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.

Effectiveness, safety and quality-of-life effects of guselkumab and ustekinumab in patients with psoriasis: Week 104 results from the non-interventional, prospective, German multicentre PERSIST study.

BACKGROUND: PERSIST was a prospective, non-interventional, real-world study of guselkumab and ustekinumab in adult patients with moderate-to-severe plaque psoriasis in Germany. OBJECTIVES: To examine effectiveness, safety and quality-of-life (QoL) outcomes to Week (W) 104 of treatment with guselkumab and ustekinumab in patients with moderate-to-severe plaque psoriasis. METHODS: Patients (≥18 years of age) received guselkumab or ustekinumab as per routine clinical practice. Outcomes to W104 were examined separately in guselkumab and ustekinumab recipients. An ad hoc exploratory analysis of outcomes with guselkumab versus ustekinumab was also performed following propensity score matching. RESULTS: Overall, 302 and 313 patients received guselkumab and ustekinumab, respectively. Patients in both cohorts experienced improvements in disease activity and QoL that were maintained to W104, with 64.7% and 63.6% of guselkumab- and 54.6% and 64.4% of ustekinumab-treated patients achieving a Psoriasis Area and Severity Index (PASI) 90 response and a Dermatology Life Quality Index (DLQI) 0/1 score, respectively. Propensity score matching yielded well-balanced baseline characteristics except for prior biologic use, which was higher in guselkumab versus ustekinumab recipients (51.7% vs. 32.0%). Achievement of PASI ≤1 at W104 was more common in guselkumab versus ustekinumab recipients (58.7% vs. 49.7%). The W104 PASI90 response rate was 65.6% with guselkumab and 56.0% with ustekinumab; corresponding rates for PASI100 were 44.3% and 28.5%. In guselkumab recipients, response rates were higher in biologic-naïve versus biologic-experienced patients (PASI90, 77.1% vs. 53.4%; PASI100, 55.0% vs. 33.0%). A high level of response for QoL outcomes was observed for both treatments. CONCLUSIONS: Ustekinumab and guselkumab led to improvements in physician-assessed and patient-reported outcomes that were sustained for up to 2 years, with no new safety signals identified. Following propensity score matching, greater improvements in PASI outcomes were observed with guselkumab versus ustekinumab. Improvements with guselkumab were highest in biologic-naïve patients, highlighting the value of early treatment.

Fibrinogen Haifa: fibrinogen variant with absence of protective effect of calcium on plasmin degradation of gamma chains.

The abnormal fibrinogen Haifa is characterized by the fact that calcium present during enzymatic digestion by plasmin does not protect the Haifa D gamma chain against further plasmin attack as it does in normal molecules. Since calcium binding to fibrinogen, ADP--platelet aggregation cofactor activity and gamma dimerization process induced by factor XIIIa are normal for fibrinogen Haifa, the corresponding sequences in the gamma chain are not involved. It seems rather that the anomaly resides near the gamma 302 plasmin cleavage site that is protected when calcium is bound to the gamma chain and that this affects the availability of the polymerization site located in the C terminal part of the chain.

Fibrinogen "Haifa" - a new fibrinogen variant. A case report.

A 30-year-old female presenting with arterial occlusions of the lower limbs was discovered to have a markedly abnormal thrombin time and reptilase time. Further investigations revealed the presence of a qualitatively abnormal fibrinogen. Two other family members who were completely asymptomatic had similar defects. The abnormal fibrinogen has been characterized and found to be a new variant and as such designated fibrinogen 'Haifa'.