ABSTRACT
OBJECTIVES: The retention of the anti-rheumatic agent tocilizumab (TCZ) has not been well documented in patients with rheumatoid arthritis (RA). We conducted an observational study to compare the retention of TCZ and anti-tumour necrosis factor (TNF) drugs in the treatment of patients with RA. METHOD: We reviewed continuation rates and causes of discontinuation of biological agents (biologics) by assessing medical records of patients with RA who were administered biologics at our institute from September 1999 to April 2012, using the Osaka University Biologics for Rheumatic Diseases (BiRD) registry. RESULTS: A total of 401 patients were included. TCZ, infliximab (IFX), etanercept (ETN), and adalimumab (ADA) were administered to 97, 103, 143, and 58 patients, respectively. There were some differences between the baseline characteristics of the groups. The median duration (range) of TCZ, IFX, ETN, and ADA administration was 2.5 (0.1-12.6), 1.9 (0.0-7.7), 2.9 (0.0-11.3), and 1.3 (0.0-3.4) years, respectively. Continuation rates for TCZ and ETN were significantly higher than those for IFX and ADA. Multivariate analyses showed that discontinuation due to lack or loss of efficacy was significantly less common in the TCZ group than in the other groups. Discontinuation due to overall adverse events was not significantly different between treatment groups. CONCLUSION: TCZ and ETN show better retention than IFX or ADA in the treatment of RA.
Subject(s)
Antibodies, Monoclonal, Humanized/pharmacokinetics , Antibodies, Monoclonal/pharmacokinetics , Arthritis, Rheumatoid/drug therapy , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adalimumab , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal, Humanized/administration & dosage , Arthritis, Rheumatoid/diagnosis , Cohort Studies , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Infliximab , Kaplan-Meier Estimate , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Risk Assessment , Severity of Illness Index , Treatment Outcome , Young AdultABSTRACT
GTP:AMP phosphotransferase (adenylate kinase isozyme 3, AK3) mutants were obtained by using the ability of AK3 to complement a temperature-sensitive mutation of Escherichia coli adenylate kinase (AKe). Five mutants, P16L, G19S, G91D, G91S, and P93L, had mutation sites located at two loops that are involved in substrate binding of the enzyme. P16L and G19S bearing changes at the first loop showed reduced affinity for both GTP and AMP, the extent of reduction being slightly higher for GTP than AMP. In contrast, G91S and P93L having alterations at the second loop had lower affinities for AMP. Only the alterations at the second loop strongly influenced the Vmax value of the enzyme. Another mutant, D163N, had a substitution at the site forming a salt bridge in adenylate kinase isozyme 1 (AK1), which influenced the Vmax as well as the Km values for both substrates. The kinetic characteristics of these mutants were comparable to those of the corresponding AK1 or AKe mutants. Furthermore, from the results of mutations T201P and T201A that had alterations in all the kinetic parameters of AK3 and from a comparison with the structure and the kinetic parameters of AKe, we expect that a residue(s) around Thr201 is involved in recognition of the base of nucleoside triphosphate.
Subject(s)
Mitochondria/enzymology , Nucleoside-Phosphate Kinase , Adenylate Kinase/metabolism , Binding Sites , Escherichia coli/genetics , Guanosine Triphosphate/metabolism , Isoenzymes/metabolism , Mutation/genetics , Nucleoside-Phosphate Kinase/genetics , Nucleoside-Phosphate Kinase/isolation & purification , Nucleoside-Phosphate Kinase/metabolismABSTRACT
Severe nephrotic syndrome developed in an 83-year-old Japanese man with Waldenström's macroglobulinemia. Treatment with corticoid remarkably improved the proteinuria. Autopsy disclosed no deposit of amyloid in the kidneys but a slight infiltration of atypical lymphocytes. A considerable number of glomeruli showed mesangial cell proliferation and global or segmental thickening of the basement membrane with occasional double tracks. Immunofluorescent studies revealed deposits of IgM but not IgG, IgA and C3 along the basement membrane in most glomeruli. Electron microscopy disclosed the splitting glomerular basement membrane and scattered electron-dense deposits.
Subject(s)
Nephrotic Syndrome/etiology , Waldenstrom Macroglobulinemia/complications , Aged , Aged, 80 and over , Amyloidosis , Humans , MaleABSTRACT
This study explored the pathogenesis of a transport defect of IgM into the lumen in a patient with selective IgA deficiency. In addition to the absence of IgM in the saliva, no IgM was localized on the luminal surface of colonic mucosa from the patient despite the presence of J chain-positive IgM cells. On tissue sections, IgM cells did not bind secretory component. The serum IgM also showed a negligible capacity to bind secretory component in vitro. Such abnormalities of IgM molecules as stated above seem to be clinicopathologically linked with IgA deficiency or its associated Sjögren's syndrome.
