Patient perception of treatment efficacy, disability and health satisfaction

Abstract published in Rheumatology, Volume 55 (Suppl 1), April 2016, page i123

Tailored treatment options for patients with psoriatic arthritis and psoriasis: review of established and new biologic and small molecule therapies

The diverse clinical picture of PsA suggests the need to identify suitable therapies to address the different combinations of clinical manifestations. This review aimed to classify the available biologic agents and new small molecule inhibitors (licensed and nonlicensed) based on their proven efficacy in treating different clinical manifestations associated with psoriasis and PsA. This review presents the level of evidence of efficacy of different biologic treatments and small molecule inhibitors for certain clinical features of treatment of PsA and psoriasis, which was graded in categories I–IV. The literature searches were performed on the following classes of biologic agents and small molecules: TNF inhibitors (adalimumab, etanercept, infliximab, golimumab, certolizumab), anti-IL12/IL23 (ustekinumab), anti-IL17 (secukinumab, brodalumab, ixekizumab), anti-IL6 (tocilizumab), T cell modulators (alefacept, efalizumab, abatacept, itolizumab), B cell depletion therapy (rituximab), phosphodiesterase 4 inhibitor (apremilast) and Janus kinase inhibitor (tofacitinib). A comprehensive table including 17 different biologic agents and small molecule inhibitors previously tested in psoriasis and PsA was generated, including the level of evidence of their efficacy for each of the clinical features included in our review (axial and peripheral arthritis, enthesitis, dactylitis, and nail and skin disease). We also proposed a limited set of recommendations for a sequential biologic treatment algorithm for patients with PsA who failed the first anti-TNF therapy, based on the available literature data. There is good evidence that many of the biologic treatments initially tested in psoriasis are also effective in PsA. Further research into both prognostic biomarkers and patient stratification is required to allow clinicians the possibility to make better use of the various biologic treatment options available. This review showed that there are many potentially new treatments that are not included in the current guidelines that can be used for selected categories of patients based on their disease phenotype, clinician experience and access to new biologic therapies

Differential peripheral B cell phenotype in patients with primary Sjögren’s syndrome (pSS) compared to secondary Sjögren’s syndrome associated with systemic lupus erythematosus (SS/SLE)

Introduction: Peripheral B-cell abnormalities, a feature of both systemic lupus erythematosus (SLE) and primary Sjogren’s syndrome (pSS), are implicated in the pathogenesis of both diseases and correlate with disease activity. This study aims to investigate how the defective B-cell phenotype in pSS patients compares to patients with SS and SLE (SS/SLE), and whether abnormalities in B-cell phenotype could be related to differential B-cell lipid-raft expression and B-cell activating factor (BAFF) receptor function in patients with pSS and SLE and secondary SS (SS/SLE). Methods: Blood samples and clinical and laboratory parameters from 32 patients with pSS and SS/SLE and 13 age/sex matched HC were obtained. We used flow-cytometry to perform B-cell immunophenotyping and analysed lipid-raft expression (marker of B-cell activation). In vitro cultures were also used to assess lipid-raft expression in response to BAFF. Results: Patients with SS/SLE had a significantly decreased Bm1 and Bm5 and increased Bm2 populations compared to HC (p=0.031, p=0.035 and p=0.01, respectively), and increased Bm2 compared to pSS (p=0.027). Bm1-cells were decreased in both pSS and SS/SLE patients compared to HC (p=0.028 and p= 0.031, respectively). Both age and disease duration correlated strongly with Bm2’ cells in SS/SLE patients (r=0.9572, p= 0.0428), and the immunosuppressive treatment correlated negatively with the number of circulating Bm2 and Bm2’ cell in pSS (r = -0.54, p=0.01 and r = -0.56, p=0.008, respectively). B-cells from patients with pSS had a significant increase in lipid-raft expression compared to HC (p=0.01) and patients with SS/SLE (p<0.05). Lipid-raft levels correlated with BAFF-receptor expression in HC and SS/SLE B-cells (p=0.17, r=0.694) but not in pSS patients. Both disease activity score (ESSDAI) and IgG level correlated positively with lipid rafts expression in B cells from patients with pSS (r = 0.79, p=0.004 and r =0.53, p=0.04, respectively). Conclusion: Patients with SS/SLE had more significant B-cell abnormalities compared to HC and pSS, detectable even in a small number of patients. Also the relationship between lipid-raft and BAFF-receptor expression was altered between pSS and SS/SLE patients, and correlated with the disease activity and IgG levels in pSS group, suggesting that therapies targeting BAFF might be particularly successful in the SS/SLE sub-group of patients

A systematic review of primary Sjögren’s syndrome in male and paediatric populations

Primary Sjögren’s syndrome (pSS) is a chronic multisystem autoimmune rheumatic disease characterised by female predominance. Although the disease is rare in the male and paediatric populations, it has been suggested that it may have a different disease phenotype, which has not been investigated before using a systematic approach. A systematic literature search of PubMed databases (updated to December 2016) was performed to identify all published data on the epidemiological, clinical and laboratory manifestations of pSS in the male and paediatric populations. The literature search of the male and paediatric pSS studies identified 2025 and 186 citations, respectively, out of which 7 and 5 fulfilled our inclusion criteria and were analysed further. The range of age at disease onset was 9.4–10.7 years for children and 39.4–56.9 years at diagnosis for male patients. We identified a prevalence of extra-glandular manifestations between 52.6–92.3% in the male population and 50.0–84.6% in children, while abnormal sialometry was only reported in the paediatric population, with a prevalence between 71.4 and 81.8%. There was a significant variation of positive serological markers, with anti-Ro antibodies reported between 15.7–75.0% and 36.4–84.6%, and anti-La antibodies between 5.6–51.7% and 27.3–65.4%, in the male and paediatric populations, respectively. The characteristics of pSS in the male and paediatric populations varied according to different studies. When compared to data available from pSS adult populations, children diagnosed with pSS reported less dryness and had a higher prevalence of parotitis, lymphadenopathy and systemic symptoms and male patients were younger at the time of diagnosis. This systematic review contributes to a better understanding of the epidemiology of pSS in rare populations. Large longitudinal cohort studies comparing male with female patients and adult with paediatric patients are needed

Tubulointerstitial nephritis in primary Sjögren syndrome: clinical manifestations and response to treatment

BACKGROUND: Primary Sjögren syndrome (pSS) is a common autoimmune condition which primarily affects epithelial tissue, often including the kidney causing either tubulointerstitial nephritis (TIN) or more rarely, an immune complex related glomerulonephritis. METHODS: We describe the clinical, biochemical and histological characteristics of 12 patients with pSS related TIN and their response to treatment with antiproliferative agents. All 12 patients were investigated and treated at the UCL Centre for Nephrology in London. RESULTS: All patients had TIN demonstrated via needle biopsy; immunophenotyping showed that the interstitial infiltrate was predominantly a CD4+ T-cell infiltrate. Urinary acidification testing demonstrated distal renal tubular acidosis in 8 patients. Proximal tubular dysfunction was present in 5 patients. All but 1 patient were treated with antiproliferative agents and most also with a reducing course of steroids. In the treated patients, there was a significant improvement in the serum creatinine and measured GFR. CONCLUSION: Patients with pSS TIN have significant renal impairment and other functional tubular defects. There is a mononuclear lymphocytic infiltrate on renal biopsy and this appears to be mainly a CD4+ T-cell infiltrate. Treatment with mycophenolate (and corticosteroids) improves the renal function in patients with pSS TIN