British Journal of Dermatology最新文献

Background: Cutaneous T-cell lymphomas (CTCL) are rare with distinct diagnostic challenges. Equitable access to cancer care is a recognised priority, internationally. To date, the geospatial distribution of CTCL has not been definitively studied. Understanding the incidence and geographical distribution of patients with CTCL are critical first steps towards the ultimate goal of equity of care. Geospatial analyses also allow the opportunity to explore environmental causative factors: for CTCL, the contribution of ultraviolet (UV) radiation on causation remains unclear.

Objectives: We investigate geospatial patterns of CTCL incidence across Australia, compare to all rare cancers, and consider solar UV exposure on causality and diagnosis rates.

Methods: All CTCL diagnoses (1/1/2000-31/12/2019) were obtained from the nation-wide dataset. Areas of residence were collected according to nationally-approved definitions. Bayesian spatial incidence models were applied. Geospatial distributions were visually analysed.

Results: The CTCL age-standardised incidence was 7.7 [95%CI:7.4-7.9] per million people in Australia. Diagnostic disparity was seen between Australian states/territories, with lower diagnosis rates in rural/remote and socio-economically disadvantaged areas. Incidence exceeded the national average within more densely populated capital cities. Visual comparisons of the geospatial distribution of CTCL revealed marked discordances with the geospatial patterns of all rare cancers and solar UV in Australia.

Conclusions: Geographical heterogeneity in CTCL exists across Australia. Incidence reflects population density. Geospatial patterns of CTCL substantially differ from all rare cancers, with implications for the unique diagnostic challenges and unmet needs of this patient population. The distribution of CTCL across Australia does not support a causative link with UV exposure. Further global evaluation of geospatial patterns is warranted.

Background: Approved tralokinumab maintenance dosing regimens for treatment of moderate-to-severe atopic dermatitis (AD) include 300 mg every two weeks (Q2W) and every four weeks (Q4W), that clinicians may consider for patients who achieved clear or almost clear skin at Week 16 with initial Q2W dosing.

Objectives: To identify predictive factors associated with maintained response after switching to tralokinumab Q4W, evaluate recapture of treatment response after relapse on Q4W, and assess treatment-emergent immunogenicity with tralokinumab Q4W.

Methods: These post hoc analyses utilized machine learning to identify predictive factors for maintained treatment response at Week 52 using data from the Week 16 responder population (ie, patients who met Investigator's Global Assessment of clear/almost clear skin [IGA 0/1] and/or ≥75% improvement in Eczema Area and Severity Index (EASI-75) at Week 16 with tralokinumab Q2W monotherapy) of the phase 3 ECZTRA 1 and 2 trials. Top-ranked factors were then assessed individually and together to identify factors associated with a similar maintained efficacy at Week 52 between patients re-randomized to tralokinumab Q2W or Q4W monotherapy at Week 16. Additionally, the probability of recapturing IGA 0/1 and/or EASI-75 response after relapse was assessed in tralokinumab Q4W patients transferred to the open-label arm.

Results: The two top-ranked predictive factors for maintained response at Week 52 were IGA score at Week 16 (76.1%) and worst daily pruritus numeric rating scale (NRS) <3 at Week 16 (56.5%). Among patients with a stable achievement of both IGA 0/1 and worst daily pruritus NRS <3 from Weeks 12-16 with tralokinumab Q2W, similarly high maintained IGA 0/1 response at Week 52 were seen regardless of dosing regimen beyond Week 16 (Q2W: 72.0%; Q4W: 72.2%). Of patients who relapsed on Q4W, 94.6% recaptured treatment response after returning to Q2W dosing. The immunogenicity potential of tralokinumab was low and patients with positive antidrug antibodies did not show loss of efficacy or higher incidences of adverse events.

Conclusions: These data suggest that Q4W is an effective dosing regimen for most patients who achieved stable disease control, as shown by clear/almost skin and no-to-mild itch over 4 consecutive weeks with tralokinumab Q2W.

Background: SUNSHINE and SUNRISE demonstrated sustained clinical efficacy of secukinumab in patients with moderate-to-severe hidradenitis suppurativa (HS) through 52 weeks. Patients completing the core trials could enter a 4-year extension trial.

Objectives: To evaluate the long-term efficacy, safety/tolerability, and maintenance of clinical response of secukinumab through Week 104 in the extension trial.

Methods: Patients with a HS clinical response (HiSCR) at Week 52 of the core trials (extension trial baseline visit) entered a randomised withdrawal period. HiSCR responders receiving subcutaneous (s.c.) secukinumab 300 mg every 2/4 weeks (SECQ2W/SECQ4W) through Week 52 in the core trials were randomised 2:1 to continue secukinumab (SECQ2W-R-Q2W or SECQ4W-R-Q4W) or receive placebo (SECQ2W-R-PBO or SECQ4W-R-PBO) through Week 104. The primary endpoint was time to loss of response (LOR; newly-defined for this trial) through Week 104 in Week 52 HiSCR responders (SECQ2W-R-Q2W vs. SECQ2W-R-PBO and SECQ4W-R-Q4W vs. SECQ4W-R-PBO). Time to LOR was tested at 1.25% (one-sided) for each comparison (one-sided familywise alpha of 2.5%) through Week 104. If LOR was met, patients could remain in the trial on open-label secukinumab treatment. Additional endpoints included safety and HiSCR.

Results: Overall, 84.3% of patients completing the core trials entered the extension trial; 55.9% were Week 52 HiSCR responders. The primary endpoint was not met for either secukinumab dosing regimen. The estimated risk reduction for LOR was 13% (SECQ2W-R-Q2W vs. SECQ2W-R-PBO; one-sided P=0.250) and 30% (SECQ4W-R-Q4W vs. SECQ4W-R-PBO; one-sided P=0.044). The median time to LOR was numerically longer in secukinumab arms versus placebo (SECQ2W-R-Q2W [283 days; 95% CI: 176, -] vs. SECQ2W-R-PBO [239 days; 95% CI: 120, -]; SECQ4W-R-Q4W [365 days 95% CI: 225, -] vs. SECQ4W-R-PBO [171 days; 95% CI: 113, 337]). In Week 52 HiSCR responders reporting LOR, 43.8% (SECQ2W-R-Q2W), 57.5% (SECQ2W-R-PBO), 39.7% (SECQ4W-R-Q4W) and 34.1% (SECQ4W-R-PBO) were achieving HiSCR at the time of LOR. Overall, the safety of secukinumab was consistent with the core trials.

Conclusions: The primary endpoint of this trial was not met. HiSCR was maintained in many patients at the time of LOR. The safety of secukinumab was consistent with the previously characterised safety profile in the core trials.

Trial registration: Clinicaltrials.gov ID NCT04179175.

Background: A phase III clinical trial in Japanese children aged 6-12 years with atopic dermatitis (AD) and inadequately controlled moderate-to-severe pruritus found that 16 weeks of nemolizumab treatment (30 mg every 4 weeks [Q4W]) was clinically effective and tolerable, with early improvement in pruritus and associated skin signs and a positive impact on patient quality of life (QoL).

Objective: To report the findings from the long-term extension period of the study, and evaluate the efficacy and safety profiles of nemolizumab when administered concomitantly with topical agents over 68 weeks.

Methods: The study included a 16-week, randomized, placebo-controlled, double-blind, parallel-group period during which patients received nemolizumab 30 mg or placebo Q4W; those who completed this period could enter a 52-week, long-term treatment period during which all patients received nemolizumab Q4W. Efficacy endpoints assessed treatment impact on pruritus, AD signs, and QoL. Treatment-emergent adverse events (TEAEs) were tabulated to evaluate long-term safety.

Results: Among the 89 paediatric patients evaluated, efficacy outcome measures showed a tendency towards improvement between weeks 16 and 68, and sustained efficacy during the subsequent follow-up period after treatment cessation. At week 68, among patients who received nemolizumab treatment throughout the study, the mean change from baseline in the 5-level itch score was -1.8 (standard deviation [SD] 0.8), the mean percentage change from baseline in the Average Pruritus Numerical Rating Scale score was -65.9 (SD 25.0), and the mean percentage change from baseline in the Eczema Area and Severity Index score was -77.1 (SD 23.1). Data from the Dermatitis Family Impact questionnaire indicated that the burden of housework on family members was reduced, parent/caregiver fatigue was reduced, and sleep of family members was improved by week 16, with further improvement at week 68. The overall safety profile was similar to that recorded in nemolizumab-treated patients aged ≥13 years, with no late-onset TEAEs observed during long-term treatment.

Conclusions: These data confirm the safety of long-term nemolizumab for paediatric patients with AD, and demonstrate improvements in pruritus, skin symptoms, and both patient and caregiver QoL over 68 weeks of treatment. (Funded by Maruho; Japan Registry of Clinical Trials identifier: jRCT2080225289).