Efficacy and safety of tildrakizumab for the treatment of moderate-to-severe plaque psoriasis of the scalp: A multicenter, randomized, double-blind, placebo-controlled, Phase 3b study.

BACKGROUND: Scalp psoriasis is common and difficult to treat. OBJECTIVE: To evaluate efficacy and safety of tildrakizumab for the treatment of scalp psoriasis. METHODS: In this Phase 3b, randomized, double-blind, placebo (PBO)-controlled study (NCT03897088), patients with moderate-to-severe plaque psoriasis affecting the scalp (Investigator Global Assessment modified [IGA mod] 2011 [scalp] ≥3, Psoriasis Scalp Severity Index [PSSI] ≥12, ≥30% scalp surface area affected) received tildrakizumab 100 mg or PBO at W0 and W4. The primary endpoint was IGA mod 2011 (scalp) score of "clear" or "almost clear" with ≥2-point reduction from baseline at W16 (IGA mod 2011 [scalp] response). Key secondary endpoints were PSSI 90 response at W12 and W16 and IGA mod 2011 (scalp) response at W12. Safety was assessed from adverse events. RESULTS: Of patients treated with tildrakizumab (n = 89) vs PBO (n = 82), 49.4% vs 7.3% achieved IGA mod 2011 (scalp) response at W16 (primary endpoint) and 46.1% vs 4.9% at W12; 60.7% vs 4.9% achieved PSSI 90 response at W16 and 48.3% vs 2.4% at W12 (all P < .00001). No serious treatment-related adverse events occurred. LIMITATIONS: Only short-term data are presented. CONCLUSION: Tildrakizumab was efficacious for the treatment of scalp psoriasis with no new safety signals.

Oral spleen tyrosine kinase/Janus Kinase inhibitor gusacitinib for the treatment of chronic hand eczema: Results of a randomized phase 2 study.

BACKGROUND: Gusacitinib is an oral inhibitor of Janus and Spleen tyrosine kinases. METHODS: The efficacy and safety of gusacitinib were evaluated in a double-blind, placebo-controlled, multicenter, phase 2 study in 97 chronic hand eczema patients randomized (1:1:1) to placebo or gusacitinib (40 or 80 mg) for 12 weeks (part A). Then, in part B (through week 32), the patients received gusacitinib. RESULTS: At week 16, patients receiving 80 mg gusacitinib showed a 69.5% (P <.005) decrease in the modified total lesion-symptom score versus 49.0% for 40 mg (P =.132), and 33.5% for placebo. Considerable improvement in Physician's Global Assessment was seen in 31.3% of patients receiving 80 mg versus 6.3% of placebo (P <.05). A 73.3% decrease in the hand eczema severity index versus placebo (21.7%) occurred in patients receiving 80 mg (P <.001). Patients receiving 80 mg experienced a considerable decrease in hand pain (P <.05). As early as week 2, considerable reductions over placebo in modified total lesion-symptom score (P <.005), Physician's Global Assessment (P =.04), and hand eczema severity index (P <.01) were observed (80 mg gusacitinib). Adverse events included upper respiratory infection, headache, nausea, and nasopharyngitis. CONCLUSIONS: Gusacitinib showed rapid improvement in chronic hand eczema patients and was well tolerated, warranting further investigations.

Perspectives on Living with Chronic Spontaneous Urticaria: From Onset through Diagnosis and Disease Management in the US.

Chronic spontaneous urticaria is challenging to manage and substantially affects quality of life. This US, non-interventional qualitative study examined patients' clinical journeys and emotional burden from symptom onset through disease management. Chronic spontaneous urticaria patients participated in interviews and completed diaries focusing on disease and treatment history/perspectives, impact on personal/family life, and relationships with physicians/other healthcare providers. Physicians were interviewed about their views on disease management and patient care. Twenty-five patients, previously or currently receiving chronic spontaneous urticaria treatment(s), and 12 physicians participated. Key stages following symptom onset were identified: Crisis (associated with feelings of torment/disorientation/shock); Searching for answers (puzzlement/frustration/anxiety); Diagnosis (relief/satisfaction/fear/isolation); and Disease management (frustration/hope/powerlessness). Findings revealed patients' perceptions and experiences of chronic spontaneous urticaria, including living with a 'skinemy', experiencing their 'own personal hell' and feeling 'like an experiment'. Awareness of unmet needs in patient care/management identified in this study may ultimately improve patient support and enhance physicians' understanding of disease burden.

Effect of infliximab on health-related quality of life and disease activity by body region in patients with moderate-to-severe psoriasis and inadequate response to etanercept: results from the PSUNRISE trial.

BACKGROUND: Treatment with tumor necrosis factor (TNF)-α antagonists is effective in patients with moderate-to-severe plaque psoriasis, including those with impaired health-related quality of life (HRQoL). METHODS: PSUNRISE is a multicenter, open-label, prospective study evaluating the efficacy and safety of switching from etanercept to infliximab in psoriasis patients with an inadequate response to etanercept. Patients received intravenous infusions of infliximab 5 mg/ kg at weeks 0, 2, 6, 14, and 22. HRQoL was assessed using the Dermatology Life Quality Index (DLQI), the 36-item Short-Form Health Survey (SF-36), and the EuroQoL (EQ-5D) index and EQ-5D visual analog scale (VAS; 0-100 cm) among patients receiving at least one infliximab infusion. Subgroup analyses (t- test) were performed to compare mean DLQI improvement between patients who achieved and did not achieve clinical response (Physician's Global Assessment [PGA] 0/1 and at least a 75% improvement in the Psoriasis Area and Severity Index [PASI 75]) at weeks 10 and 26. RESULTS: A total of 215 patients received at least one infliximab infusion. A DLQI score of 0 or 1 (no negative effect on HRQoL) was achieved by 3.7%, 44.2%, and 41.4% of patients at weeks 0, 10 and 26, respectively. Mean changes in SF-36 Physical Component Summary scores were 1.8 (week 10) and 2.4 (week 26); corresponding changes in Mental Component Summary scores were 4.5 and 5.0. The mean change in EQ-5D index score was 0.08 at week 10 and 0.09 at week 26; respective mean changes in EQ-5D VAS score were 7.73 and 9.49. Mean improvements in DLQI were significantly higher for patients achieving versus those not achieving PGA 0/1 (P=0.0193 [week 10] and P=0.0010 [week 26]) and PASI 75 response (P<0.0001 [week 10]; P=0.0012 [week 26]). CONCLUSION: Psoriasis patients with prior inadequate response to etanercept demonstrated sustained improvements in HRQoL after switching to infliximab, and HRQoL improvements were associated with clinical responses.

The efficacy and safety of infliximab in patients with plaque psoriasis who had an inadequate response to etanercept: results of a prospective, multicenter, open-label study.

BACKGROUND: In patients with psoriasis and inadequate response (IR) to tumor necrosis factor-α antagonist treatment, the incremental benefit of switching to another tumor necrosis factor-α antagonist is unknown. OBJECTIVE: We sought to evaluate the clinical response to an etanercept-to-infliximab switch in patients with psoriasis and IR to etanercept. METHODS: Adults with moderate-to-severe plaque psoriasis and IR to etanercept (≥ 4 months) were eligible for this open-label study (called PSUNRISE). Patients had a Physician Global Assessment (PGA) score of at least 2 (mild) on a 5-point scale with etanercept, with or without concomitant oral systemic methotrexate or cyclosporine at baseline and during the study. Patients received intravenous infusions of infliximab 5 mg/kg at weeks 0, 2, 6, 14, and 22. PGA was used to evaluate efficacy at week 10 (primary end point) and week 26 (durability). Safety was evaluated through the end of the study. RESULTS: Of 215 patients, only 10 received concomitant immunomodulators. At week 10, 65.4% of patients (138 of 211; 95% confidence interval 58.6%-71.8%) achieved a PGA score of clear (0) or minimal (1) (primary end point). This response was durable through week 26, at which time 61.3% (122 of 199; 95% confidence interval 54.2%-68.1%) achieved a PGA score of clear (0) or minimal (1). There were no unexpected side effects or safety concerns. LIMITATIONS: This was an open-label, 26-week study; an incremental change of 1 PGA point, even mild to minimal, was considered clinically significant, as most psoriasis practitioners seek to achieve minimal psoriasis or clear skin. CONCLUSION: After switching to infliximab, a substantial proportion of patients with psoriasis and IR to etanercept experienced rapid and durable improvement.