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ObjectiveEnthesitis is a key pathological and clinical feature of psoriatic arthritis (PsA) in children and adults. Enthesitis is typically assessed clinically using several validated enthesitis scoring systems that have been used in clinical trials. Enthesitis treatment response has been reported as change in the total enthesitis score or the proportion of patients who achieved complete resolution. The majority of trials in PsA did not require patients to have enthesitis at study entry since enthesitis was evaluated only as a secondary outcome. Despite the inherent limitations of the clinical assessment of enthesitis, imaging of the entheses using ultrasound or magnetic resonance imaging has rarely been used in clinical trials to assess response to treatment of enthesitis. This systematic review summarizes existing evidence regarding pharmaceutical and nonpharmaceutical interventions for enthesitis in patients with PsA to facilitate an evidence-based update of the Group for Research and Assessment in Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations for PsA.MethodsWe performed a systematic literature review to identify 41 randomized clinical trials that reported enthesitis treatment response in patients with PsA. For each intervention, the response effect size was summarized and the quality of evidence was graded. Recommendations were then formulated for the various pharmacological and nonpharmacological therapies.ResultsWe included 41 randomized clinical trials in our review and graded each intervention.ConclusionSeveral classes of systemic conventional and advanced therapies and local measures were recommended for active enthesitis in patients with PsA.

Objective.To reach a consensus on the instruments to be used in clinical practice to evaluate the effectiveness of biological disease-modifying antirheumatic drug (bDMARD) treatment in patients with psoriatic arthritis (PsA) in the short to medium term (3–6 mos), and to establish the minimum health outcomes for treatment continuation.Methods.A 2-round Delphi questionnaire was developed based on both the information gathered in the literature review and 4 discussion groups. The suitability and feasibility of the proposed sets of instruments were assessed on a 7-point Likert scale. Consensus was established when at least 75% of healthcare professionals (HCP) reached agreement. To define a minimum health outcome to continue treatment, a combination of 4 disease activity states and 3 health-related quality of life states were defined for 3 hypothetical patient profiles. HCP were given a dichotomous choice (yes/no) to respond to whether they would continue treatment in each case.Results.The second round was completed by 106 HCP. Consensus was reached on the use of (1) Disease Activity in Psoriatic Arthritis + Psoriatic Arthritis Impact of Disease (PsAID12) or minimal disease activity + PsAID12 + C-reactive protein, in peripheral PsA; and (2) Ankylosing Spondylitis Disease Activity Score + PsAID12, in axial PsA. Health outcomes considered sufficient to continue treatment were stricter for bDMARD-naive patients than for patients who failed several bDMARD.Conclusion.To the best of our knowledge, this is the first multidisciplinary consensus on a set of outcomes for the evaluation of bDMARD effectiveness in PsA, in routine clinical practice.

Objective.To examine the grade of agreement between very low disease activity (VLDA) and Disease Activity Index for Psoriatic Arthritis (DAPSA) remission, as well as their association with the effect of the disease as assessed by the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire in patients with psoriatic arthritis in routine clinical practice.Methods.Posthoc analysis of data from a cross-sectional multicenter study. Patients were included who fulfilled the Classification for Psoriatic Arthritis (CASPAR) criteria with at least 1 year of disease duration and were treated with biological and/or conventional synthetic disease-modifying antirheumatic drugs according to routine clinical practice in Spain. Patients were considered in VLDA if they met 7/7 of the minimal disease activity criteria. DAPSA and clinical (c)DAPSA score ≤ 4 identified remissions.Results.Of the 227 patients included in the original study, 26 (11.5%), 52 (22.9%), and 65 (28.6%) were in VLDA, DAPSA remission, and cDAPSA remission, respectively. There was a moderate agreement between VLDA and DAPSA remission (κ = 0.52) or cDAPSA remission (κ = 0.42). Patients with VLDA had less effect of the disease as measured by PsAID [mean total score (SD): VLDA 1.1 (1.2); DAPSA remission 1.3 (1.5); cDAPSA remission 1.7 (1.6)]. There was a moderate agreement between DAPSA remission or cDAPSA remission and PsAID < 4 (κ = 0.46 and κ = 0.58 respectively), while poor agreement (κ = 0.18) was found between VLDA and PsAID < 4.Conclusion.VLDA criteria seem to be more stringent for assessing a status of remission; however, DAPSA remission shows better correlation with a patient-acceptable symptoms state than VLDA does.

Objective.To study the qualitative and quantitative phenotypic changes that occur in molecules involved in antigen presentation and costimulation in synovial B cells from rheumatoid arthritis (RA) and psoriatic arthritis (PsA).Methods.The presence of HLA-DR, CD86, and CD40 in CD20+ cells was studied in RA synovium biopsies using immunohistochemistry and immunofluorescence. Expression was assessed by flow cytometry of the Class II molecules CD40, CD86, CD23, and CD27 on B cells from the synovial fluid (SF), with respect to peripheral blood, from 13 patients with RA and 15 patients with PsA. Expression of interferon-induced protein with tetratricopeptide repeats 4 (IFIT4) in immune-selected CD20+ cells from patients with RA was assessed by quantitative realtime PCR.Results.Infiltrating synovial RA, B cells expressed HLA-DR, CD40, and CD86. Increased expression of CD86, HLA-DR, and HLA-DQ in B cells from SF was found in patients with RA and PsA. HLA-DP was also elevated in rheumatoid SF B cells; conversely, a significantly lower expression was observed in SF from patients with PsA. CD40 expression was increased in SF B cells from PsA, but not in patients with RA. Interestingly, CD20 surface expression level was significantly lower in SF B cells (CD19+, CD138−) from RA, but not in patients with PsA. CD27 upregulation and CD23 downregulation were observed in synovial B cells in both pathologies. Finally, a 4-fold increase in IFIT4 mRNA content was shown in B cells from SF in patients with RA.Conclusion.Synovial B cells from patients with RA and patients with PsA express different antigen-presenting cell phenotypes, suggesting that this cell type plays a dissimilar role in the pathogenesis of each disease.

Objective.To investigate the presence of subclinical synovitis by ultrasound (US) and the clinical phenotype in patients with palindromic rheumatism (PR) according to anticitrullinated protein antibody (ACPA) status.Methods.Fifty-four patients with PR were studied. Clinical, demographic, serological, and therapeutic characteristics were compared in ACPA-positive and ACPA-negative patients. US searching for synovial hypertrophy (SH) and power Doppler signal (PDUS) in 22 joints of the hands was performed in the intercritical period. The results were compared according to ACPA status and with a healthy control group (n = 30). In 10 patients, US was performed during the joint attack.Results.Most patients were female (63%) with a mean disease duration of 11.6 ± 10.7 years. Thirty-six patients (66.7%) were ACPA-positive. ACPA-positive patients had a shorter duration of attacks, a younger age, and less knee involvement at disease onset. US examination showed SH grade ≥ 1 in 79.6% of patients with PR and 50% of controls. Significant US results (SH ≥ 2 or PDUS) were observed in 2.7% and 1.4% of joints assessed and in 33% and 25.9% of patients with PR, respectively. Only 4 patients (7.4%) had US active synovitis (SH ≥ 2 plus PDUS) in at least 1 joint. US assessment showed no significant differences between ACPA-positive and ACPA-negative patients. PDUS was observed in 7 out of 10 patients during attacks.Conclusion.Some differences emerged in the clinical phenotype of PR according to ACPA status. Most patients with PR do not have US subclinical synovitis in the intercritical period, even those who are ACPA-positive.

Objective.To evaluate clinical factors associated with the absence of radiographic progression in patients with spondylitis.Methods.The cross-sectional study included 672 patients. All patients presented a disease evolution of more than 15 years. Patients were classified as with radiographic spinal involvement versus without radiographic spinal involvement. We included clinical variables potentially related to null radiological progression.Results.Seventy-five patients had no radiographic involvement. These patients were predominantly female, had a lower erythrocyte sedimentation rate (ESR), and a lower C-reactive protein level. Multivariate analysis showed an association with the female sex and low ESR.Conclusion.Clinical factors associated with this lack of progression were female sex and low ESR.

Objective.To analyze longterm progression to rheumatoid arthritis (RA) and the predictive value of anticitrullinated peptide/protein antibodies (ACPA) in palindromic rheumatism (PR).Methods.We selected all patients in our clinic with PR who had at least 1 ACPA measurement. We included only patients with pure PR, defined as no evidence of associated rheumatic disease at the first serum ACPA measurement. Clinical characteristics, serum ACPA levels, duration of PR until serum ACPA measurement, and total followup time were recorded. The outcome variable was the definitive diagnosis of RA. The prognostic value of ACPA status in pure PR for a definite diagnosis of RA was analyzed by different statistical methods.Results.Seventy-one patients (54 women/17 men) with a PR diagnosis were included. Serum ACPA were positive in 52.1%. After a mean followup of 7.6 ± 4.7 years since the first ACPA measurement, 24 patients (33.8%) progressed to chronic disease: 22% RA, 5.6% systemic lupus erythematosus, and 5.6% other diseases. The positive likelihood ratio of ACPA status for RA was 1.45, and the area under the receiver-operating characteristic curve of ACPA titers was 0.60 (95% CI 0.45−0.75). Progression to RA was more frequently seen in ACPA-positive than in ACPA-negative patients (29.7% vs 14.7%), but the difference was not significant (hazard ratio 2.46, 95% CI 0.77−7.86). Mean ACPA levels of patients with pure PR did not differ significantly from those of patients who progressed to RA.Conclusion.ACPA are frequently found in the sera of patients with PR, and a significant proportion of these patients do not progress to RA in the long term.

OBJECTIVE: The efficacy of antibody-based biological therapies currently used in psoriatic arthritis (PsA) depends not only on their blocking effect on the targeted molecule but also on their binding affinity to genetically defined variants of cell-surface Fc-γ receptors. Our objective was to assess the potential influence of functionally relevant FCGR2A/CD32A (H131R) and FCGR3A/CD16A (V158F) genetic polymorphisms on the EULAR response to tumor necrosis factor-α (TNF-α) blocker therapy in PsA. METHODS: In total 103 patients with PsA starting anti-TNF-α therapy were included. The efficacy of therapy was evaluated according to EULAR response criteria at 3 and 6 months. FCGR2A-R131H and FCGR3A-F158V polymorphisms were genotyped. Potential correlations between clinical response and the FCGR2A-R131H and FCGR3A-F158V polymorphisms were evaluated. RESULTS: EULAR response (moderate plus good) was 85.4% at 3 months and 87.4% at 6 months, while good EULAR response was 61.2% and 62.1%, respectively. More patients with high-affinity FCGR2A genotypes (homozygous or heterozygous combinations) achieved a EULAR response at 6 months compared to patients with the low-affinity genotype (RR; p = 0.034, adjusted comparison error rate < 0.025). This association was due mainly to the group of patients treated with etanercept. No correlation was found for the FCGR3A polymorphism. Similarly, no effect of C-reactive protein levels was observed. CONCLUSION: Our data indicate that FCGR2A polymorphism may influence the response to TNF-α blockers (namely etanercept) in PsA in a direction opposite to that previously found in patients with rheumatoid arthritis.

OBJECTIVE: To analyze the effects of cigarette smoking on disease activity and radiographic damage in patients with early rheumatoid arthritis (RA). METHODS: Study subjects were 156 patients with early RA (< 2 yrs). Disease activity, therapeutic response, and radiographic progression were compared in smokers and nonsmokers at 24 months. RESULTS: At baseline, ever-smokers had earlier disease onset and a closer association with the shared epitope (SE), but not more seropositive disease. No significant differences were observed in disease activity and European League Against Rheumatism therapeutic responses between smokers and nonsmokers. Multivariate analysis showed that baseline Larsen score, the HLA-DRB*04 genotype, being female, and current smoking were associated with radiographic progression. CONCLUSION: In patients with early RA, smoking was associated with earlier disease onset and the SE. Smoking was an independent factor of radiographic progression.