Sharp-van Der Heijde Research Articles

Routine radiographs of hands and feet do not have diagnostic or prognostic value in patients with clinically suspect arthralgia: a large longitudinal study

BackgroundConventional radiographs of hands and feet are used to depict structural damage in rheumatoid arthritis (RA). This is also commonly done in clinical practice in symptomatic patients at risk for...

Remission versus low disease activity as treatment targets in rheumatoid arthritis: how to strike the right balance between too strict and too lenient targets? A meta-epidemiological study of individual patient data

ObjectivesTo evaluate the impact of using Simplified Disease Activity Index (SDAI)-LDA (low disease activity) versus different definitions of remission as a treatment target in established rheumatoid arthritis.MethodsA meta-epidemiological study of...

Can eye-tracking help to create a new method for X-ray analysis of rheumatoid arthritis patients, including joint segmentation and scoring methods?

Reading hand and foot X-rays in rheumatoid arthritis patients is difficult and time-consuming. In research, physicians use the modified Sharp van der Heijde Sharp (mvdH) score by reading of hand and foot radiographs. The aim of this study was to create a new method of determining the mvdH via eye tracking and to study its concordance with the mvdH score. We created a new method of quantifying the mvdH score based on reading time of a reader monitored via eye tracking (Tobii Pro Lab software) after training with the aid of a metronome. Radiographs were read twice by the trained eye-tracking reader and once by an experienced reference radiologist. A total of 440 joints were selected; 416 could be interpreted for erosion, and 396 could be interpreted for joint space narrowing (JSN) when read by eye tracking (eye tracking could not measure the time spent when two pathological joints were too close together). The agreement between eye tracking mvdH Sharp score and classical mvdH Sharp score yes (at least one erosion or JSN) versus no (no erosion or no JSN) was excellent for both erosions (kappa 0.97; 95% CI: 0.96-0.99) and JSN (kappa: 0.95; 95% CI: 0.93-0.097). This agreement by class (0 to 10) remained excellent for both erosions (kappa 0.82; 95% CI: 0.79-0.0.85) and JSN (kappa: 0.68; 95% CI: 0.65-0.0.71). To conclude, eye-tracking reading correlates strongly with classical mvdH-Sharp and is useful for assessing severity, segmenting joints and establishing a rapid score for lesions.

Multimodal Imaging of Structural Damage and Inflammation in Psoriatic Arthritis: A comparison of DMARD-Naive and DMARD-Failure Patients.

To compare inflammatory and structural differences in active Psoriatic Arthritis (PsA) between disease-modifying antirheumatic drug (DMARD)-naive and DMARD-failure patients using diverse imaging approaches for future analyses. Additionally, to explore the influence of patient characteristics (clinical and demographic variables) on imaging findings. Of the 80 patients included from the first cohort of the ongoing multicentre TOFA-PREDICT trial, 40 were DMARD-naive and 40 were DMARD-failure (csDMARD failure; 1 prior bDMARD excluding etanercept was allowed), all meeting classification criteria for PsA with a minimum disease duration of eight weeks. Baseline conventional radiographs of hands and feet, MRIs of both ankles, and whole-body 18F-FDG PET/CT were evaluated for inflammatory and structural imaging parameters, including Sharp-van der Heijde (SHS), Heel Enthesitis Magnetic Resonance Imaging Scoring System (HEMRIS) and Deauville synovitis scoring. Differences between groups and the influence of patient characteristics were examined with multiple linear regression. At baseline, patient characteristics were similar between groups. Imaging parameters showed limited inflammation and structural damage. Inflammatory imaging parameters were not significantly different (p> 0.200). Among structural parameters, only HEMRIS Achilles tendon structural damage was significantly different (p= 0.024, R2=0.071) and, SHS Joint Space Narrowing was not statistically significant (p= 0.050, R2=0.048) with higher values for both in DMARD-failures. After correction of patient characteristics, these differences in imaging disappeared (both p> 0.600). At baseline, PsA patient groups were comparable concerning structural and inflammatory imaging parameters, especially after correcting for patient characteristics. Thus, DMARD-naive and DMARD-failure patient groups may be combined in future PsA progression and treatment decision studies. EudraCT: 2017-003900-28.

Ultrasonographic Synovitis Is Associated with the Development of Joint Destruction in Patients with Psoriatic Arthritis.

Psoriatic arthritis (PsA) is characterized by enthesitis. As persistent inflammation around joints results in bone and cartilage destruction and physical impairment, a detailed assessment of inflammation is essential. We previously reported the difference between clinical assessment (tenderness) and ultrasound (US) assessment (inflammation) of entheses. Herein, we investigated whether clinical or US assessment of joints and entheses can predict the progression of joint destruction in Japanese patients with PsA. Thirty joints and 14 entheses in 47 patients were assessed using US and clinical examination. The US greyscale (GS) and power Doppler (PD) scores at the ultrasonographic synovitis, the US active enthesitis count, and the clinical tender joint/entheses count were assessed. Additionally, the yearly radiographic progression of the Sharp-van der Heijde scoring method for PsA was assessed. Their correlations were investigated. About half of the patients with PsA experienced joint destruction during a follow-up period of 20.4 months. Progression of joint destruction in patients with PsA only correlated with joint GS and PD scores, reflecting the severity of ultrasonographic synovitis, not with the tender joint/entheses count. US examinations are essential for preventing joint destruction and physical impairment in patients with PsA.

Adding ultrasound to treat-to-target shows no benefit in achieving clinical remission nor in slowing radiographic progression in rheumatoid arthritis: results from a multicenter prospective cohort.

To assess whether using ultrasound (US) in addition to clinical information versus only clinical information in a treat-to-target (T2T) strategy leads to more clinical remission and to less radiographic progression in RA. Patients with RA from the 2-year prospective BIODAM cohort were included. Clinical and US data (US7-score) were collected every 3months and hands and feet radiographs every 6months. At each visit, it was decided whether patients were treated according to the clinical definition of T2T with DAS44 remission as benchmark (T2T-DAS44). T2T-DAS44 was correctly applied if: (i) DAS44 remission had been achieved or (ii) if not, treatment was intensified. A T2T strategy also considering US data (T2T-DAS44-US) was correctly applied if: (i) both DAS44 and US remission (synovitis-score < 2, Doppler-score = 0) were present; or (ii) if not, treatment was intensified. The effect of T2T-DAS44-US on attaining clinical remission and on change in Sharp-van der Heijde score compared to T2T-DAS44 was analysed. A total of 1016 visits of 128 patients were included. T2T-DAS44 was correctly followed in 24% of visits and T2T-DAS44-US in 41%. DAS44 < 1.6 was achieved in 39% of visits. Compared to T2T-DAS44, using the T2T-DAS44-US strategy resulted in a 41% lower likelihood of DAS44 remission [OR (95% CI): 0.59 (0.40;0.87)] and had no effect on radiographic progression [β(95% CI): 0.11 (- 0.16;0.39)] assessed at various intervals up to 12months later. Our results do not suggest a benefit of using the US7-score in addition to clinical information as a T2T benchmark compared to clinical information alone. Key Points • Ultrasound has a valuable role in diagnostic evaluation of rheumatoid arthritis, but it is unclear whether adding ultrasound to the clinical assessment in a treat-to-target (T2T) strategy leads to more patients achieving remission and reduction in radiographic progression. • Our data from a real-world study demonstrated that adding information from ultrasound to the clinical assessment in a T2T strategy led to a lower rather than a higher likelihood of obtaining clinical remission as compared to using only clinical assessment. • Our data demonstrated that adding ultrasound data to a T2T strategy based only on clinical assessment did not offer additional protection against radiographic progression in patients with RA. • Adding US to a T2T strategy based on clinical assessment led to far more treatment intensifications (with consequences for costs and exposure to adverse events) without yielding a meaningful clinical benefit.

Deep Learning Enables Automatic Detection of Joint Damage Progression in Rheumatoid Arthritis-Model Development and External Validation.

Although deep learning has demonstrated substantial potential in automatic quantification of joint damage in rheumatoid arthritis (RA), evidence for detecting longitudinal changes at an individual patient level is lacking. Here, we introduce and externally validate our automated RA scoring algorithm (AuRA), and demonstrate its utility for monitoring radiographic progression in a real-world setting. The algorithm, originally developed during the Rheumatoid Arthritis 2-Dialogue for Reverse Engineering Assessment and Methods (RA2-DREAM) challenge, was trained to predict expert-curated Sharp-van der Heijde total scores in hand and foot radiographs from two previous clinical studies (n = 367). We externally validated AuRA against data (n = 205) from Turku University Hospital and compared the performance against two top-performing RA2-DREAM solutions. Finally, for 54 patients, we extracted additional radiograph sets from another control visit to the clinic (average time interval of 4.6 years). In the external validation cohort, with a root-mean-square-error (RMSE) of 23.6, AuRA outperformed both top-performing RA2-DREAM algorithms (RMSEs 35.0 and 35.6). The improved performance was explained mostly by lower errors at higher expert-assessed scores. The longitudinal changes predicted by our algorithm were significantly correlated with changes in expert-assessed scores (Pearson's R = 0.74, p< 0.001). AuRA had the best external validation performance and demonstrated potential for detecting longitudinal changes in joint damage. Available in https://hub.docker.com/r/elolab/aura, our algorithm can easily be applied for automatic detection of radiographic progression in the future, reducing the need for laborious manual scoring.

Disease activity-guided dose optimisation including discontinuation of TNF-inhibitors in rheumatoid arthritis is effective for up to 10 years: an observational follow-up of the DRESS study.

To investigate safety and effectiveness of disease activity-guided dose optimisation of TNF-inhibitors in rheumatoid arthritis over 10 years. Observational long-term extension of a randomised study of participants who completed the 3-year extension of the DRESS-study. After the randomised phase (month 0-18), disease activity-guided dose optimisation was allowed for all. Main outcomes were mean time-weighted DAS28-CRP; biological and targeted synthetic anti-rheumatic drug (b/tsDMARD) use per year as proportion of daily defined dose; proportion of patients reaching discontinuation; durability, effectiveness of subsequent dose reduction attempts; and radiographic progression between 3 and 10 years using the Sharp-van der Heijde score. 170 patients were included of whom 127 completed 10-year follow-up. The mean disease activity remained low (DAS28-CRP 2.13, 95% confidence interval 2.10-2.16), whilst the b/tsDMARD dose reduced from 97% at baseline (95%CI 96% to 99%, n = 170)% to56% at year 10 (49% to 63%, n = 127). 119 of 161 participants (74%) with an optimisation attempt reached discontinuation, with a median duration of 7 months (interquartile range 3-33 months), and 25 participants never had to restart their b/tsDMARD (21%, 14% to 29%). The mean dose reduction after dose optimisation was 48% (n = 159) for the first optimisation attempt and 33% for subsequent attempt (n = 86). 48% (41/86) of participants had radiographic progression exceeding the smallest detectable change (5.7 units), and progression was associated with disease activity, not b/tsDMARD use. Long-term disease activity-guided dose optimisation of TNF-inhibitors in rheumatoid arthritis, including discontinuation and multiple tapering attempts, remains safe and effective.

Distinction and prognosis of early arthritis phenotypes: an analysis in three European cohorts

ObjectivesThe objective of this study is to evaluate whether there are differences in the long-term prognosis across various phenotypes of early arthritis (EA).MethodsThree EA cohorts (Reade, Etude et Suivi des...

Changes in bone turnover markers and bone modulators during abatacept treatment

Rheumatoid arthritis (RA) causes bone loss, only partly related to inflammation. The impact of RA treatments on bone metabolism and their ability to mitigate bone loss remains uncertain. The primary goal of our study was to examine the influence of abatacept on serum levels of markers and regulators involved in bone turnover. Secondary objectives included evaluating changes in bone mineral density (BMD), bone health parameters, erosions, and exploring potential correlations among these parameters. We conducted a prospective observational study on patients with active seropositive RA failure to biological disease modifying anti-rheumatic drugs initiating treatment with abatacept. We measured at baseline and after 1, 2, 3, 6, 9 and 12 months: serum bone turnover markers (CTX, P1nP, B-ALP), bone modulators (Dkk-1, sclerostin, vitamin D, PTH, OPG and RANKL), BMD and radiographic parameters (modified Sharp van der Heijde score [mSvdH], bone health index [BHI] and metacarpal index [MCI]). Disease activity and glucocorticoid intake was monitored. 33 patients were enrolled in the study. We found a significant increase in markers of bone formation (B-ALP and P1nP) from baseline to M6 and M12. PTH increased significantly at M6 but not at M12. All other bone markers and modulators did not change. We found a significant decrease in BHI and MCI from baseline to M12 (median difference − 0.17 95% CI − 0.42 to − 0.10, p 0.001 and − 0.09 95% CI − 0.23 to − 0.07, respectively). BMD at femoral neck transitorily decreased at M6 (mean difference − 0.019 g/cm2 95% CI − 0.036 to − 0.001 p 0.04). BMD at total hip, lumbar spine and mSvdH score did not change significantly. P1nP delta at M12 correlated with delta mSvdH. Treatment with abatacept was associated with a significant increase in bone formation markers. The secondary and transient increase in PTH serum levels may be responsible of the transitory bone loss.

Comparison of Hand-Wrist Findings of Rheumatoid Arthritis Patients According to the Use of Synthetic and Biological Disease-Modifying Antirheumatic Drugs (DMARDs): A Clinical, Radiographic, and Ultrasonographic Study.

The aim of this study is to evaluate the hand-wrist findings in patients with rheumatoid arthritis (RA) using synthetic and a combination of synthetic and biological disease-modifying antirheumatic drugs (DMARDs) in terms of ultrasonographic, clinical, and radiographic data. The study is designed as a cross-sectional study, and 31 RA patients followed up in the rheumatology outpatient clinic were enrolled. Nineteen patients were using only synthetic DMARDs, and 12 patients were using a combination of synthetic and biological DMARDs. The clinical data of each patient were recorded simultaneously. Disease Activity Score-28 (DAS-28) was used for the assessment of disease activation, and the Health Assessment Questionnaire (HAQ) score was used for the evaluation of general health status. Bilateral proximal interphalangeal (PIP), metacarpophalangeal (MCP) joints, and the radiocarpal, ulnocarpal, and midcarpal joints of the patients were examined by ultrasonography (US). The Sharp-van der Heijde modified score was used to determine the radiographic damage. There was no significant difference between the two groups in terms of demographic data, clinical findings, ESR, and CRP. When the groups were compared in terms of right and left PIP, MCP, and radiocarpal, ulnocarpal, and midcarpal synovitis grade total scores, no significant difference was found between the two groups. Radiographic total joint space scores were significantly lower in the group receiving only synthetic DMARD treatment (p=0.047) and 25-OH vitamin D levels were significantly higher (p=0.008). This study revealed that there was no significant difference between groups except radiographic total joint space scores.

Earlier clinical response predicts low rates of radiographic progression in biologic-naïve patients with active psoriatic arthritis receiving guselkumab treatment

ObjectiveAssess relationship between earlier clinical improvement and radiographic progression (RP) over 2 years in guselkumab-treated patients with active psoriatic arthritis (PsA).MethodPost hoc analyses combined data from DISCOVER-2 biologic-naïve adults with active PsA randomized to either guselkumab 100 mg every 4 weeks (Q4W) or guselkumab at W0, W4, then Q8W. Correlations (Spearman’s coefficient) between baseline disease parameters and total PsA-modified van der Heijde-Sharp (vdH-S) score were examined. Repeated-measures mixed models, adjusted for known RP risk factors, assessed the relationship between Disease Activity Index in PsA (DAPSA) improvement, DAPSA improvement exceeding the median or the minimal clinically important difference (MCID), or DAPSA low disease activity (LDA) at W8 and RP rate, assessed by change from baseline in vdH-S score through W100.ResultsBaseline age, PsA duration, CRP level, and swollen joint count, but not psoriasis duration/severity, weakly correlated with baseline vdH-S score. Elevated baseline CRP (parameter estimate [β] = 0.17–0.18, p < 0.03) and vdH-S score (β = 0.02, p < 0.0001) significantly associated with greater RP through W100. Greater improvement in DAPSA (β = -0.03, p = 0.0096), achievement of DAPSA improvement > median (least squares mean [LSM] difference: -0.66, p = 0.0405) or > MCID (-0.67, p = 0.0610), or DAPSA LDA (-1.44, p = 0.0151) by W8 with guselkumab significantly associated with less RP through W100. The effect of W8 DAPSA LDA on future RP was strengthened over time among achievers vs. non-achievers (LSM difference enhanced from -1.05 [p = 0.0267] at W52 to -1.84 [p = 0.0154] at W100).ConclusionsIn guselkumab-treated patients with active PsA, earlier improvement in joint symptoms significantly associated with lower RP rates through 2 years, indicating blockade of the IL-23 pathway may modify long-term disease course and prevent further joint damage.Key Points• Greater improvement in DAPSA at Week 8 of guselkumab treatment was significantly associated with less progression of structural joint damage at 2 years in patients with active psoriatic arthritis (PsA).• Early control of peripheral joint disease activity with blockade of the IL-23 pathway may modify long-term PsA trajectory and prevent further joint damage.

Elevated serum leptin may be associated with disease activity and secondary osteoporosis in Chinese patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic chronic autoimmune disease in adults that is associated with significant joint issues and systemic inflammation. One of the signs of bone damage in RA is osteoporosis (OP). Leptin is an inflammatory protein that has been reported to be related to RA. The potential relationships among leptin, disease activity, and OP in Chinese patients with RA are not well known. In total, 245 patients with RA and 120 healthy controls were included in this study. Detailed data on the clinical characteristics and laboratory features were collected. Information about physical activity and functional status was recorded using specific questionnaires. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA). The MECALL castor-50-hf model X-ray scanner was used for the two-hand (including wrist) photographs. Serum leptin levels differed significantly between the RA group and healthy control subjects (1.27/3.29 vs. 0.17/0.24, Z=13.29, P<0.001). The positive rate of leptin protein in RA patients was 86.35%, which was higher than that in controls (19.55%) (χ2=28.51, P<0.001). Pearson's correlation test showed that morning stiffness, disease duration, joint swelling, joint tenderness, swollen joint count (SJC), tender joint count (TJC), health assessment questionnaire (HAQ) score, and Sharp-van der Heijde method (Sharp) score were positively correlated with the level of serum leptin (r=0.212, r=0.312, r=0.322, r=0.501, r=0.291, r=0.334, P<0.05). There was a clear increasing trend in the level of serum leptin according to the different disease activity scores and in the 28 joint activity (DAS28) groups (F=13.936, P<0.001). Elevated leptin was a risk factor for increased disease activity and OP according to logistic regression analysis. The median leptin level differed significantly between the normal bone mass group, osteopenia group, and OP group (P<0.001). An increased serum leptin level was a risk factor for RA-induced osteoporosis according to logistic regression analysis (P<0.001). These results suggest that the level of serum leptin is associated with disease activity and secondary OP among Chinese patients with RA. Key Points • Serum leptin levels in RA patients are higher than those in normal control group. • Leptin was associated with disease activity. • Leptin was associated with the occurrence of systemic osteoporosis and affects bone erosion in RA patients.

The association between Disease Activity Score and rheumatoid arthritis-associated cervical deformity: radiological evaluation of the BeSt trial.

The authors' objective was to evaluate the association of the Disease Activity Score (DAS) with cervical spine deformity in rheumatoid arthritis (RA) patients during 10-year optimal treatment of systemic disease. The authors evaluated radiological and 10-year follow-up (FU) data of the BeSt (BehandelStrategien) trial. In 272 RA patients, atlantoaxial subluxation (AAS), presence of vertical translocation (VT), and subaxial subluxation (SAS) were evaluated. The associations of these deformities with DAS, self-assessed health (determined with the Health Assessment Questionnaire [HAQ]), and erosions of the hands and feet (Sharp-Van der Heijde score) were studied. After 10 years of FU, AAS (> 2 mm neutral position) was observed in 62 patients (23%), AAS (≥ 3 mm in flexion) in 24%, AAS (≥ 5 mm in flexion) in 7%, VT did not occur, and SAS was present in 60 patients (22%). In total, 135 patients (50%) were in remission (DAS < 1.6) at 10 years of FU. No association could be established between AAS and DAS. Patients with cervical spine deformity (AAS > 2 mm and/or SAS) at 10 years had a higher HAQ score at 10 years than patients without cervical spine deformity (HAQ scores of 0.65 and 0.51, respectively, p = 0.04; 95% CI -0.29 to 0.00). Even though 50% of patients were in remission after 10 years and the BeSt trial was designed to optimize treatment, 40% of patients developed at least mild RA-associated cervical spine deformity and 7% developed significant AAS. This indicates that even in this era of disease-modifying antirheumatic drugs and biologicals, cervical deformity is prevalent among patients with RA and should not be neglected in patient treatment plans and information.

Risk stratification using anti-citrullinated peptide antibodies (ACPA) in polyarticular subtypes of juvenile idiopathic arthritis in adulthood.

Polyarticular juvenile idiopathic arthritis (pJIA) is a subset of juvenile idiopathic arthritis (JIA), divided into two subtypes according to the presence of rheumatoid factor : pJIA without rheumatoid factor (pJIA RF-) and pJIA with positive rheumatoid factor (pJIA RF+), this latter is characterised with more structural damage. Anti-citrullinated peptide antibodies (ACPA) are often associated with RF. The respective performance of ACPA versus RF in structural outcome in pJIA, and in particular in adulthood pJIA remains unknown. Therefore, the aim of this study was to determine whether ACPA could be of value to assess structural damage in pJIA persisting in adulthood. Patients with pJIA and available data for ACPA, RF and X-ray were included retrospectively. Structural damage was assessed by two independent blinded investigators using Sharp Van Der Heijde scores. 56 pJIA adult patients were included : 62% (35/56) had pJIA RF+ and 38% (21/56) pJIA RF-. ACPA positivity in pJIA was significantly associated with presence of RF (96% vs 26%, p<0.001 ). RF positivity was significantly associated with higher Sharp van Der Heijde erosion and total scores (respectively p< 0.01 and p< 0.05 ). There were higher Sharp Van Der Heijde erosion, joint space narrowing and total scores in the pJIA ACPA+ subgroup than in the pJIA ACPA- subgroup, although there was no statistical significance. However, when adjusted on disease duration, pJIA ACPA+ patients had significantly higher erosion and total scores than pJIA ACPA- patients (p<0.05), and pJIA ACPA+ patients required more bDMARDs than pJIA ACPA- patients (p<0.05). Moreover, pJIA patients with high Sharp van Der Heijde joint space narrowing and total scores had significantly higher ACPA levels (p<0.01). A correlation was identified between ACPA levels and Sharp van Der Heijde total score ( r=0.54, p<0.05). In the pJIA RF+ subgroup the presence of ACPA was associated with additional structural damage compared to no ACPA: sharp Van Der Heijde erosion, joint space narrowing and total scores were higher in the pJIA RF+ ACPA+ subgroup than in the pJIA RF+ ACPA- subgroup although these results did not reach significance. Our results suggest that pJIA RF+ ACPA+ adult patients may have a more severe articular phenotype than pJIA RF+ ACPA- patients. ACPA could bring an additional value to RF for pJIA patients regarding structural damage. Altogether our results show that RF and ACPA are associated with structural damage measured by Sharp Van Der Heijde score in pJIA persisting in adulthood.

Radiographic damage in early rheumatoid arthritis is associated with increased disability but not with pain—a 5-year follow-up study

ObjectivesTo evaluate how radiographic damage, overall and measured as joint space narrowing score (JSNS) and erosion score (ES), as well as other clinical and laboratory measures, relate to disability and pain in early rheumatoid arthritis (RA).MethodsAn inception cohort of 233 patients with early RA, recruited in 1995–2005, was followed for 5 years. Disability was assessed with the Health Assessment Questionnaire (HAQ), and pain with a visual analogue scale (VAS; 0–100 mm). Radiographs of hands and feet were evaluated using the Sharp-van der Heijde score (SHS), including JSNS and ES. The relation for radiographic scores and other clinical parameters with pain and HAQ were evaluated cross-sectionally by multivariate linear regression analysis and over time using generalized estimating equations.ResultsES was significantly associated with HAQ cross-sectionally at inclusion, after 2 and after 5 years, and over time. Associations for HAQ with SHS and JSNS were weaker and less consistent compared with those for ES. There was no association between radiographic scores and pain at any visit. Both HAQ and pain were associated with parameters of disease activity. The strongest cross-sectional associations were found for the number of tender joints (adjusted p<0.001 at all visits).ConclusionJoint damage was associated with disability already in early RA. Erosions of hands and feet appear to have a greater influence on disability compared with joint space narrowing early in the disease. Pain was associated with other factors than joint destruction in early RA, in particular joint tenderness—suggesting an impact of pain sensitization.

Safety and efficacy associated with long-term low-dose glucocorticoids in rheumatoid arthritis: a systematic review and meta-analysis.

The aim of this study was to assess the safety and efficacy of long-term low-dose glucocorticoids (GCs) in RA. A protocolised systematic review and meta-analysis (PROSPERO No. CRD42021252528) of double-blind, placebo-controlled randomised trials (RCTs) comparing a low dose of GCs (≤ 7.5mg/day prednisone) to placebo over at least 2 years was performed. The primary outcome investigated was adverse events (AEs). We performed random-effects meta-analyses and used the Cochrane RoB tool and GRADE to assess risk of bias and quality of evidence (QoE). Six trials with 1078 participants were included. There was no evidence of an increased risk of AEs (incidence rate ratio 1.08; 95% CI 0.86, 1.34; P = 0.52); however, the QoE was low. The risks of death, serious AEs, withdrawals due to AEs, and AEs of special interest did not differ from placebo (very low to moderate QoE). Infections occurred more frequently with GCs (risk ratio 1.4; 1.19-1.65; moderate QoE). Concerning benefit, we found moderate to high quality evidence of improvement in disease activity (DAS28: -0.23; -0.43 to -0.03), function (HAQ -0.09; -0.18 to 0.00), and Larsen scores (-4.61; -7.52 to -1.69). In other efficacy outcomes, including Sharp van der Heijde scores, there was no evidence of benefits with GCs. There is very low to moderate QoE for no harm with long-term low dose GCs in RA, except for an increased risk of infections in GC users. The benefit-risk ratio might be reasonable forusing low-dose long-term GCs considering the moderate to high quality evidence for disease-modifying properties.

Low rates of radiographic progression associated with clinical efficacy following up to 2 years of treatment with guselkumab: results from a phase 3, randomised, double-blind, placebo-controlled study of biologic-naïve patients with active psoriatic arthritis

ObjectiveEvaluate relationship between radiographic progression and clinical outcomes in post hoc analyses of patients with psoriatic arthritis (PsA) receiving up to 2 years of guselkumab therapy in the phase 3,...

Stricter treat-to-target in RA does not result in less radiographic progression: a longitudinal analysis in RA BIODAM.

To investigate whether meticulously following a treat-to-target (T2T)-strategy in daily clinical practice will lead to less radiographic progression in patients with active RA who start (new) DMARD-therapy. Patients with RA from 10 countries starting/changing conventional synthetic or biologic DMARDs because of active RA, and in whom treatment intensification according to the T2T principle was pursued, were assessed for disease activity every 3 months for 2 years (RA-BIODAM cohort). The primary outcome was the change in Sharp-van der Heijde (SvdH) score, assessed every 6 months. Per 3-month interval DAS44-T2T could be followed zero, one or two times (in a total of two visits). The relation between T2T intensity and change in SvdH-score was modelled by generalized estimating equations. In total, 511 patients were included [mean (s.d.) age: 56 (13) years; 76% female]. Mean 2-year SvdH progression was 2.2 (4.1) units (median: 1 unit). A stricter application of T2T in a 3-month interval did not reduce progression in the same 6-month interval [parameter estimates (for yes vs no): +0.15 units (95% CI: -0.04, 0.33) for 2 vs 0 visits; and +0.08 units (-0.06; 0.22) for 1 vs 0 visits] nor did it reduce progression in the subsequent 6-month interval. In this daily practice cohort, following T2T principles more meticulously did not result in less radiographic progression than a somewhat more lenient attitude towards T2T. One possible interpretation of these results is that the intention to apply T2T already suffices and that a more stringent approach does not further improve outcome.

The effect of guselkumab on inhibiting radiographic progression in patients with active psoriatic arthritis: study protocol for APEX, a Phase 3b, multicenter, randomized, double-blind, placebo-controlled trial

BackgroundGuselkumab, a fully human monoclonal antibody targeting the interleukin (IL)-23p19 subunit, is approved to treat adults with active psoriatic arthritis (PsA). In the Phase 3 DISCOVER-2 trial of 739 bilogico-naïve patients with active PsA, guselkumab 100 mg resulted in less radiographic progression, assessed via change from baseline in PsA-modified van der Heijde-Sharp (vdH-S) score, compared with placebo at week (W) 24 when given at W0, W4, and then every 4 weeks (Q4W) or Q8W. The least squares mean differences from placebo were -0.66 for guselkumab Q4W (p=0.011) and -0.43 for guselkumab Q8W (p=0.072). Reports suggest baseline C-reactive protein (CRP) and joint erosions are strongly prognostic of poor outcomes, especially radiographic progression, in PsA patients. We designed a trial (APEX) to further assess the effect of guselkumab on radiographic progression in patients with active PsA and risk factors for radiographic progression.MethodsPatients are eligible for APEX if they have had PsA for ≥6 months and active disease (≥3 swollen and ≥3 tender joints, CRP ≥0.3 mg/dL) despite prior therapy with conventional synthetic disease-modifying antirheumatic drugs, apremilast, and/or nonsteroidal anti-inflammatory drugs, with ≥2 joints with erosions on baseline radiographs (hands and feet). The primary and major secondary endpoints are the proportion of patients achieving ≥20% improvement in American College of Rheumatology response criteria (ACR20) response at W24 and change from baseline at W24 in PsA-modified vdH-S score, respectively. Sample sizes of 350/250/350 for guselkumab Q8W/guselkumab Q4W/placebo are expected to provide >99% power to detect significant differences in W24 ACR20 response rates for each guselkumab group vs placebo, as well as ≥90% (Q4W vs placebo) and ≥80% (Q8W vs placebo) power to detect a significant difference in PsA-modified vdH-S score change at W24. A Cochran-Mantel-Haenszel test and analysis of covariance will compare treatment efficacy for the primary and major secondary endpoints, respectively.DiscussionDISCOVER-2 findings informed the design of APEX, a Phase 3b study intended to further evaluate the impact of guselkumab in patients with active PsA and known risk factors for radiographic progression.Trial registrationThis trial was registered at ClinicalTrials.gov, NCT04882098. Registered on 11 May 2021.