There is a need for effective and safe treatment during pregnancy in women with chronic inflammatory diseases. This study evaluated placental transfer of certolizumab pegol (CZP), an Fc-free ...anti-tumour necrosis factor drug, from CZP-treated pregnant women to their infants.
CRIB was a pharmacokinetic (PK) study of women ≥30 weeks pregnant receiving commercial CZP for a locally approved indication (last dose ≤35 days prior to delivery). Blood samples were collected from mothers, umbilical cords and infants at delivery, and infants again at weeks 4 and 8 post-delivery. CZP plasma concentrations were measured with a highly sensitive and CZP-specific electrochemiluminescence immunoassay (lower limit of quantification 0.032 μg/mL).
Sixteen women entered and completed the study. Maternal CZP plasma levels at delivery were within the expected therapeutic range (median range 24.4 5.0-49.4 μg/mL). Of the 16 infants, 2 were excluded from the per-protocol set: 1 due to missing data at birth and 1 due to implausible PK data. Of the remaining 14 infants, 13 had no quantifiable CZP levels at birth (<0.032 μg/mL), and 1 had a minimal CZP level of 0.042 μg/mL (infant/mother plasma ratio 0.0009); no infants had quantifiable CZP levels at weeks 4 and 8. Of 16 umbilical cord samples, 1 was excluded due to missing data; 3/15 had quantifiable CZP levels (maximum 0.048 μg/mL).
There was no to minimal placental transfer of CZP from mothers to infants, suggesting lack of
foetal exposure during the third trimester. These results support continuation of CZP treatment during pregnancy, when considered necessary.
NCT02019602; Results.
To update and integrate the recommendations for ankylosing spondylitis and the recommendations for the use of tumour necrosis factor inhibitors (TNFi) in axial spondyloarthritis (axSpA) into one set ...applicable to the full spectrum of patients with axSpA. Following the latest version of the European League Against Rheumatism (EULAR) Standardised Operating Procedures, two systematic literature reviews first collected the evidence regarding all treatment options (pharmacological and non-pharmacological) that were published since 2009. After a discussion of the results in the steering group and presentation to the task force, overarching principles and recommendations were formulated, and consensus was obtained by informal voting. A total of 5 overarching principles and 13 recommendations were agreed on. The first three recommendations deal with personalised medicine including treatment target and monitoring. Recommendation 4 covers non-pharmacological management. Recommendation 5 describes the central role of non-steroidal anti-inflammatory drugs (NSAIDs) as first-choice drug treatment. Recommendations 6-8 define the rather modest role of analgesics, and disprove glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) for axSpA patents with predominant axial involvement. Recommendation 9 refers to biological DMARDs (bDMARDs) including TNFi and IL-17 inhibitors (IL-17i) for patients with high disease activity despite the use (or intolerance/contraindication) of at least two NSAIDs. In addition, they should either have an elevated C reactive protein and/or definite inflammation on MRI and/or radiographic evidence of sacroiliitis. Current practice is to start with a TNFi. Switching to another TNFi or an IL-17i is recommended in case TNFi fails (recommendation 10). Tapering, but not stopping a bDMARD, can be considered in patients in sustained remission (recommendation 11). The final two recommendations (12, 13) deal with surgery and spinal fractures. The 2016 Assessment of SpondyloArthritis international Society-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA.
To estimate sacroiliac joint radiographic (X-SIJ) progression in patients with axial spondyloarthritis (axSpA) and to evaluate the effects of inflammation on MRI (MRI-SIJ) on X-SIJ progression.
X-SIJ ...and MRI-SIJ at baseline and after 2 and 5 years in patients with recent onset axSpA from the DESIR cohort were scored by three central readers. Progression was defined as (1) the shift from non-radiographic (nr) to radiographic (r) sacroiliitis (by modified New York (mNY) criteria) or alternative criteria, (2) a change of at least one grade or (3) a change of at least one grade but ignoring a change from grade 0 to 1. The effects of baseline inflammation on MRI-SIJ on 5-year X-SIJ damage (mNY) were tested by generalised estimating equations.
In 416 patients with pairs of baseline and 5-year X-SIJ present, net progression occurred in 5.1% (1), 13.0% (2) and 10.3% (3) respectively, regarding a shift from nr-axSpA to r-axSpA (1), a change of at least one grade (2) or a change of at least one grade but ignoring a change from grade 0 to 1 (3). Baseline MRI-SIJ predicted structural damage after 5 years in human leukocyte antigen-B27 (HLA-B27) positive (OR 5.39 (95% CI 3.25 to 8.94)) and in HLA-B27 negative (OR 2.16 (95% CI 1.04 to 4.51)) patients.
Five-year progression of X-SIJ damage in patients with recent onset axSpA is limited but present beyond measurement error. Baseline MRI-SIJ inflammation drives 5-year radiographic changes.
To describe the prevalence of fibromyalgia (FM) in an axial spondyloarthritis (axSpA) population and to confirm that concomitant FM had a negative impact on tumour necrosis factor blockers' (TNFb) ...response.
Prospective observational study with two visits 3 months apart.
Adult patients with AxSpa initiating a TNFb.
FM was defined by the Fibromyalgia Rapid Screening Tool (FiRST) at baseline and also by a sustained positive FiRST (both visits) and by a fulfilment of the 1990 American College of Rheumatology criteria for FM.
Prevalence of FM; evaluation of the impact of a concomitant FM on TNFb response (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI 50) as primary endpoint), adjusted by factors known to have an impact on TNFb response.
Among the 508 patients included in the main analysis, 192 (37.8%) were screened at baseline as FM. Percentage of success after 12 weeks of treatment was lower in the FM group for most of the effectiveness endpoints (eg, BASDAI 50: 45.3% vs 54.1% in the FM/not FM groups according to the FiRST), except for the C reactive protein change endpoints which were not different across groups.
This study confirms that FM coexists in patients with axSpA and that its presence seems to have a negative impact on TNFb response, which seems more related to the self-reported instruments used in its evaluation, rather than a different treatment effect of the molecule in this subgroup of patients.
Objective
Flares in rheumatoid arthritis (RA) and axial spondyloarthritis (SpA) may influence physical activity. The aim of this study was to assess longitudinally the association between ...patient‐reported flares and activity‐tracker–provided steps per minute, using machine learning.
Methods
This prospective observational study (ActConnect) included patients with definite RA or axial SpA. For a 3‐month time period, physical activity was assessed continuously by number of steps/minute, using a consumer grade activity tracker, and flares were self‐assessed weekly. Machine‐learning techniques were applied to the data set. After intrapatient normalization of the physical activity data, multiclass Bayesian methods were used to calculate sensitivities, specificities, and predictive values of the machine‐generated models of physical activity in order to predict patient‐reported flares.
Results
Overall, 155 patients (1,339 weekly flare assessments and 224,952 hours of physical activity assessments) were analyzed. The mean ± SD age for patients with RA (n = 82) was 48.9 ± 12.6 years and was 41.2 ± 10.3 years for those with axial SpA (n = 73). The mean ± SD disease duration was 10.5 ± 8.8 years for patients with RA and 10.8 ± 9.1 years for those with axial SpA. Fourteen patients with RA (17.1%) and 41 patients with axial SpA (56.2%) were male. Disease was well‐controlled (Disease Activity Score in 28 joints mean ± SD 2.2 ± 1.2; Bath Ankylosing Spondylitis Disease Activity Index score mean ± SD 3.1 ± 2.0), but flares were frequent (22.7% of all weekly assessments). The model generated by machine learning performed well against patient‐reported flares (mean sensitivity 96% 95% confidence interval (95% CI) 94–97%, mean specificity 97% 95% CI 96–97%, mean positive predictive value 91% 95% CI 88–96%, and negative predictive value 99% 95% CI 98–100%). Sensitivity analyses were confirmatory.
Conclusion
Although these pilot findings will have to be confirmed, the correct detection of flares by machine‐learning processing of activity tracker data provides a framework for future studies of remote‐control monitoring of disease activity, with great precision and minimal patient burden.
To determine whether subjective components of disease activity are associated with heterogeneity in opioid prescription in inflammatory rheumatic diseases (IRDs) after accounting for objective ...inflammatory markers.
Data from two prospective observational cohorts of early IRDs (ESPOIR for rheumatoid arthritis (RA) and DESIR for spondyloarthritis (SpA)) were included. Opioid prescription duration (converted to monthly binary opioid prescription), disease activity (Disease activity score 28 (DAS28) for RA; Axial spondyloarthritis disease activity score-C-reactive protein (ASDAS-CRP) for SpA) and its components were measured respectively at 13 and 9 occasions spanning 10- and 6-years of follow-up. Group-based trajectory modelling defined opioid-prescription trajectories and mixed-models characterised the evolution of disease activity and its subjective components by opioid-prescription trajectories.
Four distinct opioid-prescription trajectories: no/low (60.5% and 54.3%), declining (14.7% and 15.8%), augmenting (11.9% and 10.7%), and persistent (12.9% and 19.1%) were identified in RA and SpA respectively (60% were prescribed opioids at least once). Those with regular opioid prescriptions (up to 30%) are often older, less educated, have higher BMI and worse disease. No/low trajectory was the reference for examining evolution of disease activity and subjective components (n=810 RA, n=679 SpA). In IRDs, consistently higher disease activity throughout follow-up were seen with persistent (DAS28(β=0.4-0.8); ASDAS-CRP(β=0.4-0.6)), and augmenting (DAS28(β=0.2-0.5); ASDAS-CRP(β=0.3-0.6)) trajectories and until 3- or 4-years of follow-up (DAS28(β=0.3-0.4); ASDAS-CRP(β=0.2-0.3)) with declining trajectory. Likewise, despite accounting for objective inflammation, subjective components had worse scores over follow-up in augmenting and persistent trajectory.
Non-inflammatory pain mechanisms amplify subjective outcomes, thus, worsening composite measures like disease activity.
To compare the clinical manifestations, disease activity and disease burden between patients with radiographic (r-axSpA) and non-radiographic axial spondyloarthritis (nr-axSpA) over a 5-year ...follow-up period in the Devenir des Spondylarthropathies Indifferénciées Récentes (DESIR) cohort.
Patients from the DESIR cohort who had X-ray images of the sacroiliac joints available at baseline and did not leave the study during the 5-year follow-up period because of a diagnosis other than axSpA were included. A unilateral rating of 'obvious sacroiliitis' by the local reader was considered sufficient for classification as r-axSpA. The incidence of first episodes of peripheral and extra-rheumatic manifestations was compared between the two groups using the incidence rate ratio and Cox regressions adjusted for sex, age and tumour necrosis factor blocker (TNFb) intake. Mean values of patient-reported outcomes (PROs) and days of sick leave over 5 years of follow-up were compared using mixed models adjusted for sex, age, TNFb intake and baseline values.
In total, 669 patients were included, of whom 185 (27.7%) and 484 (72.3%) were classified as r-axSpA and nr-axSpA, respectively. At baseline, the r-axSpA patients showed a significantly higher prevalence of males. After adjusting for age, sex and TNFb intake, Cox regressions for peripheral and extra-rheumatic manifestations did not show any significant differences between groups. Mixed models also showed similar mean levels in PROs and days of sick leave between groups over time.
The incidence of peripheral and extra-rheumatic manifestations as well as the disease burden over time remained similar between r-axSpA and nr-axSpA groups after adjusting for intermediate variables.
NCT01648907.
Increased risk of some comorbidities has been reported in spondyloarthritis (SpA). Recommendations for detection/management of some of these comorbidities have been proposed, and it is known that a ...gap exists between these and their implementation in practice.
To evaluate (1) the prevalence of comorbidities and risk factors in different countries worldwide, (2) the gap between available recommendations and daily practice for management of these comorbidities and (3) the prevalence of previously unknown risk factors detected as a result of the present initiative.
Cross-sectional international study with 22 participating countries (from four continents), including 3984 patients with SpA according to the rheumatologist.
The prevalence of comorbidities (cardiovascular, infection, cancer, osteoporosis and gastrointestinal) and risk factors; percentage of patients optimally monitored for comorbidities according to available recommendations and percentage of patients for whom a risk factor was detected due to this study.
The most frequent comorbidities were osteoporosis (13%) and gastroduodenal ulcer (11%). The most frequent risk factors were hypertension (34%), smoking (29%) and hypercholesterolaemia (27%). Substantial intercountry variability was observed for screening of comorbidities (eg, for LDL cholesterol measurement: from 8% (Taiwan) to 98% (Germany)). Systematic evaluation (eg, blood pressure (BP), cholesterol) during this study unveiled previously unknown risk factors (eg, elevated BP (14%)), emphasising the suboptimal monitoring of comorbidities.
A high prevalence of comorbidities in SpA has been shown. Rigorous application of systematic evaluation of comorbidities may permit earlier detection, which may ultimately result in an improved outcome of patients with SpA.
The association between psoriatic arthritis (PsA) and psoriasis is well known, but some have suggested that other musculoskeletal (MSK) conditions might also be more common in patients with skin ...psoriasis compared with the general population. The aim of our study was to describe the prevalence of a large panel of MSK conditions, in consecutive patients with psoriasis according to skin phenotype. This was a cross-sectional study. We consecutively included 148 patients, consulting for their skin psoriasis, in the dermatology department of a tertiary hospital, Hospital Cochin in Paris, France. After the scheduled consultation with a dermatologist, a rheumatologist conducted a dedicated face-to-face interview to collected data, included demographics, comorbidities, information about the psoriasis, the MSK conditions and their treatments. Of the 148 patients, 122 (82%) had at least one MSK condition. The most common condition was mechanical back pain, present in 98 (66%) patients. Nineteen (13%) patients had spondyloarthritis (SpA), of which 95% had PsA. For all MSK conditions, the dominant psoriasis phenotype was psoriasis vulgaris. The prevalence of the other phenotypes of psoriasis differed by disease. In SpA patients, the three predominant psoriasis phenotypes were: psoriasis vulgaris (82%), scalp involvement (76%) and inverse psoriasis (65%). For all MSK diseases, the prevalence was higher than expected in the general population. Our data suggest that skin psoriasis is associated with different MSK diseases, and not only PsA.
To update French Society for Rheumatology recommendations about the management in clinical practice of patients with spondyloarthritis (SpA). SpA is considered across the range of clinical phenotypes ...(axial, peripheral, and entheseal) and concomitant manifestations. Psoriatic arthritis is included among the SpA phenotypes.
According to the standard procedure advocated by the EULAR for developing recommendations, we first reviewed the literature published since the previous version of the recommendations issued in June 2013. A task force used the results to develop practice guidelines, which were then revised and graded using AGREE II.
Four general principles and 15 recommendations were developed. The first four recommendations deal with treatment goals and general considerations (assessment tools and comorbidities). Recommendations 5 and 6 are on non-pharmacological treatments. Recommendation 7 is about nonsteroidal anti-inflammatory drugs, which are the cornerstone of the treatment, and recommendations 8 to 10 are on analgesics, glucocorticoid therapy, and conventional disease-modifying antirheumatic drugs. Biologics are the focus of recommendations 11 through 14, which deal with newly introduced drug classes, including their indications (active disease despite conventional therapy and, for nonradiographic axial SpA, objective evidence of inflammation) and monitoring, and with patient management in the event of treatment failure or disease remission. Finally, recommendation 15 is about surgical treatments.
This update incorporates recent data into a smaller number of more simply formulated recommendations, with the goal of facilitating their use for guiding the management of patients with SpA.
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