Effectiveness, safety and impact of guselkumab on sexuality and perceived stigmatization in patients with psoriasis in routine clinical practice: Week 28 results from the prospective German multicentre G-EPOSS study.

BACKGROUND: G-EPOSS is a prospective, non-interventional, German multicentre study of patients with moderate-to-severe plaque psoriasis receiving guselkumab, a therapeutic monoclonal antibody targeting interleukin-23, in a real-world setting. OBJECTIVES: The objective of the study was to evaluate the effectiveness and safety of guselkumab, including its impact on skin, health-related quality of life (HRQoL), sexuality, and perceived stigmatization. METHODS: Patients (≥18 years old) received guselkumab per routine clinical practice. The primary endpoint was the proportion of patients achieving absolute Psoriasis Area and Severity Index (PASI) ≤ 3 at Week (W)28. Secondary endpoint assessments over 28 weeks included the Nail Psoriasis Severity Index (NAPSI), anogenital Physician's Global Assessment (aPGA), and Dermatology Life Quality Index (DLQI). Sexuality and perceived stigmatization were assessed by patients using the Relationship and Sexuality Scale (RSS) and Perceived Stigmatization Questionnaire (PSQ), respectively. RESULTS: Overall, 293 patients were included in the evaluable set population. Mean age and disease duration were 45.6 and 17.6 years, respectively. At baseline, mean PASI, aPGA and DLQI scores were 15.3, 2.7 and 11.3, respectively. In total, 25.9% of patients had received a prior biologic. Overall, 83.0% of patients achieved PASI ≤ 3, and 56.2%/35.1% achieved PASI ≤ 1/PASI = 0, respectively, at W28. Among those with NAPSI ≥ 1 and aPGA ≥ 1 at baseline, NAPSI = 0 and aPGA = 0 were achieved by 39.2% and 61.1% of patients, respectively, and 61.4% of patients achieved DLQI 0-1 at W28. Improvements were observed over 28 weeks across individual items of the DLQI, RSS and PSQ, indicating improved HRQoL and sex life, and decreased perceived stigmatization. Based on DLQI Question (Q)9, 53.6% of patients experienced sexual difficulties at baseline, which decreased to 12.1% at W28. DLQI Q9 responses were consistent with RSS item responses, highlighting DLQI Q9 as a sentinel for sexual impairment. CONCLUSIONS: Guselkumab improved overall skin symptoms and HRQoL in patients with psoriasis and decreased sexual impairment and perceived stigmatization. No new safety signals were observed. STUDY CODE: CNTO1959PSO4008.

Concentration relationships of cefaclor in serum, interstitial fluid, bile, and urine of dogs.

The concentrations of cefaclor in the serum, urine, bile, and tissue fluids of the abdominal wall, kidney, and liver of dogs were compared over a 4-h period after oral administration of a single dose of this drug. The concentration of cefaclor in the soft-tissue interstitial fluid peaked 2 h after administration, thereby demonstrating a diffusion rate similar to those of other cephalosporins. Both urine and bile concentrations greatly exceeded the serum levels, whereas none of the tissue fluid concentrations were greater than the serum concentrations at the times of measurement.

Effects of serum lipid content on the binding of minocycline.

Minocycline was added to normal and hyperlipemic serum samples in concentrations of 1 approximately 10 mcg/ml. These specimens had similar protein contents. Chemically extractable minocycline was quantitated fluorometrically. Hyperlipemic serum (cholesterol 480 mg/100 ml; triglycerides 321 mg/100 ml) yielded an average of 50% less minocycline than did normal serum (cholesterol 170 mg/100 ml; triglycerides 114 mg/100 ml). When ultrafiltrates of serum containing 6, 12 and 20 mcg/ml minocycline were assayed microbiologically, it was evident that variations in serum triglyceride and cholesterol levels did not alter the ratio of bound to free drug. Minocycline appears to be reversibly associated with, and/or soluble in, triglyceride-cholesterol components of serum.

Concentration of cefamandole in serum interstitial fluid, bile, and urine.

Cefamandole readily diffuses from the serum into soft tissue interstitial fluid. The rate of diffusion differs little from that of cephalothin. The concentrations of antibiotic were greater in bile and urine during the entire period of study than is necessary to kill susceptible pathogenic bacteria present in these fluids.

Protein binding and concentrations of cephaloridine and cefazolin in serum and interstitial fluid of dogs.

Percentages of free and protein-bound cefazolin and cephaloridine in serum and interstitial fluid of dogs were determined by ultrafiltration and microbiologic assay. The percentages of cephaloridine and cefazolin bound to protein in serum were 10% and 80%, respectively. In interstitial fluid accumulating within tissue-embedded polypropylene capsules, 29% of cefazolin was bound to protein, and cephaloridine was unbound. Both antibiotics rapidly penetrated the interstitial fluid and attained measurable levels 5 min after intravenous administration. Levels of total cefazolin in the interstitial fluid were generally higher than those of cephaloridine; however, concentrations of free cephaloridine in the fluid exceeded the levels of free cefazolin after the first 15 min. Binding of anitbiotics by serum proteins does not restrict such agents to the intravascular space, since a highly protein-bound compound has been shown to penetrate interstitial fluid as readily as one that is minimally bound. It should be noted, however, that this penetration may be due primarily to the slow rate of binding of cefazolin to serum proteins.

Regional antibiotic infusion of the heart.

Regional arterial infusion of the heart and lung with an antibiotic did not increase the drug in the aortic serum to concentrations that would be clinically significant when compared with concentrations which can be attained by the intravenous method in a near normal functioning heart.

Antibiotic concentrations in hepatic interstitial and wound fluid.

This study in dogs using tissue-implanted capsules indicates that cephalothin, cefazolin, ampicillin and tetracycline are excreted in the bile, appearing in this fluid at concentrations greater than the concomitant serum levels. Hepatic interstitial fluid concentrations of these agents differed little from levels achieved in soft tissues elsewhere in the body, indicating that compounds which are concentrated in bile do not necessarily achieve high levels in the hepatic parenchyma. The selection of an antimicrobial agent for the therapy of hepatic parenchymal infection or obstructive cholecystitis should, therefore, be based on susceptibilities of the suspected organism rather than on the relative tendencies of various agents to be concentrated in bile.

Concentration of antibiotics in renal interstitial fluid: an experimental model.

In a new canine experimental model the time concentration relationship of cephalothin in serum, urine, soft tissue interstitial fluid (STIF) and renal interstitial fluid (RIF) were compared simultaneously. Antibiotic concentration in RIF was less than urinary levels but exceeded the serum concentration. Urinary antibiotic concentration does not necessarily reflect concentration in the renal interstitium. This model helps to understand the basic pharmacokinetics of antibiotics in the renal interstitium where pyelonephritis occurs.

Rate of binding of antibiotics to canine serum protein.

The time rates of binding of three antibiotics of similar chemical structure, each with differing degrees of protein binding, were determined. Cephaloridine, which is 10% bound by serum proteins, was bound at a more rapid rate than cephalothin, which is 40% bound by serum protein. Cefazolin, bound 80%, required for longest time period for maximum binding to occur. The rate of protein binding appears directly related to the total percentage bound. The data from this study indicate that prolonged rates of binding of highly protein-bound drugs may influence pharmacological studies.