Abstract

Objective:

Recommendations regarding “treat to target” in psoriatic arthritis (PsA) have stated that the target should be remission or inactive disease. Potential definitions include very low disease activity (VLDA), PsA Disease Activity Score (PASDAS) near remission, Disease Activity Index for PsA (DAPSA) or clinical DAPSA (cDAPSA) remission. Our aim was to investigate the proportion of patients who fulfill these definitions and how much residual active disease remained.

Methods:

This analysis used 2 datasets: first, trial data from the Tight Control of PsA (TICOPA) study, which included 206 patients with recent-onset (< 2 yrs) PsA receiving standard and biological disease-modifying antirheumatic drugs (DMARD); and second, an observational clinical dataset from Italy of patients receiving biological DMARD. Proportions achieving each of the 4 potential targets were calculated in each dataset and comparisons between treatment groups were performed in the TICOPA dataset. Levels of residual disease were established for key clinical domains of PsA.

Results:

All measures could differentiate the TICOPA trial treatment groups (p < 0.03). Lower proportions of patients fulfilled the VLDA criteria compared to DAPSA or cDAPSA remission. PASDAS results were different between the cohorts. Residual active disease was low across all definitions although higher levels were seen in DAPSA and cDAPSA compared to VLDA, particularly for psoriasis. In all measures, the proportion with elevated C-reactive protein was similar and low.

Conclusion:

VLDA appears the most stringent measure. It ensures that significant active arthritis, enthesitis, and psoriasis are not present, in contrast with DAPSA and PASDAS, in which composite scores can “hide” active disease in some domains.

Vai al full paper 

Abstract

Over the past several years, a pathophysiological role for the IL-23-IL-17 pathway in human disease has been defined. A subset of rheumatic diseases, including psoriatic arthritis (PsA) and ankylosing spondylitis (AS), are now acknowledged to be triggered by dysregulated IL-23-IL-17 pathway activation. Genetic evidence links the IL-23-IL-17 pathway to inflammation in these rheumatic diseases, and mechanistic data from mice support a functional role for IL-23-IL-17 pathway activation in the development of enthesitis and in entheseal bone formation. Furthermore, analysis of human tissue samples, as well as data from clinical trials, also supports a role for activation of the IL-23-IL-17 pathway in these diseases. The unique bone phenotype that occurs in PsA and AS is a surprising coexistence of both systemic bone loss and periosteal and entheseal bone formation and is likely to be the result of the actions of IL-23 and/or IL-17 on bone. However, the effects of these cytokines on bone cells are complex, and controversy remains regarding their exact roles in the specific bone microenvironments relevant to PsA and AS.

Vai all’abstract

Abstract

Objectives:

To evaluate the effect of subcutaneous (s.c.) secukinumab, an interleukin-17A inhibitor, on clinical signs and symptoms and radiographic progression in patients with psoriatic arthritis (PsA).

Methods:

Adults (n=996) with active PsA were randomised 2:2:2:3 to s.c. secukinumab 300 mg or 150 mg with loading dose (LD), 150 mg without LD or placebo. All groups received secukinumab or placebo at baseline, weeks 1, 2 and 3 and then every 4 weeks from week 4. The primary endpoint was the proportion of patients achieving an American College of Rheumatology 20 (ACR20) response at week 16.

Results:

Significantly more patients achieved an ACR20 response at week 16 with secukinumab 300 mg with LD (62.6%), 150 mg with LD (55.5%) or 150 mg without LD (59.5%) than placebo (27.4%) (p<0.0001 for all; non-responder imputation). Radiographic progression, as measured by van der Heijde-modified total Sharp score, was significantly inhibited at week 24 in all secukinumab arms versus placebo (p<0.01 for 300 mg with LD and 150 mg without LD and p<0.05 for 150 mg with LD; linear extrapolation). Adverse event rates at week 24 were similar across treatment arms: 63.1% (300 mg with LD), 62.7% (150 mg with LD), 61.1% (150 mg without LD) and 62.0% (placebo). No deaths or new safety signals were reported.

Conclusions:

S.c. secukinumab 300 mg and 150 mg with and without LD significantly improved clinical signs and symptoms and inhibited radiographic structural progression versus placebo at week 24 in patients with PsA.

Vai al Full Paper

Abstract

Background

Nail psoriasis is associated with functional impairment, pain and reduced quality of life.

Objective

To demonstrate the superiority of secukinumab vs. placebo in clearing nail psoriasis as assessed by NAil Psoriasis Severity Index (NAPSI) at Week 16 and over time up to Week 132. Presented here is the Week 32 interim analysis. Impact on quality of life was assessed by Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) patient questionnaires.

Methods

TRANSFIGURE is a double‐blind, randomized, placebo‐controlled study in subjects with moderate to severe plaque and nail psoriasis.

Results

The primary objective of this study was met: both doses of secukinumab were superior to placebo at Week 16 (NAPSI improvement of ‐45.3%, ‐37.9%, and ‐10.8%, for secukinumab 300 mg, 150 mg and placebo, respectively, P<0.0001). Significant improvements were seen in patients’ quality of life: NAPPA‐QOL total score median decrease at Week 16 was 60.9%, 49.9% and 15.8% for secukinumab 300 mg, 150 mg and placebo, respectively (P<0.0001). Improvement in nail psoriasis continued to Week 32: NAPSI % change reached ‐63.2% and ‐52.6%, for secukinumab 300 mg and 150 mg, respectively. Skin clearance was significant (PASI 90: 72.5%, 54.0% and 1.7% for secukinumab 300 mg, 150 mg and placebo at Week 16, respectively, P<0.0001) and was sustained to Week 32. The most common adverse events were nasopharyngitis, headache, and upper respiratory tract infections.

Conclusions

Secukinumab demonstrated significant and clinically meaningful efficacy and quality of life improvements for patients with nail psoriasis up to Week 32.

Structured Abstract

Purpose:

To review evidence about screening to prevent osteoporotic fractures for the U.S. Preventive Services Task Force (USPSTF).

Data Sources:

PubMed, the Cochrane Library, Embase, and trial registries from November 1, 2009, through October 1, 2016, and surveillance of the literature through March 23, 2018; bibliographies from retrieved articles.

Study Selection:

Two investigators independently selected studies using a priori inclusion and exclusion criteria. We selected studies with a majority of adults age 40 years or older conducted in countries with a very high human development index. For screening studies, we required that studies include a majority of participants without prevalent low-trauma fractures. For treatment studies, we required that studies include a majority of participants with increased fracture risk. We selected studies of screening tests (fracture risk prediction instruments, bone measurement testing, or a combination of fracture risk prediction instruments and bone measurement testing) that were feasible for primary care settings and available in the United States. We selected studies of treatment approved by the U.S. Food and Drug Administration for synthesis of benefits and harms. We excluded studies of poor quality and of fracture risk prediction instruments without external validation.

Data Extraction:

One investigator extracted data and a second checked accuracy. Two reviewers independently rated quality for included studies using predefined criteria.

Data Synthesis:

One fair-quality trial demonstrated reduction in hip fractures when comparing screening with no screening (2.6% v 3.5%, Hazard rate [HR] 0.72; 95% confidence interval [CI], 0.59 to 0.89). The study reported no other statistically significant benefits (osteoporotic or clinical fractures, mortality) or harms (anxiety, quality of life). We included 168 articles of fair or good quality; 105 articles assessed screening accuracy and 65 articles assessed benefits and harms of treatment. Using centrally measured dual-energy X-ray absorptiometry (DXA) as the reference standard for identifying osteoporosis, the pooled estimate of accuracy as measured by the area under the curve (AUC) for clinical risk assessment instruments for women ranges from 0.65 to 0.76 and for men from 0.76 to 0.80. AUCs for the accuracy of calcaneal quantitative ultrasound in identifying central DXA—measured osteoporosis for women is 0.77 (95% CI, 0.72 to 0.82, 7 studies) and for men is 0.80 (95% CI, 0.67 to 0.94, 3 studies). The AUCs of machine-based tests, including centrally measured DXA (areal bone mineral density and trabecular bone score) and calcaneal quantitative ultrasound, for predicting fractures ranged from 0.59 to 0.86 (21 studies). The AUCs for instruments predicting fractures, some of which incorporate machine-based tests, have similar accuracy (pooled AUC range for the Fracture Risk Assessment Tool: 0.62 to 0.79; 24 studies). Available but limited evidence in studies including participants with a wide spectrum of baseline bone mineral density from normal to osteoporosis suggests no benefit from repeating a bone measurement test between 4 and 8 years after the initial screen. Evidence from placebo-controlled trials demonstrates the following benefits. For women, the risk of vertebral fractures can be reduced by bisphosphonates, parathyroid hormone, raloxifene, and denosumab by 36 percent to 68 percent. Relative risks (RRs) range from 0.32 (parathyroid hormone or denosumab) to 0.64 (raloxifene). The risk of nonvertebral fractures can be reduced by 16 percent to 20 percent by bisphosphonates and denosumab (RR, 0.84 and 0.80, respectively). The risk of hip fractures can be reduced by 40 percent by denosumab (RR, 0.60). Evidence from bisphosphonates does not demonstrate benefit for hip fractures. Evidence is very limited for men. The risk of morphometric vertebral fractures can be reduced by 67 percent by zoledronic acid (RR, 0.33). No studies demonstrate reductions in risk of clinical vertebral fractures or hip fractures for men. Evidence on variations in effectiveness for subgroups is also limited; a single trial each for five drugs suggests no differences in effectiveness by age, baseline bone mineral density, prior fractures, or a combination of risk factors. Bisphosphonates are not consistently associated with discontinuations, serious adverse events, gastrointestinal events, or cardiovascular events. No included studies reported cases of osteonecrosis of the jaw or atypical femur fracture, although evidence from excluded studies (including active comparisons, case series, and secondary prevention populations) suggests an increased but rare risk of these outcomes. Raloxifene increases the risk of deep vein thrombosis (0.7% vs. 0.3%, RR, 2.14; 95% CI, 0.99 to 4.66; I2=0%, 3 studies, N=5,839) and hot flashes (11.2% vs. 7.6%, RR, 1.42; 95% CI, 1.22 to 1.66; I2=0%, 5 trials; N=6,249) when compared with placebo.

Limitations:

The evidence is limited on the direct question of the benefits and harms of screening for elevated osteoporotic fracture risk. The indirect evidence pathway rests on studies evaluating (1) the accuracy of screening approaches in identifying osteoporosis and predicting fractures and (2) the benefits of treatment among those with osteoporosis or at high risk for fractures. Other limitations of the evidence base relate to underlying heterogeneity in baseline risk, prior fractures, prior treatment, and duration of followup.

Conclusions:

Evidence from one trial of screening to prevent osteoporotic fractures suggests a reduction in hip fractures. The accuracy of clinical risk assessment tools for identifying osteoporosis or predicting fractures generally ranges from very poor (0.50) to good (0.90). Treatments reduce the risk of vertebral and nonvertebral fractures. Studies do not consistently demonstrate an increased risk of harms for drugs, although studies of raloxifene suggest a trend toward higher risk of deep vein thrombosis. Rare harms, such as osteonecrosis of the jaw and atypical femur fractures were not reported in this body of evidence but they may occur. The evidence is limited for subpopulations characterized by age, sex, baseline bone mineral density, and baseline fracture risk.

Abstract

Aim

To evaluate the impact of an aerobic fitness program on disease activity, defined by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and on C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and the Bath Ankylosing Spondylitis Functional Index (BASFI) in case of axial spondyloarthritis.

Methods

A systematic review of the literature, following the Prisma recommendations, was performed by two reviewers on the PubMed and Embase databases. Controlled trials assessing the efficacy of aerobic exercises compared to physiotherapy on axial spondyloarthritis disease activity were included. The diagnosis of axial spondyloarthritis was meeting the New York criteria and/or the Assessment in Axial Spondyloarthritis International Working Group criteria. Aerobic fitness was defined as an exercise performed at 50%-90% of the maximal heart rate or between 50% and 80% oxygen consumption (VO2 ) peak.

Results

Five hundred and twenty abstracts were identified and 93 abstracts were analyzed. Eight studies met the selection criteria and 6 were finally included in this study because of the presence of a control group. Both groups were similar in terms of age, sex ratio, disease duration. Aerobic exercise provided a positive impact on the BASDAI in the intervention group (148 patients) (weighted mean difference [WMD]: -0.52 [95% CI: -0.9 to -0.13]) (I2 : 10.3%, P = 0.35). However, when compared to a control group (152 patients), the improvement of BASDAI didn’t reach significance (WMD: -0.25 [95% CI: -0.83 to 0.32]) (I2 : 0%, P = 0.41). Aerobic exercise did not improve BASFI, CRP or ESR.

Conclusion

Aerobic exercise did not provide beneficial effects either on disease activity or on physical function and biological parameters when compared to a control group in axial spondyloarthritis.

Abstract

Objective
To assess the performance of various sonographic elemental entheseal lesions in distinguishing between psoriatic arthritis (PsA) and controls to inform the development of a novel sonographic enthesitis score for PsA.

Methods
A total of 100 age- and sex-matched individuals (50 PsA and 50 controls) were evaluated. Eleven entheseal sites were scanned bilaterally according to a standardized protocol by 2 sonographers. Based on the Outcome Measures in Rheumatology (OMERACT) definition of sonographic enthesitis, the following lesions were assessed: structural entheseal changes (hypoechogenicity), thickening, bone erosion, enthesophytes, calcification, and Doppler signal, in addition to bursitis and bone irregularities. The images were read by 2 readers blinded to the clinical information. A series of logistic regression models were used to find the optimal combination of entheseal sites and elementary lesions that distinguished PsA from controls.

Results
Mean age was 55 ± 10 years (59% males). The optimal model that distinguished PsA from controls included 5 elementary lesions (enthesophytes, Doppler signal, erosions, thickening, and hypoechogenicity) and 6 entheseal sites (patellar ligament insertions into the distal patella and tibial tuberosity, Achilles tendon and plantar fascia insertions into the calcaneus, common extensor tendon insertion into lateral epicondyle, and supraspinatus insertion into the superior facet of the humerus). The area under the receiver-operating characteristic curve for this model was 0.93 (95% CI 0.88–0.98).

Conclusion
We identified potential elemental ultrasonographic abnormalities and entheseal sites that could distinguish PsA and controls. This information will contribute to the development of a new sonographic score for assessment of enthesitis in patients with PsA.

Abstract

Guidance is provided in a European setting on the assessment and treatment of postmenopausal women at risk from fractures due to osteoporosis.

Introduction

The International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis published guidance for the diagnosis and management of osteoporosis in 2013. This manuscript updates these in a European setting.

Methods

Systematic reviews were updated.

Results

The following areas are reviewed: the role of bone mineral density measurement for the diagnosis of osteoporosis and assessment of fracture risk; general and pharmacological management of osteoporosis; monitoring of treatment; assessment of fracture risk; case-finding strategies; investigation of patients; health economics of treatment. The update includes new information on the evaluation of bone microstructure evaluation in facture risk assessment, the role of FRAX® and Fracture Liaison Services in secondary fracture prevention, long-term effects on fracture risk of dietary intakes, and increased fracture risk on stopping drug treatment.

Conclusion

A platform is provided on which specific guidelines can be developed for national use.

Highlights

• Secukinumab is effective for Behçet’s mucocutaneous and articular manifestations.

• Secukinumab 300 mg is superior to 150 mg for inducing articular and complete response.

• Due to secukinumab safety concerns in IBD, attention must be paid in entero-Behçet.

Abstract

Objective
To evaluate the efficacy and safety of secukinumab in Behçet’s patients with active mucocutaneous and articular manifestations refractory to previous treatments.

Methods
We retrospectively evaluated 5 patients treated with the IL17-inhibitor secukinumab and diagnosed with Behçet according to ISG/ICBD criteria. All patients had active mucocutaneous and articular manifestations refractory to colchicine, conventional DMARDs and at least one anti-TNFα agent. Four patients received secukinumab in the dose of 150 mg/monthly since also fulfilling the criteria for ankylosing spondylitis, while the fifth patient received secukinumab 300 mg/monthly because she met psoriatic arthritis criteria. Achievement of response was based on the number of oral ulcers, BASDAI and ASDAS for articular involvement, and BDCAF for Behçet activity. Complete response was defined as: i) decrease ≥50% in the number of oral ulcers; ii) BASDAI index <4; iii) ASDAS index <1.4; iv) decrease of 50% or more in BDCAF index.

Results
The patient starting secukinumab 300 mg/month successfully achieved complete response within 3 months. Complete response was maintained during all 9-months follow-up. Among the 4 subjects starting secukinumab 150 mg/month, two achieved complete response at month 6, but one relapsed. This patient and the two who not achieved complete response at month 6 were switched to secukinumab 300 mg/month. Within 3 months from the dosage increase, all three subjects successfully (re)achieved complete response.

Conclusion
Our study suggested for the first time that secukinumab (either 150 mg and 300 mg/month) improved active mucocutaneous manifestations refractory to previous treatments, while secukinumab 300 mg/monthly resulted superior in inducing articular and complete response in Behçet’s patients.