Subcutaneous injection of infliximab CT-P13 results in stable drug levels within 14-day treatment cycle in Crohn's disease.

The new subcutaneous (sc) formulation of the infliximab (IFX) biosimilar CT-P13 results in homogeneous serum trough concentrations of IFX at steady state. The present study aimed to investigate in Crohn's disease (CD) patients the intra-individual variations of IFX drug levels at multiple time-points during 2 consecutive cycles of maintenance therapy with CT-P13 sc. PATIENTS AND METHODS: CD patients in clinico-biological remission under maintenance therapy with intravenous (iv) IFX/CT-P13 were switched to CT-P13 sc 8 weeks (W) after the last infusion. They were treated with CT-P13 sc, 120 mg every 2 W. Assessments were performed from 8 W after starting CT-P13 sc and patients had to attend 6 visits on 2 consecutive cycles of treatment (cycles A and B). Visits were scheduled on days 4-6 (visit 1), days 7-9 (visit 2) and day 14 (visit 3) of each cycle, where days 1 and 14 were the days of sc injection of CT-P13. At each visit, peripheral blood was collected to measure serum IFX levels and anti-drug antibodies. RESULTS: Twenty patients underwent 120 evaluations. Large intra-individual variations of serum drug levels of IFX were observed. When pooling the 120 evaluations, the mean drug level was 11.3 ± 4.9 µg/ml, and the median drug level was 10.9 µg/ml (IQR 7.5-15.5). During each cycle, the median drug levels were similar between visits 1 and 2 as well as between visits 1 and 3 and between visits 2 and 3. In cycle A, median drug levels were 11.1 µg/ml (7.8-14.5), 12.0 µg/ml (7.2-16.1) and 11.0 µg/ml (7.5-15.1) at V1, V2 and V3, respectively. Similar results were obtained in cycle B, where median drug levels were 11.6 µg/ml (7.9-14.9), 11.4 µg/ml (8.1-15.2) and 10.9 µg/ml (7.9-15.6) at V1, V2 and V3, respectively. In univariate analysis, we failed to identify factors predictive of low drug levels. CONCLUSIONS: IFX drug levels are quite stable within 14-day treatment cycle, without trough levels in CD patients in remission during the maintenance therapy with CT-P13 sc. In patients with inactive CD under maintenance therapy with CT-P13 sc, therapeutic drug monitoring of IFX can be performed at any time between two CT-P13 sc injections.

Comparison of Screening Dilution and Automated Reading for Antinuclear Antibody Detection on HEP2 Cells in the Monitoring of Connective Tissue Diseases.

BACKGROUND: Indirect immunofluorescence plays a major role in the detection of antinuclear antibodies (ANAs) and follow-up of their titers in the context of connective tissue diseases. Given the numerous unfavorable features of the conventional manual reading of HEP2 slides (need of time and expert morphologists for the reading, lack of standardization, subjectivity of the interpretation), the biomedical industry has developed automated techniques of slide preparation and microscope reading. METHODS: We collected 49 sera beforehand analyzed by the conventional reading of slides. They were prepared again by QUANTA-Lyser(®) and reanalyzed in four different conditions: two dilutions of screening (1/40 and 1/80), two different systems of analysis, NOVA View(®) automated reading (INOVA Diagnostics), then confirmation by the operator, and conventional manual reading by two different qualified operators. The analysis was realized in blind of the first interpretation and clinical diagnosis. The sera were classified in four groups, on the basis of the results of the first analysis: negative sera (titer < 1/160; 11 patients), low positives (titer at 1/160; 18 patients), moderated positives (titers between 1/320 and 1/640; 10 patients), and strong positives (titers between 1/1,280 and 1/2,560; 10 patients). RESULTS: Among the 49 patients, 13 presented a connective tissue disease including 4 systemic scleroderma (SS), 3 rheumatoid arthritis (RA), 2 Goujerot-Sjogren (GS), 2 systemic lupus erythematosus (SLE), 1 polymyositis (PM), 1 Raynaud's syndrome (RS), and 1 CREST syndrome. One patient presented both an SLE and an SS. Regarding the screening dilution, the 1/40 dilution is less specific than the 1/80 dilution for both the systems of analysis (5.6% vs. 16.7% for the manual reading, and 27.8% vs. 50% for the automated reading). It also generates statistically more false positives (P = 0.037 for the conventional analysis and P = 0.003 for the automated system). The automated NOVA View(®) reading of slides allows a gain in specificity for both dilutions, and also statistically less false positives (P = 0.002 at the 1/40 and P = 0.0006 at the 1/80), and detriment of the sensitivity at the highest dilution (84.6% vs. 92.3% with manual reading). Thus, according to our analysis of 49 sera, the automated NOVA View(®) system of reading of slides at the dilution 1/80 seems to be a successful condition for the detection of ANAs on HEP2 cells, close to the significance (P = 0.067). CONCLUSION: The automated NOVA View(®) reading of slides allows saving time, and an improvement in the standardization. Nevertheless, it requires a confirmation by a qualified operator, to interpret mixed patterns in particular.