Predictors of DAPSA28 remission in patients with psoriatic arthritis initiating a first TNF inhibitor: results from 13 European registries.

OBJECTIVES: In bio-naïve patients with PsA initiating a TNF inhibitor (TNFi), we aimed to identify baseline predictors of Disease Activity index for PsA in 28 joints (DAPSA28) remission (primary objective) and DAPSA28 moderate response at 6 months, as well as drug retention at 12 months across 13 European registries. METHODS: Baseline demographic and clinical characteristics were retrieved and the three outcomes investigated per registry and in pooled data, using logistic regression analyses on multiply imputed data. In the pooled cohort, selected predictors that were either consistently positive or negative across all three outcomes were defined as common predictors. RESULTS: In the pooled cohort (n = 13 369), 6-month proportions of remission, moderate response and 12-month drug retention were 25%, 34% and 63% in patients with available data (n = 6954, n = 5275 and n = 13 369, respectively). Five common baseline predictors of remission, moderate response and 12-month drug retention were identified across all three outcomes. The odds ratios (95% CIs) for DAPSA28 remission were: age, per year: 0.97 (0.96-0.98); disease duration, years (<2 years as reference): 2-3 years: 1.20 (0.89-1.60), 4-9 years: 1.42 (1.09-1.84), ≥10 years: 1.66 (1.26-2.20); men vs women: 1.85 (1.54-2.23); CRP of >10 vs ≤10 mg/l: 1.52 (1.22-1.89) and 1 mm increase in patient fatigue score: 0.99 (0.98-0.99). CONCLUSION: Baseline predictors of remission, response and adherence to TNFi therapy were identified, of which five were common for all three outcomes, indicating that the predictors emerging from our pooled cohort may be considered generalizable from country level to disease level.

Do biologic drugs affect the need for and outcome of joint replacements in patients with rheumatoid arthritis? A register-based study.

OBJECTIVES: The aim was to study the incidence of joint replacements among biologic drug and disease-modifying anti-rheumatic drug (DMARD) users as well as to investigate the plausible effect of biologic treatment on survival of prostheses in patients with Rheumatoid arthritis (RA). METHODS: The study population comprised 2 cohorts of patients [Register of biologic treatment in Finland (ROB-FIN) and the Central Finland RA database] from 1999 to 2010. Records of joint replacements performed in the study population between 1980 and 2010 were retrieved from the Finnish Arthroplasty Register. Propensity score matching was used to equalize patient characteristics between biologics and DMARD users. The incidence rates of primary and revision operations were compared between the 2 treatment groups. Kaplan-Meier survival analysis was used to analyze prosthesis survival. RESULTS: Of the 2102 biologics and 2710 DMARD users identified from the registries, 1587 were included in both groups after the matching. Median follow-up times were 3.1 and 8.0 years, respectively. There were more primary operations per 100 patient years in the biologics (3.89, CI 95% 3.41-4.41) vs. DMARD (2.63, 2.35-2.94) group but slightly fewer revisions (0.65, 0.46-0.88 vs. 0.83, 0.68-1.01). Biologics users were more likely to receive a joint replacement to small joints (p < 0.001). The survival of the prostheses installed during or prior to follow-up was similar in both treatment groups. CONCLUSIONS: The use of biologic drugs did not reduce the need for joint replacement surgery in patients with a similar on-medication disease activity. Despite possibly lower rate of revisions among biologic users, the durability of prostheses was not improved.

Biodistribution and radiation dosimetry of [(11)C]choline: a comparison between rat and human data.

PURPOSE: Methyl-(11)C-choline ([(11)C]choline) is a radiopharmaceutical used for oncological PET studies. We investigated the biodistribution and biokinetics of [(11)C]choline and provide estimates of radiation doses in humans. METHODS: The distribution of [(11)C]choline was evaluated ex vivo in healthy rats (n=9) by measuring the radioactivity of excised organs, and in vivo in tumour-bearing rats (n=4) by PET. In addition to estimates of human radiation doses extrapolated from rat data, more accurate human radiation doses were calculated on the basis of PET imaging of patients with rheumatoid arthritis (n=6) primarily participating in a synovitis imaging project with [(11)C]choline. Dynamic data were acquired from the thorax and abdomen after injection of 423+/-11 MBq (mean+/-SD) of tracer. Following PET imaging, the radioactivity in voided urine was measured. The experimental human data were used for residence time estimations. Radiation doses were calculated with OLINDA/EXM. RESULTS: In rats, the radioactivity distributed mainly to the kidneys, lungs, liver and adrenal gland. The effective dose in a human adult of about 70 kg was 0.0044 mSv/MBq, which is equivalent to 2.0 mSv from 460 MBq of [(11)C]choline PET. The highest absorbed doses in humans were 0.021 mGy/MBq in the kidneys, 0.020 mGy/MBq in the liver and 0.029 mGy/MBq in the pancreas. Only 2.0% of injected radioactivity was excreted in the urine during the 1.5 h after injection. CONCLUSION: The absorbed radiation doses after administration of 460 MBq of [(11)C]choline were low. Except for the pancreas, biodistribution in the rat was in accordance with that in humans, but rat data may underestimate the effective dose, suggesting that clinical measurements are needed for a more detailed estimation. The observed effective doses suggest the feasibility of [(11)C]choline PET for human studies.

Use of positron emission tomography with methyl-11C-choline and 2-18F-fluoro-2-deoxy-D-glucose in comparison with magnetic resonance imaging for the assessment of inflammatory proliferation of synovium.

OBJECTIVE: To compare positron emission tomography (PET) and magnetic resonance imaging (MRI) in the evaluation of inflammatory proliferation of synovium. METHODS: Ten patients (mean +/- SD age 36 +/- 13 years) with inflammatory joint disease and with clinical signs of inflammation of the joint were studied. A new tracer for cellular proliferation, methyl-(11)C-choline ((11)C-choline), and a widely used tracer for the detection of inflammation and cancer, 2-(18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG), were applied for PET imaging, and the results were compared with the findings from gadolinium diethylenetriaminepentaacetic acid-enhanced MR images. The uptake of (11)C-choline and (18)F-FDG in the inflamed synovium was measured and expressed as the standardized uptake value (SUV) and the kinetic influx constant (K(i)) obtained from graphic analysis, and these values were compared with quantitative values on MRI. Synovial volumes were measured on the coronal contrast-enhanced T1-weighted MR images using the standard software of the MR imager. RESULTS: All patients showed high accumulation of both (11)C-choline and (18)F-FDG at the site of arthritic changes, where quantification of the tracer uptake was performed. The SUV of (11)C-choline was 1.5 +/- 0.9 gm/ml (mean +/- SD; n = 10) and the SUV of (18)F-FDG was 1.9 +/- 0.9 gm/ml (n = 10) (P = 0.017). The K(i) of (11)C-choline (mean +/- SD 0.048 +/- 0.042 minute(-1)) was 8-fold higher than the K(i) of (18)F-FDG (0.006 +/- 0.003 minute(-1)) (P = 0.009). Both the uptake of (11)C-choline and the uptake of (18)F-FDG correlated highly with the volume of synovium; the highest correlation was observed with the K(i) of (11)C-choline (r = 0.954, P < 0.0001). CONCLUSION: In the use of PET scans,(11)C-choline can be regarded as a promising tracer for quantitative imaging of proliferative arthritis changes. Nevertheless, subsequent prospective studies with larger numbers of patients are necessary to further characterize the relationship between the findings on PET imaging and the clinical and functional measures of inflammation.