis After Methotrexate Failure.

OBJECTIVE: To investigate whether the Multi-Biomarker Disease Activity (MBDA) score predicts optimal add-on treatment in patients with early rheumatoid arthritis (RA) who were inadequate responders to MTX (MTX-IRs). METHODS: We analyzed data from 157 MTX-IRs (with a Disease Activity Score using the erythrocyte sedimentation rate [DAS28-ESR] >3.2) from the Swedish Pharmacotherapy (SWEFOT) trial who were randomized to receive triple therapy (MTX plus sulfasalazine plus hydroxychloroquine) versus MTX plus infliximab. The MBDA score as a predictor of the subsequent DAS28-based response to each second-line treatment was analyzed at randomization with the Breslow-Day test for 2 × 2 groups, using both validated categories (low [<30], moderate [30-44], and high [>44]) and dichotomized categories (lower [≤38] versus higher [>38]). RESULTS: Among the 157 patients, 12% had a low MBDA score, 32% moderate, and 56% high. Of those with a low MBDA score, 88% responded to subsequent triple therapy, and 18% responded to MTX plus infliximab (P = 0.006); for those with a high MBDA score, the response rates were 35% and 58%, respectively (P = 0.040). When using 38 as a cutoff for the MBDA score (29% patients with lower scores versus 71% with higher scores), the differential associations with response to triple therapy versus MTX plus infliximab were 79% versus 44% and 36% versus 58%, respectively (P = 0.001). Clinical and inflammatory markers had poorer predictive capacity for response to triple therapy or MTX plus infliximab. CONCLUSION: In patients with RA who had an inadequate response to MTX, the MBDA score categories were differentially associated with response to subsequent therapies. Thus, patients with post-MTX biochemical improvements (lower MBDA scores) were more likely to respond to triple therapy than to MTX plus infliximab. If confirmed, these results may help to improve treatment in RA.

Association of a multibiomarker disease activity score at multiple time-points with radiographic progression in rheumatoid arthritis: results from the SWEFOT trial.

OBJECTIVES: In rheumatoid arthritis (RA), predictive biomarkers for subsequent radiographic progression (RP) could improve therapeutic choices for individual patients. We previously showed that the multibiomarker disease activity (MBDA) score in patients with newly diagnosed RA identified patients at risk for RP. We evaluated the MBDA score at multiple time-points as a predictor of RP during 2 years of follow-up. METHODS: A subset of patients with RA (N=220) from the Swedish Farmacotherapy (SWEFOT) trial were analysed for MBDA score, disease activity score of 28 joints (DAS28), C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) at baseline (BL), month 3 and year 1, for predicting RP based on modified Sharp/van der Heijde scores at BL, year 1 and year 2. RESULTS: Patients with persistently low MBDA (<30) scores or those with a decrease from moderate (30-44) to low MBDA scores, did not develop RP during 2 years of follow-up. The highest risk for RP during 2 years of follow-up (42%) was observed among patients with persistently high (>44) MBDA scores. Among methotrexate non-responders with a high MBDA score at BL or month 3, significantly more of those who received triple therapy had RP at year 2 compared with those who received antitumour necrosis factor therapy. CONCLUSIONS: Measuring the MBDA score both before and during treatment in RA was useful for the assessment of individual patient risk for RP during 2 years of follow-up. In comparison with low CRP, ESR or DAS28, a low MBDA score at any time-point was associated with numerically lower proportions of RP. TRIAL REGISTRATION NUMBER: NCT00764725.