Philip S. Helliwell

Treating spondyloarthritis, including ankylosing spondylitis and psoriatic arthritis, to target: recommendations of an international task force

Background Therapeutic targets have been defined for diseases like diabetes, hypertension or rheumatoid arthritis and adhering to them has improved outcomes. Such targets are just emerging for spondyloarthritis (SpA). Objective To define the treatment target for SpA including ankylosing spondylitis and psoriatic arthritis (PsA) and develop recommendations for achieving the target, including a treat-to-target management strategy. Methods Based on results of a systematic literature review and expert opinion, a task force of expert physicians and patients developed recommendations which were broadly discussed and voted upon in a Delphi-like process. Level of evidence, grade and strength of the recommendations were derived by respective means. The commonalities between axial SpA, peripheral SpA and PsA were discussed in detail. Results Although the literature review did not reveal trials comparing a treat-to-target approach with another or no strategy, it provided indirect evidence regarding an optimised approach to therapy that facilitated the development of recommendations. The group agreed on 5 overarching principles and 11 recommendations; 9 of these recommendations related commonly to the whole spectrum of SpA and PsA, and only 2 were designed separately for axial SpA, peripheral SpA and PsA. The main treatment target, which should be based on a shared decision with the patient, was defined as remission, with the alternative target of low disease activity. Follow-up examinations at regular intervals that depend on the patients status should safeguard the evolution of disease activity towards the targeted goal. Additional recommendations relate to extra-articular and extramusculoskeletal aspects and other important factors, such as comorbidity. While the level of evidence was generally quite low, the mean strength of recommendation was 9–10 (10: maximum agreement) for all recommendations. A research agenda was formulated. Conclusions The task force defined the treatment target as remission or, alternatively, low disease activity, being aware that the evidence base is not strong and needs to be expanded by future research. These recommendations can inform the various stakeholders about expert opinion that aims for reaching optimal outcomes of SpA.

Defining minimal disease activity in psoriatic arthritis: a proposed objective target for treatment

Objective: To create minimal disease activity (MDA) criteria for psoriatic arthritis (PsA). With recent therapeutic advances, this is now a goal for treatment and may represent a measure to compare therapies. It defines a satisfactory state of disease activity rather than a change, and encompasses all aspects of the disease. Methods: 40 patient profiles were sampled from an observational PsA database. Sixty experts in PsA classified these as in MDA or not. A consensus of ⩾70% was accepted, identifying 13 profiles in MDA. Summary statistics created possible cut-off points for the definition. Considering the number of measures that must be met, 35 candidate definitions were created and tested using receiver operating characteristic curves (ROC) for sensitivity and specificity. Results: Four candidate definitions showed high area under the curve values on ROC testing. Definitions with high outlying values were excluded as they were not considered to represent MDA. Aiming for high specificity to reduce false positives resulted in a preference for the following definition: “A patient is classified as achieving MDA when meeting 5 of the 7 following criteria: tender joint count ⩽1; swollen joint count ⩽1; Psoriasis Activity and Severity Index ⩽1 or body surface area ⩽3; patient pain visual analogue score (VAS) ⩽15; patient global disease activity VAS ⩽20; health assessment questionnaire ⩽0.5; tender entheseal points ⩽1”. Conclusion: This study provides the first definition of a “state” of MDA in PsA and defines a target for treatment. It must now be validated in other populations and tested in clinical trials.

The Prevalence of Psoriatic Arthritis in People With Psoriasis

OBJECTIVEnTo determine the prevalence of psoriatic arthritis (PsA) using the ClASsification criteria for Psoriatic ARthritis (CASPAR) for classification.nnnMETHODSnPeople with psoriasis were identified from the computerized morbidity indices of 2 large UK general practices, total population 22,500. Questionnaires were mailed to all 633 patients thus identified. Of the respondents, a 50% sample was assessed clinically and a proportion had blood samples and radiographs taken. Patients labeled as having psoriasis were also cross-referenced with a local secondary care morbidity index for PsA and rheumatoid arthritis. Figures for the prevalence of PsA were estimated from these data.nnnRESULTSnOne hundred sixty-eight questionnaires were returned (response rate 27%) and 93 people (55% of questionnaire respondents) were examined. Of these 93 people, 12 (4 of whom were cross-referenced to the hospital database) were thought to have PsA clinically, all fulfilling the CASPAR criteria for PsA. Six of the 93 examined patients did not have psoriasis or a family history of psoriasis and had no historical features or clinical signs of psoriasis on interview and examination. Extrapolating from the data of those people actually examined, the estimated (corrected) prevalence was 13.8% (95% confidence interval 7.1-24.1%).nnnCONCLUSIONnThe estimated prevalence of PsA in this population, using the CASPAR criteria, was 13.8%. Misclassification of psoriasis and arthritis, and response bias, indicate that this is probably an overestimate.

Validation of Minimal Disease Activity Criteria for Psoriatic Arthritis Using Interventional Trial Data

New criteria for minimal disease activity (MDA) in psoriatic arthritis (PsA) have been developed. The aim is to provide further validation of these criteria using data obtained in interventional trials with infliximab, a drug with proven efficacy in PsA.

Is There Subclinical Synovitis in Early Psoriatic Arthritis? A Clinical Comparison With Gray‐Scale and Power Doppler Ultrasound

Arthritis activity assessments in psoriatic arthritis (PsA) have traditionally relied on tender and swollen joint counts, but in rheumatoid arthritis, multiple studies have demonstrated subclinical inflammation using modern imaging. The aim of this study was to compare clinical examination and ultrasound (US) findings in an early PsA cohort.

Phosphodiesterase 4 Inhibition in the Treatment of Psoriasis, Psoriatic Arthritis and Other Chronic Inflammatory Diseases

Agents which increase intracellular cyclic adenosine monophosphate (cAMP) may have an antagonistic effect on pro-inflammatory molecule production so that inhibitors of the cAMP degrading phosphodiesterases have been identified as promising drugs in chronic inflammatory disorders. Although many such inhibitors have been developed, their introduction in the clinic has been hampered by their narrow therapeutic window with side effects such as nausea and emesis occurring at sub-therapeutic levels. The latest generation of inhibitors selective for phosphodiesterase 4 (PDE4), such as apremilast and roflumilast, seems to have an improved therapeutic index. While roflumilast has been approved for the treatment of exacerbated chronic obstructive pulmonary disease (COPD), apremilast shows promising activity in dermatological and rheumatological conditions. Studies in psoriasis and psoriatic arthritis have demonstrated clinical activity of apremilast. Efficacy in psoriasis is probably equivalent to methotrexate but less than that of monoclonal antibody inhibitors of tumour necrosis factor (TNFi). Similarly, in psoriatic arthritis efficacy is less than that of TNF inhibitors. PDE4 inhibitors hold the promise to broaden the portfolio of anti-inflammatory therapeutic approaches in a range of chronic inflammatory diseases which may include granulomatous skin diseases, some subtypes of chronic eczema and probably cutaneous lupus erythematosus. In this review, the authors highlight the mode of action of PDE4 inhibitors on skin and joint inflammatory responses and discuss their future role in clinical practice. Current developments in the field including the development of topical applications and the development of PDE4 inhibitors which specifically target the subform PDE4B will be discussed.

Is there subclinical enthesitis in early psoriatic arthritis? A clinical comparison with power doppler ultrasound

Enthesitis is a recognized feature of spondylarthritides (SpA), including psoriatic arthritis (PsA). Previously, ultrasound imaging has highlighted the presence of subclinical enthesitis in established SpA, but there are little data on ultrasound findings in early PsA. The aim of our study was to compare ultrasound and clinical examination (CE) for the detection of entheseal abnormalities in an early PsA cohort.

Quantitative Magnetization Transfer Ultrashort Echo Time Imaging of the Achilles Tendon

Ultrashort echo time imaging allows the short T2 Achilles tendon to be directly visualized with MRI. Radiofrequency saturation 1 kHz or less off‐resonance has been used previously to improve image contrast. In this study, magnetization transfer was investigated in the Achilles tendon of eight normal volunteers and one patient with psoriatic arthritis. 2D Ultrashort echo time images were acquired using saturation pulses 2–100 kHz off‐resonance at 4 pulse powers. On‐resonance saturation recovery images were also obtained to estimate T1. The results were fitted to a two compartment quantitative magnetization transfer model. The estimated bound proton fraction for the eight healthy volunteers was 21.0 ± 1.2% (mean ± standard deviation) compared to 16.4% in the patient with psoriatic arthritis (P < 0.05). The T2 of the bound protons was measured as 6.1 ± 0.3 μsec in the healthy volunteers and 6.0 μsec in the patient. This technique appears clinically feasible and may be useful for assessing the collagen and water changes which occur in Achilles tendinopathy. Magn Reson Med, 2011.

Psoriasis, psoriatic arthritis, and rheumatoid arthritis: Is all inflammation the same?☆

OBJECTIVESnTo review the pathophysiology, co-morbidities, and therapeutic options for psoriasis, psoriatic arthritis and rheumatoid arthritis in order to further understand the similarities and differences in treatment paradigms in the management of each disease. New targets for individualized therapeutic decisions are also identified with the aim of improving therapeutic outcome and reducing toxicity.nnnSEARCH STRATEGYnUsing the PubMed database, we searched literature published from 2000 to 2015 using combinations of the key words psoriasis, psoriatic arthritis, rheumatoid arthritis, pathogenesis, immunomodulation, and treatment.nnnINCLUSION AND EXCLUSION CRITERIAnThis was a non-systematic review and there were no formal inclusion and exclusion criteria.nnnDATA EXTRACTIONnAbstracts identified in the search were screened for relevance and articles considered appropriate evaluated further. References within these selected articles were also screened. Information was extracted from 198 articles for inclusion in this report.nnnDATA SYNTHESISnThere was no formal data synthesis. Articles were reviewed and summarized according to disease area (psoriasis, psoriatic arthritis, and rheumatoid arthritis).nnnHEADLINE RESULTSnThe pathophysiology of psoriasis, psoriatic arthritis, and rheumatoid arthritis involves chronic inflammation mediated by pro-inflammatory cytokines. Dysfunction in integrated signaling pathways affecting different constituents of the immune system result in varying clinical features in the three diseases. Co-morbidities, including cardiovascular disease, malignancies, and non-alcoholic fatty liver disease are increased. Increased understanding of the immunopathogenesis allowed development of targeted treatments; however, despite a variety of potentially predictive genetic, protein and cellular biomarkers, there is still significant unmet need in these three inflammatory disorders.

Disease measurement – enthesitis, skin, nails, spine and dactylitis

Outcome measurement is a key part of study design but presents particular challenges in spondyloarthropathy. Enthesitis and dactylitis are typical features of spondyloarthropathy and validated scoring systems for both are available, although the majority of enthesitis outcome measures are validated in ankylosing spondylitis (AS) only. Assessment of axial disease is well researched in AS and composite outcome measures are routinely used. However, assessment of axial disease in predominantly peripheral arthritis, such as psoriatic arthritis, is problematic and under-researched. Extensive research in dermatology has provided multiple outcome measures for skin psoriasis. The psoriasis area and severity index (PASI) remains the most common outcome measure used, despite the fact that significant problems exist with this scale and that newer scoring methods and modifications of the PASI show better validity. Nail psoriasis is accurately measured by detailed scoring systems but these can be time-consuming.