Raj Sengupta

Assessment of the impact of flares in ankylosing spondylitis disease activity using the Flare Illustration

OBJECTIVES Many AS patients report periods of perceived higher disease activity (flares). This pilot study aims to document disease activity patterns reported by AS patients and examine associations with disease-specific health status measures. METHODS Consecutive AS patients (n = 114) were asked whether they experience flares, and if they experience symptoms of AS between flares. They were shown the Flare Illustration of disease patterns over time and asked to select the pattern that best described their disease (i) since symptom onset and (ii) in the past year. Associations between reported disease pattern and disease activity (Bath AS Disease Activity Index, BASDAI); functional impairment (Bath AS Functional Index, BASFI); AS Quality of Life (ASQoL); Back Pain (Nocturnal and Overall) and demographic features were assessed in a subsample (n = 83) (statistical significance defined at P <or= 0.05). RESULTS Since disease onset 108/113 patients (96%) reported flares, and 82/99 (83%) reported symptoms of AS between flares. Flares typically lasted days or weeks. When patients were asked to characterize their disease pattern using the Flare Illustration, patterns with constant symptoms predominated (>70% of patients) and patterns with constant symptoms since onset (vs intermittent symptoms) were associated with worse health status (ASQoL: P = 0.007; BASDAI: P = 0.029; BASFI: P = 0.013, overall back pain: P = 0.025). CONCLUSIONS Almost all AS patients report flares in disease activity: 70-80% report constant symptoms with single/repeated flares, while 20-30% report flares with no intermittent symptoms. The former is associated with a significantly poorer health status. These findings will be validated in a prospective study.

The assessment of ankylosing spondylitis in clinical practice.

Ankylosing Spondylitis (AS) is a chronic inflammatory arthritis that predominantly affects the axial skeleton in adolescent patients causing spinal pain and stiffness. There is a marked delay, on average 8 years, between onset of disease symptoms and clinical diagnosis. The distinction between the symptoms of mechanical and inflammatory back pain remains one of the main contributing factors for the delay in diagnosis. Several classification criteria exist to aid the diagnosis of AS, but their accuracy is poor. The Ankylosing Spondylitis Assessment Study group (ASAS) has defined a core set of domains for clinical outcome measurement in AS in order to assess the disease process in individual patients and to identify those with rapidly progressive disease. New therapies, such as the tumor necrosis factor (TNF) inhibitors, have transformed the treatment paradigm in AS, especially for those patients with aggressive disease. Thus, the definition of both patient selection criteria for these agents and the development of clinical methods to assess response to therapy have become a priority. This Review focuses on measuring the degree of disease activity, function and damage in patients with AS in an ambulatory care setting, and the assessment of suitability of various outcome measures for monitoring response to treatment with TNF inhibitors.

Exploring ankylosing spondylitis-associated ERAP1, IL23R and IL12B gene polymorphisms in subphenotypes of psoriatic arthritis

OBJECTIVE To ascertain whether AS-associated polymorphisms of ERAP1, IL23R and IL12B genes associate with subphenotypes of PsA, particularly axial radiographic disease once stratified by HLA-B27 and HLA-Cw*0602 status. METHODS rs30187 (ERAP1 gene), rs6887695 (IL12B gene), rs11209026 and rs7530511 (IL23R gene) single nucleotide polymorphisms were genotyped in 263 PsA cases from a prospective cohort and compared with data from healthy controls (n = 3266-5422). ERAP1 results were stratified according to HLA-B27 and HLA-Cw*0602 status. Investigation of association with age at onset of psoriasis/PsA, arthritic joint count, axial radiographic disease, peripheral radiographic erosions, Psoriasis Area Severity Index, nail score and HAQ was made. RESULTS There was a strong association between rs6887595 (IL12B) and PsA, with homozygosity for the major allele being more frequent in PsA than controls (odds ratio 1.70; 95% CI 1.3, 2.2; P < 0.001). A trend was demonstrated for the minor allele of rs11209026 (IL23R) to be less frequent in patients with erosive joint disease than in those without erosions or controls (7%, 14% and 12%, respectively). None of the polymorphisms associated with the presence of axial radiographic disease or other clinical parameters. CONCLUSION We have confirmed a strong association between rs6887595 (IL12B) and PsA. A trend has been demonstrated between an IL23R variant and peripheral erosive disease. ERAP1 was not associated with axial radiographic disease in PsA. Spinal involvement in PsA may be genetically different from that in AS, which is in keeping with previous observations that the clinical and radiographic pattern of axial disease also differs.

Serum Soluble Bone Turnover Biomarkers in Psoriatic Arthritis and Psoriatic Spondyloarthropathy

Because psoriatic arthritis (PsA) is an inflammatory disease of joints, serum soluble biomarkers specific for chronic joint and bone inflammation may predict future disease severity and response to therapy, thereby informing stratified medicine approaches. The objectives of our systematic review were to determine whether serum soluble bone and cartilage turnover biomarkers are (1) associated with PsA or psoriatic spondyloarthropathy; and (2) associated with disease activity, disease severity, or clinical phenotype. Ten studies met eligibility criteria. Matrix metalloproteinase (MMP)-3, Dickkopf (DKK)-1, macrophage colony-stimulating factor (M-CSF), crosslinked telopeptide of collagen-1, and tumor necrosis factor-related apoptosis-inducing ligand were associated with PsA, with equivocal results for osteoprotegerin (OPG) and bone alkaline phosphatase (ALP). MMP-3, DKK-1, M-CSF, CPII:C2C (ratio of cartilage degradation vs byproduct formation), and possibly OPG were associated with PsA independently of psoriasis. C1-2C (a neoepitope released when type 2 cartilage is degraded by collagenases) was associated with both tender and swollen joint counts, and bone morphogenetic protein-4 with patient global assessment of disease, pain score, and the Bath Ankylosing Spondylitis Disease Activity Index. Bone ALP was associated with disease activity. M-CSF and receptor activator of nuclear factor-κB ligand were associated with several plain radiographic features. No studies have investigated biomarker associations specifically with axial PsA.

Axial Disease in Psoriatic Arthritis study: defining the clinical and radiographic phenotype of psoriatic spondyloarthritis

Objectives To compare the prevalence, clinical and radiographic characteristics of psoriatic spondyloarthritis (PsSpA) in psoriatic arthritis (PsA), with ankylosing spondylitis (AS). Methods A prospective single-centre cross-sectional observational study recruited consecutive PsA and AS cases. Participants completed outcome measures, and underwent clinical examination, axial radiographic scoring and HLA-sequencing. Multivariable analyses are presented. Results The 402 enrolled cases (201 PsA, 201 AS; fulfilling classification criteria for respective conditions) were reclassified based upon radiographic axial disease and psoriasis, as: 118 PsSpA, 127 peripheral-only PsA (pPsA), and 157 AS without psoriasis (AS) cases. A significant proportion of patients with radiographic axial disease had PsSpA (118/275; 42.91%), and often had symptomatically silent axial disease (30/118; 25.42%). Modified New York criteria for AS were fulfilled by 48/201 (23.88%) PsA cases, and Classification of Psoriatic Arthritis criteria by 49/201 (24.38%) AS cases. pPsA compared with PsSpA cases had a lower frequency of HLA-B*27 (OR 0.12; 95% CI 0.05 to 0.25). Disease activity, metrology and disability were comparable in PsSpA and AS. A significant proportion of PsSpA cases had spondylitis without sacroiliitis (39/118; 33.05%); they less frequently carried HLA-B*27 (OR 0.11; 95% CI 0.04 to 0.33). Sacroiliac joint complete ankylosis (adjusted OR, ORadj 2.96; 95% CI 1.42 to 6.15) and bridging syndesmophytes (ORadj 2.78; 95% CI 1.49 to 5.18) were more likely in AS than PsSpA. Radiographic axial disease was more severe in AS than PsSpA (Psoriatic Arthritis Spondylitis Radiology Index Score: adjusted incidence risk ratio 1.13; 95% CI 1.09 to 1.19). Conclusions In a combined cohort of patients with either PsA or AS from a single centre, 24% fulfilled classification criteria for both conditions. The pattern of axial disease was influenced significantly by the presence of skin psoriasis and HLA-B*27.

Juvenile versus adult-onset ankylosing spondylitis -- clinical, radiographic, and social outcomes. a systematic review.

Ankylosing spondylitis (AS) has 2 main modes of onset: juvenile-onset AS (JoAS) and adult-onset AS (AoAS). It is not known whether JoAS is a subtype of AS, or AS modulated by early age of onset and longer disease duration. We performed a systematic review of the literature, identifying 12 articles and 1 abstract directly comparing JoAS and AoAS cohorts, with observational study design. Patients with JoAS appear to have more peripheral joint involvement both clinically and radiographically (especially knees and ankles) and more root joint involvement (hips and shoulders); they are more likely to proceed to hip arthroplasty and often initially present with peripheral rather than axial symptoms. Patients with AoAS appear to have more axial symptoms and radiographic disease, particularly in the lumbar spine, and worse axial metrology. In terms of other characteristics, more evidence is needed to confidently state whether JoAS and AoAS are different.

Clinical outcomes and progression to orthopedic surgery in juvenile versus adult-onset ankylosing spondylitis

Juvenile‐ and adult‐onset ankylosing spondylitis (AS) are subtypes of AS that may have different clinical outcomes. We compared cohorts of juvenile‐onset AS and adult‐onset AS in terms of clinical characteristics, clinical outcomes, proceeding to AS‐related orthopedic surgery, and type of orthopedic surgery.

Feasibility, reliability, and sensitivity to change of four radiographic scoring methods in patients with psoriatic arthritis

We set out to assess the feasibility, reliability, and sensitivity to change of 4 radiographic scoring methods in psoriatic arthritis (PsA).

Prevalence and factors associated with disturbed sleep in patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis: a systematic review

This review explores the prevalence and factors associated with disturbed sleep for patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis in order to clarify consistent findings in this otherwise disparate research field. The association of physical, demographic and psychological factors correlating with poor sleep was explored, and the effectiveness of interventions assessed. Ten electronic databases were searched: AMED, CINAHL, Embase, Medline, PsycINFO, PubMed, Scopus, Web of Science, OpenGrey and BASE. Following application of inclusion and exclusion criteria, 29 articles were critically assessed on the basis of methodology, experimental design, ethics and quality of sleep data, leading to the selection of 15 studies for final review. Poor sleep was reported in 35–90% of patients with axial spondyloarthritis and is more prevalent within this clinical population compared to healthy control subjects. Disturbed sleep is an important aspect of disease for patients and reflects the severity of disease activity, pain, fatigue and functional disability. However, the direction of this relationship is undetermined. Associations with age, gender, years spent in education, quality of life and depression have also been demonstrated. Anti-TNF medication is effective in reducing poor sleep, and exercise has also produced beneficial results. Future research into poor sleep should take account of its multifactorial nature. There is also a current lack of research investigating non-pharmacological interventions or combination therapies. A standardised, validated measurement of poor sleep, appropriate for regular patient screening, would be a useful first step for future research.

BSR and BHPR guideline for the treatment of axial spondyloarthritis (including ankylosing spondylitis) with biologics

Axial SpA (axSpA) is a chronic inflammatory condition predominantly involving the spine and sacroiliac joints (SIJ), with or without extra-spinal manifestations including peripheral arthritis, enthesitis, iritis, psoriasis and IBD. Individuals with axSpA experience significant pain, stiffness and lack of function, which translates into important health care costs and increased mortality. AxSpA can be classified into two subgroups: radiographic axSpA, commonly referred to as AS, and non-radiographic axSpA (nr-axSpA). The primary difference between these two subgroups is the presence or absence of defined structural changes in the SIJ as detected on plain radiography. A diagnosis of AS can be made according to the modified New York criteria when radiographs show at least grade 2 sacroiliitis bilaterally or grade 3 unilaterally, in the presence of appropriate clinical symptoms [1]. In contrast, SIJ radiographs may be completely normal in nr-axSpA. The radiographic changes of AS may take 8 10 years to manifest, with a progression rate from nr-axSpA to AS of 12% every 2 years [2], although some patients with nr-axSpA never develop AS. Disease progression is predicted most strongly