Long-term durability and dose escalation patterns in infliximab therapy for psoriasis.

BACKGROUND: Infliximab often requires dose escalation to maintain response. Studies regarding long-term durability and dose escalation patterns for psoriasis are few. OBJECTIVE: We sought to evaluate dose escalation patterns in psoriatic patients to identify factors of lack of optimal response to infliximab. METHODS: A retrospective cohort study included 93 patients (216.3 patient-years) treated with infliximab for psoriasis. Kaplan-Meier analysis assessed drug durability. RESULTS: A median infliximab dose of 5.42 mg/kg/mo (range: 2.71-10.83) for a mean of 28 months was administered. Two thirds of patients received a dose escalation. Concurrent methotrexate extended duration of therapy (by a mean ± SD of 19.5 ± 8.1 months, P = .034), including time until first dose escalation (by a mean ± SD of 12.0 ± 6.1 months, P = .037), and failure (by a mean ± SD of 20.7 ± 6.7 months, P = .034). Patients who increased the infusion frequency before increasing the dose remained on infliximab 8.4 months longer than those who first increased the dose (P = .045). Four patients experienced adverse events; 2 required discontinuation. LIMITATIONS: Psoriasis Area and Severity Index, infliximab levels, and antibody titers were not measured. CONCLUSIONS: Dose escalation optimizes durability of infliximab. The probability of maintaining response is enhanced by concomitant methotrexate and increasing the infusion frequency before increasing the dose.

Cardiovascular Risk Factors and Echocardiographic Findings in a Predominantly Black Population with Rheumatoid Arthritis and Heart Failure.

Among White rheumatoid arthritis (RA) cohorts, heart failure with preserved ejection fraction (HFpEF) is the most prevalent type of heart failure (HF). We aimed to assess the type of HF affecting Black RA patients. 64 patients with RA-HF were compared to age-, sex-, and race-matched RA patients without HF. Left ventricular ejection fraction (LVEF), wall motion abnormalities, left ventricle (LV) mass, and wall thickness were reviewed. 87.3% were Black, 84.4% were women, with a mean age of 69.6 ± 1.38 (± SEM) and BMI (kg/m 2) 29.6 ± 1.07. RA-HF patients had higher rates of hypertension (HTN), chronic kidney disease, and atrial fibrillation. 66.7% had ≥3 cardiovascular risk factors compared to RA patients without HF. 2D-echocardiograms of RA-HF revealed that 62.3% had LVEF ≥50%, 37% had diastolic dysfunction, and 43.1% had wall motion abnormalities. LV mass and relative wall thickness measurements indicated LV eccentric remodeling. The odds ratio for HF was 4.7 (1.5-14.53 CI), p<0.01, among RA-HTN group and 3.5 (1.091-11.7 CI) p<0.01 among smokers. In our predominantly Black RA-HF patients, HFpEF was the most common type of HF. HTN was associated with the highest OR for HF. Eccentric hypertrophic remodeling, a known poor prognostic indicator for cardiovascular events, was found. Further studies are required to confirm our findings.

Dissection of immune gene networks in primary melanoma tumors critical for antitumor surveillance of patients with stage II-III resectable disease.

Patients with resected stage II-III cutaneous melanomas remain at high risk for metastasis and death. Biomarker development has been limited by the challenge of isolating high-quality RNA for transcriptome-wide profiling from formalin-fixed and paraffin-embedded (FFPE) primary tumor specimens. Using NanoString technology, RNA from 40 stage II-III FFPE primary melanomas was analyzed and a 53-immune-gene panel predictive of non-progression (area under the curve (AUC)=0.920) was defined. The signature predicted disease-specific survival (DSS P<0.001) and recurrence-free survival (RFS P<0.001). CD2, the most differentially expressed gene in the training set, also predicted non-progression (P<0.001). Using publicly available microarray data from 46 primary human melanomas (GSE15605), a coexpression module enriched for the 53-gene panel was then identified using unbiased methods. A Bayesian network of signaling pathways based on this data identified driver genes. Finally, the proposed 53-gene panel was confirmed in an independent test population of 48 patients (AUC=0.787). The gene signature was an independent predictor of non-progression (P<0.001), RFS (P<0.001), and DSS (P=0.024) in the test population. The identified driver genes are potential therapeutic targets, and the 53-gene panel should be tested for clinical application using a larger data set annotated on the basis of prospectively gathered data.

Practical pearls in phototherapy.

The following tips are suggested for phototherapy: (i) calibrate the unit with a radiometer every 2-4 weeks; (ii) change all bulbs at the same time every 8-10 months for regularly used machines or when the UV meter shows that the power has reached 3 or 4 mW/cm(2) ; (iii) avoid phototherapy sessions on consecutive days to prevent burn on burn; (iv) in the event of a burn, reduce the last PUVA or UVB dose by 50%, reinitiating when erythema has fully disappeared, which might take two days to two weeks; (v) nausea from oral psoralens can be avoided by taking it with a fixed amount of milk or food, taking an antiemetic with this meal prior to dosing, taking five ginger tablets 15 minutes before dosing, or dividing the dosage; (vi) to achieve 0.03% concentration of 8-methoxypsoralen for hand and foot soak PUVA, dissolve a 10-mg tablet or 1.0 cc of Oxsoralen(®) solution 1% in 3 l of water; and (vii) to achieve 0.000075% concentration of 8-methoxypsoralen for full-body soak PUVA, dissolve 60 mg 8-methoxypsoralen in 80 l of water (i.e. a bath tub).