Up to 5-year retention of abatacept in Belgian patients with moderate-to-severe rheumatoid arthritis: a sub-analysis of the international, observational ACTION study.

Favorable efficacy and safety profiles have been demonstrated for abatacept in patients with rheumatoid arthritis (RA) in randomized controlled trials, but these data require validation during long-term follow-ups in routine clinical practice. This study explored long-term safety and retention rates in RA patients treated with intravenous abatacept in the Belgian cohort of the international AbataCepT In rOutiNe clinical practice (ACTION) study (NCT02109666). This non-interventional, observational, longitudinal study included Belgian patients aged ≥ 18 years with moderate-to-severe RA who started intravenous abatacept treatment as first- or second/further-line biologic therapy in routine clinical practice. Between October 2010 and December 2012, 141 patients were enrolled in this cohort, of whom 135 evaluable patients (6 biologic-naïve; 129 previously exposed to ≥ 1 prior biologic disease modifying anti-rheumatic drugs) were eligible for the descriptive analysis; 131/135 were included in the effectiveness analysis. Mean disease duration was 10.5 years (standard deviation 9.7) before abatacept initiation. RA patients presented with high disease activity and comorbidity rate, having failed multiple previous treatment options. In this cohort, the 5-year abatacept retention rate was 34% (95% confidence interval, 23-45%) per protocol, and 51% (95% confidence interval, 40-61%) when temporary discontinuations of abatacept > 84 days (n = 24) were not considered as treatment discontinuations. After 5 years of abatacept treatment, clinical outcomes were favorable [good/moderate European League Against Rheumatism (EULAR) responses in 91.7% patients]. No new safety signals were detected for abatacept in routine clinical practice. In this difficult-to-treat Belgian RA population, high retention rates, good clinical outcomes and favorable safety profile were observed with abatacept.

Bio-optimized Curcuma longa extract is efficient on knee osteoarthritis pain: a double-blind multicenter randomized placebo controlled three-arm study.

OBJECTIVES: Comparison of two doses of bio-optimized Curcuma longa extract (BCL) in the management of symptomatic knee osteoarthritis (OA). METHODS: A prospective, randomized, 3-month, double-blind, multicenter, three-group, placebo-controlled trial assessing Patient Global Assessment of Disease Activity (PGADA) and serum sColl2-1, a biomarker of cartilage degradation, as co-primary endpoints. Pain on visual analog scale (VAS), Knee injury and Osteoarthritis Outcome Score (KOOS), and paracetamol/non-steroidal anti-inflammatory drug (NSAID) consumption were used as secondary endpoints. RESULTS: One hundred fifty patients with knee OA were followed for 90 days. Low and high doses of BCL showed a greater decrease of PGADA than placebo. Analysis of sColl2-1 showed in the placebo and BCL low-dose groups, but not in the BCL high-dose group, a transient but non-significant increase of sColl2-1 between T0 and T1. Thereafter, in all groups, sColl2-1 decreased between T1 and T3 (all p < 0.01), but no difference between the groups was found. Pain reduction at day 90 in the low- and high-dose BCL groups (- 29.5 mm and - 36.5 mm) was higher than that in the placebo (- 8 mm; p = 0.018). The global KOOS significantly decreased overtime, but changes were comparable across treatment arms. The ratio of patients with adverse events (AE) related to the product was similar in the placebo and treatment groups, but the number of AE linked to the product was higher in the high-dose BCL group compared to the placebo (p = 0.012). CONCLUSIONS: BCL appeared safe and well-tolerated with no evidence of severe adverse effects. Efficacy analysis suggested positive trends for measurements of PGADA and serum levels of an OA biomarker and showed a rapid and significant decrease of pain in knee OA (Trial registration: ISRCTN, ISRCTN12345678. Registered 21 September 2016-retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02909621?term=osteoarthritis+curcumin&rank=5-Evaluation of FLEXOFYTOL® Versus PLACEBO (COPRA) NCT02909621).

Black pigments in the liver related to gold and titanium deposits. A report of four cases.

Black pigments are rarely described in the liver. We report four patients with chronic cholestasis and black pigments described on liver histological examination. Energy-dispersive X-ray analysis identified these black pigments as gold particles in the first three patients and titanium particles in the fourth. The origin of the gold deposits was unknown in this first patient and related to gold salts therapy in the two others. Titanium deposits was associated with hepatic granulomas and related to total knee replacement.

Anti-citrullinated peptide antibodies may occur in patients with psoriatic arthritis.

BACKGROUND: Anti-cyclic citrullinated peptide (anti-CCP) antibodies are considered highly specific markers of rheumatoid arthritis. Despite the high specificity of the test, anti-CCP antibodies have also been observed in psoriatic arthritis. OBJECTIVE: To determine the frequency of anti-CCP antibodies in psoriatic arthritis and to describe the clinical characteristics of such patients. METHODS: Serum samples from 192 patients with psoriatic arthritis were analysed for anti-CCP antibodies. A previously defined cut off point was applied at a specificity level of > or =98.5% (42 U/ml). Antibodies against pepA and pepB (two synthetic citrullinated peptides) were determined on samples containing anti-CCP antibodies by line immune assay. The swollen joint count and the numbers of affected joints (present or past) were recorded. Clinical features were noted and if available radiographs of hands and feet were scored for erosions. Rheumatoid factor was determined in all samples. RESULTS: Anti-CCP antibodies were found in 15 patients (7.8%); 13 of 15 anti-CCP2 positive samples were also positive for anti-pepA or pepB antibodies. The prevalence of anti-CCP antibodies was higher than expected in view of the highly specific cut off applied in the test. Detailed analysis of the clinical and radiological features makes it improbable that the high prevalence of anti-CCP antibodies resulted solely from concomitant psoriasis and rheumatoid arthritis or from misclassification. CONCLUSIONS: Anti-CCP antibodies may be present in patients with psoriatic arthritis. Although some of the present cohort could have had psoriasis with concomitant rheumatoid arthritis, a proportion at least had the typical characteristics of psoriatic arthritis as the primary diagnosis.

CARD15 gene polymorphisms in patients with spondyloarthropathies identify a specific phenotype previously related to Crohn's disease.

BACKGROUND: The association between spondyloarthropathy and Crohn's disease is well known. A risk for evolution to Crohn's disease has already been shown in the subgroup of patients with spondyloarthropathy associated with chronic gut inflammation. OBJECTIVE: To investigate whether the reported polymorphisms in the CARD15 gene, a susceptibility gene for Crohn's disease, are associated with the presence of preclinical intestinal inflammation observed in spondyloarthropathies. METHODS: 104 patients with spondyloarthropathies were studied. All underwent ileocolonoscopy with biopsies between 1983 and 2004. The prevalence of three single nucleotide polymorphisms in the CARD15 gene (R702W, G908R, and 1007fs) was assessed using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR); the patients were compared with an ethnically matched Crohn's disease population and a control population. RESULTS: The carrier frequency of R702W, G908R, or 1007fs variants in the spondyloarthropathy populations (20%) was similar to the control population (17%), but increased to 38% in the spondyloarthropathy subgroup with chronic gut inflammation. This frequency was significantly higher than in the other spondyloarthropathy subgroups (p = 0.001) or the control group (p = 0.006), but not different from the Crohn's disease group (49%) (NS). This indicates that CARD15 polymorphisms are associated with a higher risk for development of chronic gut inflammation. CONCLUSIONS: CARD15 gene polymorphisms clearly identify a subgroup of patients with spondyloarthropathies associated with chronic intestinal inflammation.

Radiological sacroiliitis, a hallmark of spondylitis, is linked with CARD15 gene polymorphisms in patients with Crohn's disease.

BACKGROUND: Sacroiliitis is a common extraintestinal manifestation of Crohn's disease but its association with the HLA-B27 phenotype is less evident. Polymorphisms in the CARD15 gene have been linked to higher susceptibility for Crohn's disease. In particular, associations have been found with ileal and fibrostenosing disease, young age at onset of disease, and familial cases. OBJECTIVES: To investigate whether the presence of sacroiliitis in patients with Crohn's disease is linked to the carriage of CARD15 polymorphisms. METHODS: 102 consecutive patients with Crohn's disease were clinically evaluated by a rheumatologist. Radiographs of the sacroiliac joints were taken and assessed blindly by two investigators. The RFLP-PCR technique was used to genotype all patients for three single nucleotide polymorphisms (SNP) in the CARD15 gene. Every SNP was verified by direct sequencing. The HLA-B27 phenotype was determined. RESULTS: Radiological evidence of sacroiliitis with or without ankylosing spondylitis was found in 23 patients (23%), of whom only three were HLA-B27 positive. In contrast, 78% of patients with sacroiliitis carried a CARD15 variant v 48% of those without sacroiliitis (p = 0.01; odds ratio 3.8 (95% confidence interval, 1.3 to 11.5)). Multivariate analysis (logistic regression) showed that the association between sacroiliitis and CARD15 polymorphisms was independent of other CARD15 related phenotypes (ileal and fibrostenosing disease, young age at onset of disease, familial Crohn's disease) (p = 0.039). CONCLUSIONS: CARD15 variants were identified as genetic predictors of Crohn's disease related sacroiliitis. An association was demonstrated between these polymorphisms and an extraintestinal manifestation of Crohn's disease.

Mosaic 13 trisomy due to de novo 13/13 translocation with subsequent fission. Karyotype: 46,XX,-13, +t(13;13)(p11;q11)/46,XX,del(13)(p11). A second example.

In this paper we report a second example of 13 trisomy mosaicism due to de novo 13/13 translocation followed by postzygotic fission of the translocation chromosome in a polymalformed female newborn.

Pipotiazine pharmacokinetics after p.o. and i.v. administration in man. Correlation between blood levels and effect on the handwriting area.

Plasma kinetics of pipotiazine, a phenothiazine neuroleptic, have been studied in five chronic schizophrenic patients after both oral (25 mg) and i.v. (5 mg) administration of pipotiazine tritiated in the 3- and 4-positions of the piperidine ring. Peak plasma concentrations of unchanged pipotiazine were reached between 1 and 2 h after oral administration and showed a five-fold inter-individual variation. The mean terminal elimination half-life was 11.2 h. After i.v. administration plasma concentration declined bi-exponentially with mean half-life values of 2.7 and 8.8 h. Data indicate that biotranformation of the drug was not dependent on the route of administration and that there were no qualitative differences in biotransformation between individuals. The large apparent distribution volumes (mean value 545 l) indicated extensive binding to tissue components. After 25 mg p.o. effect on the handwriting area was manifest from 8 to 48 h after administration and reached maximum intensity between 24 and 36 h. This is consistent with rather a large duration of action observed clinically.