Objective. To establish proper management of Pneumocystis jiroveci pneumonia (PCP) in rheumatoid arthritis (RA) patients treated with infliximab. PCP has been observed in 0.4% of patients with RA treated with infliximab in Japan. Methods. Data from patients with RA (n ‫؍‬ 21) who were diagnosed with PCP during infliximab treatment and from 102 patients with RA who did not develop PCP during infliximab therapy were collected from 14 rheumatology referral centers in Japan. A retrospective review of these patients and a case-control study to compare patients with and without PCP were performed. Results. The median length of time from the first infliximab infusion to the development of PCP was 8.5 weeks. At the onset of PCP, the median dosages of prednisolone and methotrexate were 7.5 mg/day and 8 mg/week, respectively. Pneumocystis jiroveci was microscopically identified in only 2 patients, although the polymerase chain reaction test for the organism was positive in 20 patients. The patients with PCP had significantly lower serum albumin levels (P < 0.001) and lower serum IgG levels (P < 0.001) than the patients without PCP. Computed tomography of the chest in all patients with PCP revealed ground-glass opacity either with sharp demarcation by interlobular septa or without interlobular septal boundaries. Sixteen of the 21 patients with PCP developed acute respiratory failure, but all survived. Conclusion. PCP is a serious complication that may occur early in the course of infliximab therapy in patients with RA. For the proper clinical management of this infectious disease, physicians need to be aware of the possibility of PCP developing during infliximab therapy.

Objectives. To demonstrate the pharmacokinetic equivalence of CT-P13 and its innovator infliximab (IFX) in Japanese patients with rheumatoid arthritis (RA), and to compare the efficacy and safety of these drugs, administered for 54 weeks. Methods. In a randomized, double-blind, parallel-group, multicenter study, 3 mg/kg of CT-P13 or IFX, in combination with methotrexate (MTX) (6–16 mg/week), was administered for 54 weeks to Japanese active RA patients with an inadequate response to MTX, to demonstrate the pharmacokinetic equivalence, based on the area under the curve (AUCτ) (weeks 6–14) and Cmax (week 6) of these drugs, and to compare their efficacy and safety. Results. The CT-P13-to-IFX ratios (90% confidence intervals) of the geometric mean AUCτ and Cmax values in patients negative for antibodies to infliximab at week 14 were 111.62% (100.24–124.29%) and 104.09% (92.12–117.61%), respectively, demonstrating the pharmacokinetic equivalence of these drugs. In the full analysis set, CT-P13 and IFX showed comparable therapeutic effectiveness, as measured by the American College of Rheumatology, Disease Activity Score in 28 joints, the European League Against Rheumatism, and other efficacy criteria, at weeks 14 and 30. The incidence of adverse events was similar for these drugs. Conclusion. CT-P13 and IFX, administered at a dose of 3 mg/kg in combination with MTX to active RA patients, were pharmacokinetically equivalent and comparable in efficacy and safety.

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Summary. We previously demonstrated that interleukin 2 (IL‐2) autocrine/paracrine growth in adult T‐cell leukaemia (ATL) cells was closely correlated with clinical aggressiveness. In the present study, we compared the significance of IL‐15 and IL‐2 in growth of ATL cells and clinical aggressiveness. Thirty‐seven patients with ATL were examined: 19 acute and 18 chronic. Autonomous growth and IL‐2‐ or IL‐15‐responsive growth activities of ATL cells were measured by [3H]‐thymidine incorporation after 24 h cultures in vitro. All of the autonomous, IL‐15‐ and IL‐2‐responsive growth activities of acute‐type cells were higher than those of chronic type (P = 0·04, P = 0·03 and P = 0·02 respectively). IL‐15‐ and IL‐2‐responsive growth activities were highly correlated (P = 0·0001, R2 = 0·837). Enzyme‐linked immunosorbent assay (ELISA) showed detectable serum levels of IL‐15 and IL‐2 in 18 out of 19 and 14 out of 17 patients respectively. Reverse transcription polymerase chain reaction (RT‐PCR) revealed IL‐15 and IL‐2 mRNA expression in 8 out of 11 patients' cells. Anti‐IL‐2 antibody partially inhibited autonomous growth of ATL cells; anti‐IL‐15 antibody was less effective. In situ immunochemistry detected IL‐15 in cells of three patients and was consistent with the results of RT‐PCR. These results suggest that ATL cells grow in an IL‐15 autocrine/paracrine manner and that this growth is related to disease aggressiveness in a manner similar to IL‐2.

Four groups of eight infants (3 weeks of age on average) were each habituated to one of four displays consisting of a grating of either low (0.4 cpd) or high (1.2 cpd) spatial frequency, whose central portion was covered up with a horizontal occluder which was either narrow (1.33 degrees) or broad (4.17 degrees). These habituation displays are referred to as LN (low spatial frequency grating and narrow occluder), LB (low and broad), HN (high and narrow), and HB (high and broad) displays. Posthabituation-test displays consisted of a complete grating (CG) of the same frequency as the habituated grating along with a separate grating (SG) whose central portion was replaced with a black gap of the same height as the occluder in the habituation displays. Infants habituated to the LN display looked significantly longer at the SG than the CG display during posthabituation-test trials. Infants habituated to the LB and HN displays looked at the CG and SG displays, almost equally. In contrast, infants habituated to the HB display looked longer at the CG than the SG display. These results show that infants under 1 month of age can perceive the continuation of the grating behind the occluder, and that their visual completion on habituation displays can be evoked according to the interaction between the spatial frequency of the grating and the occluder height.