Analysis of patients with rheumatoid arthritis and higher radiographic progression: association of very high radiographic progression but not of intermediately high with worsening of patient-related outcomes.

OBJECTIVES: To analyse rheumatoid arthritis (RA)-patients depending on their individual peak radiographic progression. METHODS: We selected for the individual peak radiographic progression (Δ Ratingen scores/time) in patients of the Swiss registry SCQM. The baseline disease characteristics were compared using standard descriptive statistics. The change of DAS 28 (disease activity sore) and HAQ-DI (Health Assessment Questionnaire Disability Index) before and after peak progression was analysed with Wilcoxon signed rank tests. RESULTS: Of the 4,033 patients in the analysis, 3,049 patients had a peak radiographic progression rate between 0 and ≤10 in the Ratingen score per year, 773 between 10 and ≤20, 150 between 20 and ≤30, and 61 of >30 (defining groups A-D). Rheumatoid factor was more frequent in patient groups with a higher peak radiographic progression (71.1%, 79.2%, 85.3%, 88.5%, groups A-D). Peak radiographic progression at a rate >20/year (groups C-D) was not detected after December 2012. When the rate of radiographic progression before and after peak progression was analysed, it was significantly lower. The DAS 28 was significantly higher in all patient groups before peak progression and lower thereafter (p<0.001). Average HAQ-DI scores increased after peak radiographic progression in group D (p=0.005) whereas it was stable or even decreased among the patients of the other patient groups. CONCLUSIONS: These data show that the highest radiographic progression rates are rare and get less frequent over the last years. Higher disease activity precedes radiographic peak progression. Only the highest individual peak (change of Ratingen score >30/year) radiographic progression was followed by an increase of HAQ-DI scores.

Differential Changes in ACPA Fine Specificity and Gene Expression in a Randomized Trial of Abatacept and Adalimumab in Rheumatoid Arthritis.

INTRODUCTION: The biologics abatacept and adalimumab have different mechanisms of action (MoAs). We analyzed data from patients with rheumatoid arthritis treated in AMPLE (NCT00929864) to explore the pharmacodynamic effects of abatacept or adalimumab on anti-citrullinated protein antibodies (ACPAs) and gene expression. METHODS: AMPLE was a phase IIIb, 2-year, randomized, head-to-head trial of abatacept versus adalimumab. Post hoc analyses of baseline anti-cyclic citrullinated peptide-2 (anti-CCP2, an ACPA surrogate) positive (+) status and ACPA fine-specificity profiles over time, as well as transcriptional profiling (peripheral whole blood), were performed. RESULTS: Of 646 patients treated (abatacept, n = 318; adalimumab, n = 328), ACPA and gene expression data were available from 508 and 566 patients, respectively. In anti-CCP2+ patients (n = 388), baseline fine specificities for most ACPAs were highly correlated; over 2 years, levels decreased with abatacept but not adalimumab. By year 2, expression of genes associated with T cell co-stimulation and antibody production was lower for abatacept versus adalimumab; expression of genes associated with proinflammatory signaling was lower for adalimumab versus abatacept. Treatment modulated the expression of T- and B-cell gene signatures, with differences in CD8+ T cells, activated T cells, plasma cells, B cells, natural killer cells (all lower with abatacept versus adalimumab), and polymorphonuclear leukocytes (higher with abatacept versus adalimumab). CONCLUSIONS: In AMPLE, despite similar clinical outcomes, data showed that pharmacodynamic/genetic changes after 2 years of abatacept or adalimumab were consistent with drug MoAs. Further assessment of the relationship between such changes and clinical outcomes, including prediction of response, is warranted. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT00929864.

Background Glucocorticoid Therapy Has No Impact on Efficacy and Safety of Abatacept or Adalimumab in Patients with Rheumatoid Arthritis.

To date, the impact of background glucocorticoids (GC) on the efficacy and safety of abatacept or adalimumab in patients with active rheumatoid arthritis (RA) is not clearly established. This post hoc analysis of (AMPLE) trial (NCT00929864) compared efficacy and safety outcomes over 2 years in patients treated with abatacept or adalimumab plus background methotrexate (MTX), who continued GC (≤10 mg/day) versus those who were not receiving GC (no-GC). Of 646 randomized patients, 317 received abatacept + MTX (161 GC, 156 no-GC) and 326 received adalimumab + MTX (162 GC, 164 no-GC). At Year 2, the adjusted mean changes from baseline in Disease Activity Score (DAS28 C-reactive protein (CRP)) and Health Assessment Questionnaire-Disability Index (HAQ-DI) were not significantly different in the GC versus no-GC subgroups receiving abatacept or adalimumab. A similar proportion of patients achieved remission, HAQ-DI score improvement ≥0.3 and radiographic progression rates. No clinically meaningful safety differences were observed between GC versus no-GC subgroups either with abatacept or adalimumab. In patients with active RA of similar baseline disease activity treated with abatacept or adalimumab plus background MTX, there was no additional value of background GC on clinical, functional or radiographic outcomes over two years.

Correction to: Upadacitinib improves patient-reported outcomes in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying antirheumatic drugs: results from SELECT-NEXT.

An amendment to this paper has been published and can be accessed via the original article.

A multicenter, open-label study to evaluate the safe and effective use of a new electromechanical auto-injection device for self-injection of certolizumab pegol.

BACKGROUND: ava® is a new reusable electromechanical auto-injector (e-Device) with disposable, single-use certolizumab pegol (CZP) dispensing cartridges. METHODS: RA0098 (NCT03357471) was a US, multicenter, open-label, phase 3 study designed to assess whether the e-Device can be used safely and effectively by self-injecting patients. CZP pre-filled syringe (PFS) self-injecting patients (≥18 years) diagnosed with rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis, plaque psoriasis, and Crohn's disease received training and self-injected CZP using the e-Device at 2 visits. The primary outcome was the proportion of patients able to self-inject safely and effectively at Visit 2, defined as: 1) complete dose delivery, and 2) no adverse events related to the e-Device precluding its continued use. RESULTS: 65/67 patients (97.0%) completed the study, 64/65 (98.5%) performed safe and effective self-injection at Visit 2, and 67/67 (100%) performed safe and effective self-injection at Visit 1. Patient satisfaction and self-confidence increased over the two visits. Overall, patients reported a preference for the e-Device (58/65; 89.2%) compared to a PFS (4/65; 6.2%). CONCLUSIONS: Patients were able to safely and effectively self-inject CZP using the e-Device and most preferred ava® over a PFS. No safety-related findings impacting the benefit-risk ratio of CZP were identified.

Efficacy and Safety of Long-Term Baricitinib With and Without Methotrexate for the Treatment of Rheumatoid Arthritis: Experience With Baricitinib Monotherapy Continuation or After Switching From Methotrexate Monotherapy or Baricitinib Plus Methotrexate.

OBJECTIVE: To evaluate the long-term efficacy and safety of maintaining baricitinib monotherapy in patients with active rheumatoid arthritis (RA) originally treated with baricitinib monotherapy or switched from methotrexate (MTX) or the combination of baricitinib plus MTX to baricitinib monotherapy. METHODS: This is a post hoc analysis of patients from the RA-BEGIN study who entered a long-term extension, RA-BEYOND, and were assessed for up to 24 weeks. In RA-BEGIN, MTX-naive patients with early active RA were randomized to MTX monotherapy, baricitinib 4 mg monotherapy, or baricitinib 4 mg plus MTX. At week 52, all patients entering RA-BEYOND received baricitinib 4 mg monotherapy. MTX could be prescribed during RA-BEYOND at the investigator's discretion. RESULTS: Patients in RA-BEYOND who were not rescued in RA-BEGIN (n = 423) were evaluated. Of these, 47% continued baricitinib monotherapy and 53% added MTX, with similar proportions from the 3 original arms. Patients with lower disease activity at the RA-BEYOND baseline generally continued to do well with baricitinib monotherapy as assessed by the Simplified Disease Activity Index, the Clinical Disease Activity Index, and the Health Assessment Questionnaire disability index scores. Patients prescribed MTX had higher disease activity at the RA-BEYOND baseline and had improved disease activity after the addition of MTX. Safety outcomes were similar across treatment groups. CONCLUSION: Many patients responded well to continued baricitinib monotherapy or to switching to baricitinib monotherapy from MTX monotherapy or baricitinib plus MTX, showing sustained or improved disease control. The groups of patients who had less disease control on their original therapies showed sustained or improved disease control with the addition of MTX to baricitinib.

Combination Treatment with Antibiotics and Glucocorticosteroids for Severe Ischemic Colitis.

BACKGROUND/AIMS: Ischemic colitis (IC) is most common in the elderly and patients with multiple comorbidities. It carries significant mortality. As yet no evidence-based therapeutic management exists. Aim of the study was to test therapeutic efficacy of a combination of prednisolone and antibiotics. METHODS: Prospective cohort study with retrospective analysis performed in a single teaching hospital in Germany. Consecutive patients with strict diagnostic criteria of severe IC, including colonoscopy, histology, and laboratory tests, were recruited. Main outcome measures were in-hospital mortality and number of operations counted within the hospital stay. Severity scores were calculated and biomarkers determined during the course of the hospital stay. RESULTS: A total of 342 patients with an International Classification of Diseases of IC were identified. About 151 patients met the diagnostic criteria and a total of 44 patients fulfilled all inclusion and exclusion criteria of severe IC and constituted the group of patients eligible for analysis. Five out of 44 patients (11.4%) died (in-hospital mortality). Surgery was performed in 3 patients (6.8%), 2 patients survived. The hospital stay lasted 14.0 ± 8.5 day and was significantly correlated with comorbidity (rs = 0.314, p = 0.038). No serious adverse events were observed. CONCLUSION: This is the first prospective study on therapeutic efficacy and safety in severe IC. The combination of intravenous antibiotics and intravenous prednisolone turned out to be safe and revealed promising efficacy.

Upadacitinib improves patient-reported outcomes in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying antirheumatic drugs: results from SELECT-NEXT.

BACKGROUND: To evaluate the effect of upadacitinib on patient-reported outcomes (PROs) in patients with RA who had an inadequate response to csDMARDs. METHODS: Patients in SELECT-NEXT, a randomised controlled trial, were on a background of csDMARDs and received upadacitinib 15 mg and 30 mg or placebo daily for 12 weeks. PROs included Patient Global Assessment of Disease Activity (PtGA), pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), duration and severity of morning (AM) joint stiffness, Short Form 36 Health Survey (SF-36), and Work Instability Scale for RA (RA-WIS). Least squares mean (LSM) changes were based on mixed-effect repeated measure models. Percentages of patients reporting improvements ≥ minimum clinically important differences (MCIDs) and scores ≥ normative values and number needed to treat (NNT) were determined; group comparisons used chi-square tests. RESULTS: Data from 661 patients were analysed. Compared with placebo, patients receiving upadacitinib reported statistically significant improvements (both doses, P < 0.05) in PtGA, pain, HAQ-DI, FACIT-F, duration and severity of AM stiffness, SF-36 (PCS and 6/8 domains), and RA-WIS at week 12. Significantly, more upadacitinib-treated patients (both doses, P < 0.05) reported improvements ≥ MCID in PtGA, pain, HAQ-DI, FACIT-F, AM stiffness, SF-36 (PCS and 4 or 7/8 domains), and RA-WIS and scores ≥ normative values in HAQ-DI, FACIT-F, and SF-36 (PCS and 4 or 5/8 domains). For most PROs, the incremental NNT with upadacitinib to report clinically meaningful improvement from baseline ranged from 4 to 8 patients. CONCLUSIONS: Upadacitinib 15 mg or 30 mg daily for 12 weeks resulted in significant and clinically meaningful improvements in global disease activity, pain, physical function, fatigue, duration and severity of AM stiffness, HRQOL, and work instability among csDMARD-IR patients with RA. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02675426. Retrospectively registered 5 February 2016.

Effects of upadacitinib on patient-reported outcomes: results from SELECT-BEYOND, a phase 3 randomized trial in patients with rheumatoid arthritis and inadequate responses to biologic disease-modifying antirheumatic drugs.

BACKGROUND: Patient-reported outcomes (PROs) are important when evaluating treatment benefits in rheumatoid arthritis (RA). We compared upadacitinib, an oral, selective JAK-1 inhibitor, with placebo to assess clinically meaningful improvements in PROs in patients with RA who have had inadequate responses to biologic disease-modifying antirheumatic drugs (bDMARD-IR). METHODS: PRO responses between upadacitinib 15 mg or 30 mg and placebo were evaluated at week 12 from the SELECT-BEYOND trial. Improvement was determined by measuring Patient Global Assessment of Disease Activity (PtGA), pain, Health Assessment Questionnaire Disability Index (HAQ-DI), Short Form-36 Health Survey (SF-36), duration and severity of morning (AM) stiffness, and Insomnia Severity Index (ISI). Least squares mean changes and percentage of patients reporting improvements ≥ minimum clinically important differences (MCID) and scores greater than or equal to normative values were determined. The number needed to treat (NNT) to achieve clinically meaningful improvements was calculated. RESULTS: In 498 patients, both upadacitinib doses resulted in statistically significant changes from baseline versus placebo in PtGA, pain, HAQ-DI, SF-36 Physical Component Summary (PCS), 7 of 8 SF-36 domains (15 mg), 6 of 8 SF-36 domains (30 mg), and AM stiffness duration and severity. Compared with placebo, more upadacitinib-treated patients reported improvements ≥ MCID in PtGA, pain, HAQ-DI, SF-36 PCS, 7 of 8 SF-36 domains (15 mg), 5 of 8 SF-36 domains (30 mg), AM stiffness duration and severity, and ISI (30 mg) and scores ≥ normative values in HAQ-DI and SF-36 domains. Across most PROs, NNTs to achieve MCID with upadacitinib ranged from 4 to 7 patients. CONCLUSIONS: In bDMARD-IR RA patients, upadacitinib (15 mg or 30 mg) improved multiple aspects of quality of life, and more patients reached clinically meaningful improvements approaching normative values compared with placebo. TRIAL REGISTRATION: The trial is registered with ClinicalTrials.gov (NCT02706847), registered 6 March 2016.

Efficacy of Abatacept and Adalimumab in Patients with Early Rheumatoid Arthritis With Multiple Poor Prognostic Factors: Post Hoc Analysis of a Randomized Controlled Clinical Trial (AMPLE).

INTRODUCTION: Patients with rheumatoid arthritis (RA) with poor prognostic factors, such as seropositivity for anti-citrullinated protein antibodies and early erosions, may benefit from early intensive treatment. However, information to guide physicians on the best choice of therapy in these patients is limited. The objective of this study was to describe the efficacy of subcutaneous abatacept versus adalimumab over 2 years in patients with seropositive, erosive early RA in the AMPLE study. METHODS: This exploratory post hoc analysis compared clinical, functional and radiographic outcomes in two subsets of patients: patients with early RA (≤ 6 months' disease duration) who were seropositive for rheumatoid factor and/or anti-citrullinated protein antibodies and had > 1 radiographic erosion (Cohort 1); and patients with RA and absence of ≥ 1 of these inclusion criteria (Cohort    2). RESULTS: Of the 646 randomized patients, Cohort 1 included 38 patients receiving abatacept and 45 receiving adalimumab, and Cohort 2 included 280 patients receiving abatacept and 283 receiving adalimumab. Baseline demographics and disease characteristics were generally similar between treatment groups in both cohorts. Over 2 years, in Cohort 1, the adjusted mean change from baseline in the Disease Activity Score in 28 joints (using C-reactive protein) was numerically greater for abatacept than for adalimumab (mean difference at day 365 was 0.9, 95% confidence interval - 1.47 to - 0.33). Similar patterns of improvement were observed for other disease activity measures and physical function, but not for radiographic outcomes. No treatment-related differences were observed in Cohort 2. CONCLUSION: This analysis indicates a trend towards improved disease activity and physical function with abatacept versus adalimumab in patients with seropositive, erosive early RA. TRIAL REGISTRATION: ClinicalTrials.gov NCT00929864. FUNDING: Bristol-Myers Squibb.

From drug-delivery device to disease management tool: a study of preferences for enhanced features in next-generation self-injection devices.

PURPOSE: To quantify rheumatology patient preferences and willingness to pay (WTP) for features differentiating enhanced from standard self-injection devices and to investigate differences among subgroups. PATIENTS AND METHODS: Patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) were recruited in the UK. A discrete-choice experiment was used to elicit preferences; respondents were presented with 10 choices between 3 different devices: a free standard disposable device, and 2 hypothetical reusable devices characterized by presence/absence of skin sensor, injection speed control, on-screen instructions, injection reminders, electronic log, and large grip. Every hypothetical device included a cost component to assess WTP for each enhanced feature. A random-parameters logit model was used to estimate preference weights and WTP. RESULTS: Data were collected from 323 respondents by electronic survey (15/11/2017-15/02/2018; RA: 108; PsA: 103; axSpA: 112). On average, the skin sensor was the most preferred feature (£30), followed by injection speed control, injection reminders, electronic log (~£20 each), on-screen instructions (~£12), and a device with a small, rather than large grip (~£7). Similar preferences for attributes were observed across condition subgroups except for grip size: axSpA patients preferred small grip (~£27); PsA patients preferred large grip (~£19). Overall, respondents preferred reusable devices with all enhanced features (WTP value: £85) over the standard device. RA patients exhibited a higher WTP (£145) than PsA (£102) or axSpA (£62) for the same enhanced device. CONCLUSION: Patients positively valued reusable self-injection devices with enhanced features, which may improve patient experience, potentially improving treatment adherence, clinical, and economic outcomes.

Low rates of radiographic progression of structural joint damage over 2 years of baricitinib treatment in patients with rheumatoid arthritis.

Objectives: To evaluate radiographic progression of structural joint damage over 2 years in patients with rheumatoid arthritis from baricitinib clinical trials who were disease-modifying antirheumatic drug (DMARD)-naïve or had an inadequate response to conventional synthetic DMARDs (csDMARD-IR). Methods: Patients had completed one of three phase III studies and entered a long-term extension (LTE) study, continuing on the same baricitinib dose as at originating study completion. At 52 weeks, DMARD-naïve patients receiving methotrexate (MTX) or combination therapy (baricitinib 4 mg+MTX) were switched to baricitinib 4 mg monotherapy (±MTX per investigator opinion); MTX-IR patients receiving adalimumab were switched to baricitinib 4 mg on background MTX. At 24 weeks, csDMARD-IR patients receiving placebo were switched to baricitinib 4 mg on background csDMARD. Radiographs at baseline, year 1 and year 2 were scored using the van der Heijde modified Total Sharp Score. Linear extrapolation was used for missing data. Results: Of 2573 randomised patients, 2125 (82.6%) entered the LTE, of whom 1893 (89.1%) entered this analysis. At year 2, progression was significantly lower with initial baricitinib (monotherapy or combination therapy) versus initial MTX in DMARD-naïve patients (proportion with non-progression defined by ≤smallest detectable change (SDC): 87.3% baricitinib 4 mg+MTX; 70.6% MTX; p≤ 0.001). In MTX-IR patients, progression with initial baricitinib was significantly lower than with initial placebo and similar to initial adalimumab (≤SDC: 82.7% baricitinib 4 mg; 83.5% adalimumab; 70.6% placebo; p≤0.001). In csDMARD-IR patients, significant benefit was seen with baricitinib 4 mg (≤SDC: 87.2% vs 73.2% placebo; p≤0.01). Conclusions: Treatment with once-daily baricitinib resulted in low rates of radiographic progression for up to 2 years.

Can switching to abatacept therapy in patients with rheumatoid arthritis on background methotrexate reverse TNF-inhibitor-induced antinuclear autoantibody/double-stranded DNA autoantibody conversion? An analysis of the AMPLE and ATTEST trials.

OBJECTIVES: To explore antinuclear autoantibody (ANA) and anti-double-stranded DNA (anti-dsDNA) autoantibody development during abatacept and tumour necrosis factor inhibitor (TNFi) treatment, and effects of switching from TNFi to abatacept in ANA/anti-dsDNA autoantibody-positive patients. METHODS: This was a post hoc analysis of biologic-naïve patients with active RA in ATTEST and AMPLE. In AMPLE, patients received subcutaneous abatacept or adalimumab (2 years). In ATTEST, patients received intravenous abatacept or infliximab (1 year), or placebo (6 months) then abatacept (6 months); at 1 year, all patients could receive abatacept (open-label long-term extension). Serum ANA/anti-dsDNA autoantibody levels were measured at baseline, Month 6 (ATTEST only), Years 1 and 2. RESULTS: At baseline, 25.7 and 0.9% (AMPLE), and 21.6 and 8.4% of patients (ATTEST) were ANA/anti-dsDNA autoantibody positive, respectively. More baseline ANA/anti-dsDNA autoantibody-negative patients became positive during TNFi than abatacept treatment. In ATTEST (TNFi group), 48.5% (48/99; ANA) and 48.3% (57/118; anti-dsDNA) of patients seroconverted to positive status by Year 1, falling to 22.4% (22/98 ANA) and 13.3% (15/113; anti-dsDNA) by Year 2 after switching to abatacept. Of ANA/anti-dsDNA autoantibody-positive patients at Year 1, 41.9% and 68.9%, were negative at Year 2. CONCLUSIONS: ANA/anti-dsDNA seroconversion was more frequent with TNFi than abatacept therapy; TNFi-associated seroconversion decreased after switching from TNFi to abatacept.

A Targeted Literature Review Examining Biologic Therapy Compliance and Persistence in Chronic Inflammatory Diseases to Identify the Associated Unmet Needs, Driving Factors, and Consequences.

Chronic inflammatory diseases (CIDs) represent a substantial clinical and economic burden to patients, providers, payers and society overall. Biologics, such as tumor necrosis factor inhibitors (TNFi), have emerged as effective treatment options for patients with CIDs. However, the therapeutic potential of biologics is not always achieved in clinical practice, with results from studies examining the use of biologics in real-world settings suggesting lower levels of treatment effectiveness compared with clinical trial results. Using a targeted approach, this literature review demonstrates that compliance and persistence with biologic therapy is suboptimal and that this has implications for both clinical outcomes and treatment costs. The review identified a variety of predictors of treatment compliance and persistence, including increased age, female gender, presence of comorbidities, increased disease activity, longer disease duration, smoking, increased body mass index, higher biologic treatment dose, higher treatment cost and lower health-related quality-of-life scores. Patients often cited factors associated with medication delivery as a reason for non-compliance and non-persistence, and device-related improvements to treatment delivery were associated with higher rates of compliance and persistence. The articles identified in this review provide insights that have the potential to help guide the development of new solutions to improve disease management and optimize treatment regimens. This has the potential to benefit patients' health by improving clinical outcomes and to reduce the burden to society by limiting the economic impact of patients' disease. FUNDING: UCB Pharma.

Clinical and radiographic course of early undifferentiated arthritis under treatment is not dependent on the number of joints with erosions at diagnosis: results from the Swiss prospective observational cohort.

OBJECTIVE: To analyse whether early arthritis patients who do not fulfil the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 classification criteria for rheumatoid arthritis (RA) have a different course of the disease dependent on whether they can or cannot be classified as RA because of radiographic disease (EULAR task force) at diagnosis. METHODS: For this observational study within the Swiss RA cohort SCQM, we included patients with early undifferentiated arthritis (disease duration ≤1 year), who had not received any previous disease-modifying antirheumatic drugs (DMARDs). 2010 ACR/EULAR criteria negative patients were separated into two groups (radiographic vs non-radiographic arthritis) depending on whether or not they had radiographic changes defined as erosive disease by a EULAR task force (≥3 joints with erosions). The primary outcome measure was the radiographic progression detected employing the Ratingen erosion score. Health Assessment Questionnaire (HAQ) and DAS-28 were used as secondary outcome measures. The average observation period was 4 years. RESULTS: A total of 592 patients were analysed. 240 were not classifiable as RA by application of the 2010 ACR/EULAR criteria at baseline. In 57 patients, radiographs at the first visit were not available. 133 patients had radiographic arthritis and 50 non-radiographic arthritis. Treatment was initiated in all patients with DMARDs, mostly methotrexate. No differences in DAS-28 and HAQ scores were found during follow-up. The average erosion scores were higher among patients with initially radiographic arthritis throughout the study. The progression of erosion scores over time, however, was higher in patients with initially non-radiographic arthritis with less subsequent radiological progression (3.3 erosions/year vs 0.4, respectively, p<0.0001). CONCLUSIONS: The clinical and radiographic course of early undifferentiated arthritis under treatment was not dependent on the presence of erosions in three or more joints (ie, the definition of radiographic disease by the EULAR task force) at diagnosis in our cohort.

Long-Term Increase of Radiographic Damage and Disability in Patients with RA in Relation to Disease Duration in the Era of Biologics. Results from the SCQM Cohort.

OBJECTIVES: There is little information on the relation between disease duration, disability and radiographic outcome since the introduction of biologics into the therapy of rheumatoid arthritis (RA). No long -term cohort studies have been conducted on this subject so far. To analyse radiographic damage, disability, and disease activity in RA-patients dependent on disease duration in the Swiss national RA cohort (SCQM). METHODS: The primary outcome was the association between the radiographic destruction, assessed by Ratingen scores, and disease duration. All patients with at least one clinical visit were analysed with polynomial and multiple negative binomial models. RESULTS: The disease duration in the 8678 patients with available radiographs analysed ranged between less than 1 and more than 65 years (median 8.3). Disease duration and radiographic destruction were significantly associated with an average increase of Ratingen scores by 8.3% per year. Apart from disease duration, positive rheumatoid factor was the strongest predictor for radiographic destruction. While DAS28-scores remained stable in patients with a disease duration of more than 5 years (median DAS28 2.8), HAQ-DI scores increased continuously by 0.018 for each additional year. CONCLUSION: In this RA cohort, patients show a continuous increase of articular destruction and physical disability in parallel with disease duration. Even when nowadays a satisfactory control of disease activity can be achieved in most patients, RA remains a destructive disease leading to joint destruction and physical disability in many patients.

Response to baricitinib therapy in patients with rheumatoid arthritis with inadequate response to csDMARDs as a function of baseline characteristics.

OBJECTIVE: We analysed the effects of baseline characteristics on the safety and efficacy of baricitinib in patients with rheumatoid arthritis (RA) with inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) from two phase III trials. METHODS: In RA-BEAM (NCT01710358), patients with inadequate response to methotrexate were randomised to placebo, baricitinib 4 mg or adalimumab 40 mg. RA-BUILD (NCT01721057) patients had inadequate response to ≥1 csDMARDs and were randomised to either placebo or once-daily baricitinib (2 or 4 mg). Both study populations were naïve to biologic DMARDs (bDMARDs). Primary end point for both studies was American College of Rheumatology 20% improvement (ACR20) response at week 12. Pooled data from the two trials were analysed post hoc based on select subgroups defined by age, previous csDMARD use, baseline RA disease activity, etc, with assessment of clinical and safety outcomes at week 12 and radiographic outcomes at week 24 for the baricitinib 4 mg and placebo-treated patients. RESULTS: Efficacy was observed with baricitinib 4 mg treatment irrespective of patient demographics and baseline disease characteristics. ORs primarily favoured baricitinib over placebo in the ACR20 response. In other outcomes such as Disease Activity Score for 28 joints based on high-sensitivity C reactive protein levels, Simplified Disease Activity Index score ≤11 and radiographic progression, baricitinib 4 mg showed better responses than placebo regardless of baseline characteristics. Safety events were more common in patients over 65 years, but similar between baricitinib 4 mg and placebo patients. CONCLUSION: Baseline characteristics did not substantially affect clinical response to baricitinib 4 mg in patients with RA with inadequate response to csDMARDs.

Efficacy and safety of monotherapy with sirukumab compared with adalimumab monotherapy in biologic-naïve patients with active rheumatoid arthritis (SIRROUND-H): a randomised, double-blind, parallel-group, multinational, 52-week, phase 3 study.

OBJECTIVE: This randomised, double-blind, parallel-group, phase 3 study compared monotherapy with sirukumab, an anti-interleukin-6 cytokine monoclonal antibody, with adalimumab monotherapy in patients with rheumatoid arthritis (RA). METHODS: Biologic-naïve patients with active RA who were inadequate responders or were intolerant to, or inappropriate for, methotrexate were randomised to subcutaneous sirukumab 100 mg every 2 weeks (n=187), sirukumab 50 mg every 4 weeks (n=186) or adalimumab 40 mg every 2 weeks (n=186). Primary endpoints at week 24 were change from baseline in Disease Activity Score in 28 joints (DAS28) using erythrocyte sedimentation rate (ESR) and proportion of patients achieving an American College of Rheumatology (ACR) 50 response; these endpoints were tested in sequential order. This study is registered at EudraCT (number: 2013-001417-32) and ClinicalTrials.gov (number: NCT02019472). RESULTS: Significantly greater improvements from baseline in mean (SD) DAS28 (ESR) were observed at week 24 with sirukumab 100 mg every 2 weeks (-2.96 (1.580)) versus adalimumab 40 mg every 2 weeks (-2.19 (1.437); P<0.001). Sirukumab 50 mg every 4 weeks also showed significantly greater improvement from baseline at week 24 in DAS28 (ESR) (-2.58 (1.524)) compared with adalimumab (P=0.013). The ACR50 response rates with the 100 mg (35.3%) and 50 mg (26.9%) doses of sirukumab were comparable to that with adalimumab (31.7%) at week 24. The safety profile of sirukumab was consistent with that observed with anti-interleukin-6 receptor antibodies. A dose-related effect on the incidence of injection-site reactions was observed with sirukumab. CONCLUSION: Sirukumab monotherapy showed greater improvements in DAS28 (ESR), but similar ACR50 response rates, versus adalimumab monotherapy.

Patient-reported outcomes of baricitinib in patients with rheumatoid arthritis and no or limited prior disease-modifying antirheumatic drug treatment.

BACKGROUND: This study evaluates patient-reported outcomes (PROs) in a double-blind, phase III study of baricitinib as monotherapy or combined with methotrexate (MTX) in patients with active rheumatoid arthritis (RA) with no or minimal prior conventional synthetic disease-modifying antirheumatic drugs (DMARDs) and naïve to biological DMARDs. METHODS: Patients were randomized 4:3:4 to MTX administered once weekly (N = 210), baricitinib monotherapy (4 mg once daily (QD), N = 159), or combination of baricitinib (4 mg QD) and MTX (baricitinib + MTX, N = 215). PROs included the Patient's Global Assessment of Disease Activity (PtGA), patient's assessment of pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), duration of morning joint stiffness (MJS), worst joint pain, worst tiredness, Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA), Short Form 36 version 2, Acute (SF-36); and EuroQol 5-Dimensions (EQ-5D) Health State Profile. Comparisons were assessed with analysis of covariance (ANCOVA) and logistic regression models. RESULTS: Compared to MTX, patients in both baricitinib groups reported greater improvement (p ≤ 0.01) in HAQ-DI, PtGA, pain, fatigue, worst join pain, SF-36 physical component score, and EQ-5D at weeks 24 and 52. For the SF-36 mental component score, patients in both baricitinib groups reported statistically significant improvements (p ≤ 0.01) at week 52 compared to MTX-treated patients. Statistically significant improvements (p ≤ 0.05) were observed with the WPAI-RA for the baricitinib groups vs. MTX at week 24 and for the WPAI-RA daily activity and work productivity measures for baricitinib + MTX at week 52. CONCLUSIONS: In this study, baricitinib alone or in combination with MTX, when used as initial therapy, resulted in significant improvement compared to MTX in the majority of the pre-specified PRO measures. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01711359 . Registered on 18 October 2012.

Chronic Disease and Self-Injection: Ethnographic Investigations into the Patient Experience During Treatment.

INTRODUCTION: Drug administration by self-injection provides an option to treat chronic inflammatory diseases such as rheumatoid arthritis (RA) and Crohn's disease (CD). However, a negative self-injection experience for patients may reduce patient adherence to the recommended treatment regimen. In this study, a holistic approach was used to identify common themes along the treatment pathway and at self-injection that, if changed, could improve patient experience and treatment outcomes. METHODS: Two ethnographic studies were conducted: Field Insights CODE (FI[CODE]) examined the treatment pathway within the context of the experience of living with RA or CD, and Injection Mission 2020 (IM2020) focused on the moment of self-injection. FI(CODE) used an open ethnographic approach to interview 62 patients and 10 healthcare professionals (HCPs) from the US and UK. IM2020 included a review of over 50 injection device design information sources from the sponsor, and interviews with 9 patients, 8 HCPs, and 5 medical device designers from the US, UK, Canada, and Japan. RESULTS: FI(CODE) identified suboptimal treatment practices along the treatment pathway in four key areas: treatment team communication, treatment choice, patient empowerment, and treatment delivery. Patients with more treatment options and greater disease understanding were less likely to struggle with the treatment process. IM2020 demonstrated that five related components influenced the self-injection experience: delivery process, emotional state, social perception, educational level, and ritualization of the self-injection process. CONCLUSION: These analyses highlight several potential areas for improvement, including aligning the device more to patients' needs to improve treatment adherence, better accessibility to educational resources to increase patient disease understanding, and guidance to empower patients to develop an optimal personalized self-injection ritual. FUNDING: UCB Pharma.

Some medicines used to treat long-term conditions, such as rheumatoid arthritis or Crohn's disease, are injected under the skin. Often, patients can choose to inject medicines themselves (self-injection). This must be done correctly for the medicines to work properly. But, the training surrounding self-injection is uneven and often cannot address the fundamental problems facing all self-injecting patients.What healthcare improvements could help patients self-inject successfully? To find out, we interviewed people living with rheumatoid arthritis or Crohn's disease, while others were doctors, nurses, and people who design injection devices.We found four common problems in the overall healthcare that patients received:1.There were communication problems between different healthcare professionals and between healthcare professionals and patients, for example about treatment options or goals.2.Each level in the healthcare system (e.g., the nurse, doctor, hospital board, health insurance company) made decisions that limited how many treatment options were presented to patients for consideration.3.Patients were not empowered, as they felt they lacked personal input, information, and control in treatment decisions.4.Healthcare professionals focused on disease treatment but not patient experience; they did not fully explain how to perform injections (delivery), leaving patients to figure it out by trial and error. In addition, five factors were identified that affected patients' experiences of self-injection:1.Process of injection: minimal one-on-one instruction for self-injection left some patients anxious and more prone to mistakes.2.Emotions: some patients were better than others at 'overriding' emotions (e.g., fear) when self-injecting.3.Views on injections: there was negative social stigma around injections, but patients had greater trust in more technological, modern devices.4.Education: doctors often failed to explain how to manage fear and anxiety.5.Developing a ritual: patients with a ritualized routine for when, where, and how to self-inject were more confident. If doctors and nurses can support patients by providing a greater choice of treatments and injection devices, and teaching more about self-injection, this could improve patients' experiences and allow medications to work better. Healthcare professionals should help patients to develop their own, optimal routine for self-injection.