Long‐term efficacy of biologics in the treatment of psoriasis: what do we really know?

Psoriasis is a chronic inflammatory condition that often requires life-long treatment. Conventional therapies have not fully met the needs of psoriatic patients, because of limited efficacy, adverse effects with cumulative use, and patient inconvenience. In the past decade, biologic immunotherapies have become accepted treatments for psoriasis as a result of perceived efficacy and safety on the part of patients and practitioners. However, most data on these medications come from relatively limited short-term trials. In this review, we will focus on the available long-term data on the efficacy of the biologic agents. We will emphasize the strengths and weakness of the available data of the biologic agents that are Food and Drug Administration (FDA)-approved for the treatment of moderate to severe psoriasis (alefacept, efalizumab, * etanercept, infliximab, and adalimumab), with the inclusion of a newer agent currently under FDA evaluation (ustekinumab).     

Immune biomarker panel monitoring utilizing IDO enzyme activity and CD4 ATP levels: prediction of acute rejection vs. viral replication events

Infections have become as important an event as acute rejection posttransplant for long-term allograft survival. Less invasive biomarkers tested so far predict risk for one event or the other, not both. We prospectively tested blood and urine monthly for 12 months posttransplant from children receiving a kidney transplant. The IDO enzyme pathway was assessed by MS assays using the ratio of product l-kyn to substrate trp. Kyn/trp ratios and blood CD4 T-cell ATP levels were correlated with acute rejection or major infection events or stable group (no events) in the next 30 days. The 25 subjects experienced six discrete episodes of acute rejection in five subjects and 16 discrete events of major infection in 14 subjects (seven BK viruria, six cytomegaloviremia, one EB and cytomegaloviremia, and two transplant pyelonephritis). Mean serum kyn/trp ratios were significantly elevated in the group that experienced acute rejection (p = 0.02). Within-subject analyses revealed that over time, urine kyn/trp ratios showed an increase (p = 0.01) and blood CD4-ATP levels showed a decrease (p = 0.007) prior to a major infection event. These pilot results suggest that a panel of biomarkers together can predict over- or under-immunosuppression, but need independent validation.     

Axillary Recurrence After Sentinel Node Biopsy

Background Sentinel node biopsy (SNB) has evolved as the standard of care in the surgical staging of breast cancer. This technique is accurate for surgical staging of axillary nodal disease. We hypothesized that axillary recurrence after SNB is rare and that SNB may provide regional control in patients with microscopic nodal involvement.Methods With institutional review board approval, SNB was performed with peritumoral injection of ^99mTc-labeled sulfur colloid. From 1996 to 2003, 1167 patients were entered into a prospective cancer database after surgical therapy; 916 patients consented to long-term follow-up. Fifty-two patients (5.7%) did not map successfully and were excluded, leading to a study population of 864 patients. The median follow-up was 27.4 months (range, 1–98 months).Results The median number of sentinel nodes harvested was 2, and 633 (73%) patients had negative sentinel nodes. Thirty (4.7%) of those sentinel node–negative patients underwent completion axillary dissection, whereas 592 (94%) patients were followed up with observation. A total of 231 (27%) had positive sentinel nodes: 158 (68%) of these patients underwent completion axillary dissection, and 73 (32%) were managed with observation alone. Two (.32%) patients who were sentinel node negative had an axillary recurrence; one of these patients had undergone completion axillary dissection. No patient in the observed sentinel node–positive group had an axillary recurrence (odds ratio, .37; P = .725).Conclusions On the basis of a median follow-up of 27.4 months, axillary recurrence after SNB is extraordinarily rare regardless of nodal involvement, thus indicating that this technique provides an accurate measure of axillary disease and may impart regional control for patients with node-positive disease.     

Stable pediatric kidney transplant recipients run higher urine indoleamine 2, 3 dioxygenase (IDO) levels than healthy children

Immune cells utilize the IDO enzymatic conversion of trp to kyn to determine T‐cell activation vs. anergy/apoptosis. In prior studies, urine IDO levels were higher in rejecting renal allografts than in stable state. However, urine IDO levels in healthy subjects or children are unknown. As a corollary to a larger longitudinal and prospective study of serum and urine IDO levels for transplant immune monitoring, here, we analyzed the difference between urine IDO levels in stable post‐transplant vs. healthy children. IDO levels were measured by tandem mass spectrometry and expressed as kyn/trp ratios. We compared one‐time urine samples, from 34 well children at general pediatric clinics, to the first‐month post‐transplant urine samples from 18 children, while in stable state (no acute rejection or major infection event in next 30 days). Urine kyn/trp ratios were significantly higher in stable children in first‐month post‐kidney transplant (median 16.6, range 3.9–44.0) vs. healthy children (median 9.2, range 3.51–17.0; p = 0.0057 by nonparametric Mann–Whitney test). Higher urine IDO levels even with stable transplant suggest a continuous ongoing low‐grade allorecognition/inflammatory process. Our data also provide baseline urine IDO levels in healthy subjects for use in future studies.