Interval prolongation of etanercept in rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis: a randomized controlled trial.

OBJECTIVE: The majority of patients with a rheumatic disease treated with etanercept may be overexposed. Data regarding etanercept tapering are scarce, particularly in psoriatic arthritis (PsA) and ankylosing spondylitis (AS). We compared extending the dose interval to continuation of the standard dose and studied the success rate of etanercept discontinuation. Etanercept concentrations were measured throughout the study. METHOD: 160 patients with rheumatoid arthritis (RA), PsA, or AS with sustained minimal disease activity (MDA) were enrolled in this 18-month, open-label, randomized controlled trial. The intervention group doubled the dosing interval at baseline and discontinued etanercept 6 months later. The control group continued the standard dose for 6 months and doubled the dosing-interval thereafter. The primary outcome was the proportion of patients maintaining MDA at 6 month follow-up. RESULTS: At 6 months, MDA status was maintained in 47 patients (63%) in the intervention group and 56 (74%) in the control group (p = 0.15), with comparable results in all rheumatic diseases. And median etanercept concentrations decreased from 1.50 µg/mL (interquartile range 1.06- 2.65) to 0.46 µg/mL (0.28-0.92). In total, 40% discontinued etanercept successfully with maintained MDA for at least 6 months. CONCLUSION: Etanercept tapering can be done without losing efficacy in RA, PsA, and AS patients in sustained MDA. A substantial proportion of patients could stop etanercept for at least 6 months. In many patients, low drug concentrations proved sufficient to control disease activity. However, the risk of minor and major flares is substantial, even in patients continuing standard dosing.

IgG4:IgG RNA ratio differentiates active disease from remission in granulomatosis with polyangiitis: a new disease activity marker? A cross-sectional and longitudinal study.

OBJECTIVES: An important limitation in granulomatosis with polyangiitis (GPA) is the lack of disease activity markers. Immunoglobulin G4-positive (IgG4+) B cells and plasma cells are implicated in the pathogenesis of GPA. We hypothesized that the presence of these cells in peripheral blood could serve as disease activity parameter in GPA. METHODS: We included 35 proteinase 3-antineutrophil cytoplasmic antibodies-positive patients with GPA in a cross-sectional study. Active disease was defined as Birmingham Vasculitis Activity Score (BVAS) ≥ 3 (n = 15), remission as BVAS of 0 (n = 17), and low disease activity (LDA) as BVAS of 1-2 and clinical remission (n = 3). Healthy subjects (n = 10), patients with systemic lupus erythematosus (n = 24), and patients with rheumatoid arthritis (n = 19) functioned as control subjects. An additional longitudinal study was performed in ten patients with GPA. Using a validated qPCR test, we measured the IgG4:IgG RNA ratio in all groups and compared the results with known biomarkers. RESULTS: The median qPCR score was higher in active GPA (21.4; IQR 12.1-29.6) than in remission/LDA (3.3; IQR 1.6-5.6) (Mann-Whitney U test, p < 0.0001) and outperformed other known disease activity parameters in detecting activity. A cutoff qPCR score of 11.2% differentiated active disease from remission/LDA accurately (AUC 0.993). The qPCR test correlated well with the BVAS (Spearman r = 0.77, p < 0.0001). In the longitudinal study, a decrease in BVAS correlated with qPCR score reduction (paired t test, p < 0.05). CONCLUSIONS: The IgG4:IgG RNA ratio in GPA accurately distinguishes active disease from remission and correlates well with disease activity in these single-center studies. If these results are confirmed in larger longitudinal studies, this test might help to steer treatment decisions in patients with GPA.

Biologics for rare inflammatory diseases: TNF blockade in the SA PHO syndrome.

INTRODUCTION: SAPHO is an invalidating syndrome characterised by Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis. The low prevalence and heterogeneous presentation often leads to a significant diagnostic delay. Here, we provide an up-to-date overview of current insights into the pathogenesis and different treatment options. In addition, we describe the effects of anti-TNF treatment in three refractory cases. CASE REPORTS: Patient A is a 25-year-old female with hidradenitis suppurativa, inflammatory back pain and painful joints. After diagnosis, anti-TNF treatment was started resulting in clinical improvement. Patient B is a 44-year-old woman who presented with acne, palmoplantar pustulosis and anterior chest wall pain. Bone scintigraphy showed increased uptake at the anterior chest wall. Treatment with bisphosphonates resulted in temporary improvement and subsequent treatment with anti-TNF induced long-term clinical improvement. Patient C is a 37-year-old woman with palmoplantar psoriasis, relapsing hidradenitis and inflammatory back pain. MRI revealed osteitis of the pubic bone. Anti-TNF was started for SAPHO syndrome. However, despite a clinical response, our patient discontinued treatment, resulting in rapid deterioration. Anti-TNF treatment was re-introduced followed by clinical improvement. CONCLUSION: These case reports illustrate, consistent with the current literature, that TNF blockers can be considered for treatment of refractory SAPHO syndrome.

Long-term follow-up after biliary stent placement for postoperative bile duct stenosis.

BACKGROUND: The outcome of temporary biliary stent placement for postoperative bile duct stenosis was retrospectively evaluated with the main aim of assessing long-term complications after stent removal. METHODS: ERCP was performed between 1981 and 1991 in 74 patients with postoperative bile duct stenoses. Two 10F stents were inserted for a maximum of 12 months with stent exchange every 3 months to avoid cholangitis caused by clogging. RESULTS: Stent insertion failed in 11 patients with complete and 4 patients with incomplete biliary obstruction. Early complications occurred in 14 patients (19%) including 2 deaths. Therefore 57 patients were included in the stent phase of the study. In 10 patients the referring physician did not adhere to the treatment protocol, and nonelective stent exchange for jaundice and/or cholangitis was necessary in 7 (70%). Of the 47 patients treated according to protocol, complications developed in 40% during the period with stents in situ. Stents were eventually removed in 44 patients who were subsequently followed for a median of 9.1 years. Late complications developed in 15 patients (34%) including recurrent stenosis in 9 (20%). All cases of recurrent stenosis occurred within 2 years of stent removal. CONCLUSIONS: Endoscopic treatment is feasible in 80% of patients who undergo an ERCP for postoperative bile duct stenosis. After stent insertion and during the time with stents in situ, complications occur at a significant rate but are usually mild or reflect the patient's underlying condition. After stent removal, recurrent stenosis develops in 20% of patients within 2 years of stent removal. Endoscopic treatment should be the initial management of choice for postoperative bile duct stenosis.