Drug Survival, Safety, and Effectiveness of Biologics in Older Patients with Psoriasis: A Comparison with Younger Patients-A BioCAPTURE Registry Study.

BACKGROUND: Psoriasis is a common inflammatory disease in any age group, but also in older patients (≥ 65 years of age). Since older patients are often excluded from clinical trials, limited data specifically on this growing population are available, e.g. regarding the safety and performance of biological treatment. AIMS: We aimed to give insight into this specific population by comparing the drug survival and safety of biologics in older patients with that in younger patients. METHODS: In this real-world observational study, data from 3 academic and 15 non-academic centers in The Netherlands were extracted from the prospective BioCAPTURE registry. Biologics included in this study were tumor necrosis factor (TNF)-α, interleukin (IL)-17, IL-12/23, and IL-23 inhibitors. Patients were divided into two age groups: ≥ 65 years and < 65 years. The Charlson Comorbidity Index (CCI) was used to measure comorbid disease status, and all adverse events (AEs) that led to treatment discontinuation were classified according to the Medical Dictionary for Regulatory Activities (MedDRA) classification. All AEs that led to treatment discontinuation were studied to check whether they could be classified as serious AEs (SAEs). Kaplan-Meier survival curves for overall 5-year drug survival and split according to reasons of discontinuation (ineffectiveness or AEs) were constructed. Cox regression models were used to correct for possible confounders and to investigate associations with drug survival in both age groups separately. Psoriasis Area and Severity Index (PASI) scores during the first 2 years of treatment and at the time of treatment discontinuation were assessed and compared between age groups. RESULTS: A total of 890 patients were included, of whom 102 (11.4%) were aged ≥ 65 years. Body mass index, sex, and distribution of biologic classes (e.g. TNFα, IL12/23) were not significantly different between the two age groups. A significantly higher CCI score was found in older patients, indicative of more comorbidity (p < 0.001). The 5-year ineffectiveness-related drug survival was lower for older patients (44.5% vs. 60.5%; p = 0.006), and the 5-year overall (≥ 65 years: 32.4% vs. < 65 years: 42.1%; p = 0.144) and AE-related (≥ 65 years: 82.1% vs. < 65 years: 79.5%; p = 0.913) drug survival was comparable between age groups. Of all AEs (n = 155) that led to discontinuation, 16 (10.3%) were reported as SAEs but these only occurred in younger patients. After correcting for confounders, the same trends were observed in the drug survival outcomes. Linear regression analyses on PASI scores showed no statistical differences at 6, 12, 18, and 24 months of treatment between age groups. CONCLUSIONS: This study in a substantial, well-defined, prospective cohort provides further support that the use of biologics in older patients seems well-tolerated and effective. Biologic discontinuation due to AEs did not occur more frequently in older patients. Older patients discontinued biologic treatment more often due to ineffectiveness, although no clear difference in PASI scores was observed. More real-world studies on physician- and patient-related factors in older patients are warranted.

Biopsy outperforms reflectance confocal microscopy in diagnosing and subtyping basal cell carcinoma: results and experiences from a randomized controlled multicentre trial.

BACKGROUND: Reflectance confocal microscopy (RCM) is a noninvasive method for skin assessment, allowing entire lesion evaluation up to the papillary dermis. RCM is a potentially attractive alternative to punch biopsy (PB) in basal cell carcinoma (BCC). OBJECTIVES: To determine the diagnostic accuracy of RCM vs. PB in diagnosing and subtyping BCC, and to study patient satisfaction and preferences. METHODS: Patients with a clinically suspected primary BCC were randomized between RCM and biopsy. Conventional surgical excision or follow-up were used as reference. Sensitivity and specificity for BCC diagnosis and subtyping were calculated for both methods. BCC subtype was stratified based on clinical relevance: aggressive (infiltrative/micronodular) vs. nonaggressive (superficial/nodular) histopathological subtype and superficial vs. nonsuperficial BCC. Data on patient satisfaction and preferences were collected using a questionnaire and a contingent valuation method. RESULTS: Sensitivity for BCC diagnosis was high and similar for both methods (RCM 99·0% vs. biopsy 99·0%; P = 1·0). Specificity for BCC diagnosis was lower for RCM (59·1% vs. 100·0%; P < 0·001). Sensitivity for aggressive BCC subtypes was lower for RCM (33·3% vs. 77·3%; P = 0·003). Sensitivity for nonsuperficial BCC was not significantly different (RCM 88·9% vs. biopsy 91·0%; P = 0·724). Patient satisfaction and preferences were good and highly comparable for both methods. CONCLUSIONS: Biopsy outperforms RCM in diagnosing and subtyping clinically suspected primary BCC. This outcome does not support routine clinical implementation of RCM, as a replacement for PBs in this patient group.

Frailty screening in dermato-oncology practice: a modified Delphi study and a systematic review of the literature.

BACKGROUND: Appropriate management and prevention of both under- and overtreatment in older skin cancer patients can be challenging. It could be helpful to incorporate frailty screening in dermato-oncology care, since frailty is associated with adverse health outcomes. OBJECTIVES: This study aimed to identify and prioritize the requirements a frailty screening tool (FST) should fulfil in dermato-oncology practice and to select the best existing FST(s) for this purpose. METHODS: A modified two-round Delphi procedure was performed among 50 Italian and Dutch specialists and patients to review and prioritize a list of potential FST requirements, using a 5-point Likert scale. Consensus was defined as a mean score of ≥4.0. A systematic literature search was performed to identify existing multidomain FSTs, which were then assessed on the requirements resulting from the modified Delphi procedure. RESULTS: Consensus was achieved on evaluation of comorbidities (4.3 ± 0.7), polypharmacy (4.0 ± 0.9) and cognition (4.1 ± 0.8). The FST should have appropriate measurement properties (4.0 ± 1.0), be quickly executed (4.2 ± 0.7), clinically relevant (4.3 ± 0.7), and both easily understandable (4.1 ± 1.2) and interpretable (4.3 ± 0.7). Of the 26 identified FSTs, four evaluated the content-related domains: the Geriatric-8 (G8), the modified Geriatric-8 (mG8), the Groningen Frailty Indicator (GFI) and the Senior Adult Oncology Program 2 (SAOP2) screening tool. Of these, the G8 was the most extensively studied FST, with the best psychometric properties and execution within 5 min. CONCLUSIONS: The G8 appears the most suitable FST for assessing frailty in older adults with skin cancer, although clinical studies assessing its use in a dermato-oncology population are needed to further assess whether or not frailty in this particular patient group is associated with relevant outcomes (e.g. complications and mortality), as seen in previous studies in other medical fields.

The effect of a dermato-oncological training programme on the diagnostic skills and quality of referrals for suspicious skin lesions by general practitioners.

BACKGROUND: The rising incidence rates of skin cancer (SC) lead to an enormous burden on healthcare systems. General practitioners (GPs) might play an important part in SC care, but research has shown poor clinical recognition of SC, leading to a high rate of potentially unnecessary referrals. OBJECTIVES: The aim of this study was to evaluate if a dermato-oncological training programme (DOTP) for GPs improved their diagnostic skills and quality of referrals. METHODS: Out of 194 GPs in the Nijmegen area, 83 (42·8%) followed a DOTP on SC. Referrals from both a trained cohort (TC) and two cohorts of untrained GPs [untrained present cohort (UPC) and untrained historical cohort (UHC)] were included. Data on diagnostic skills, quality of referrals and the number of potentially unnecessary referrals were evaluated. RESULTS: A total number of 1662 referrals were analysed. The referral diagnosis was correct more often in the TC (70·3%) compared with the UPC (56·2%; P < 0·001) and the UHC (51·6%; P < 0·001). Furthermore, the TC also provided a better lesion description, mentioned a diagnosis more often in their referral letters and more often performed diagnostics before referral. In addition, fewer potentially unnecessary referrals were identified in the TC compared with the UPC (62·7% vs. 73·7%; P < 0·001) and the UHC (75·2%; P < 0·001). CONCLUSIONS: GPs who followed a DOTP had better diagnostic skills and quality of referrals than untrained GPs, leading to fewer potentially unnecessary referrals. This might enhance a more efficient use of the limited capacity in secondary dermatological care and consequently lead to lower healthcare costs.

Improving the applicability of guidelines on nonmelanoma skin cancer in frail older adults: a multidisciplinary expert consensus and systematic review of current guidelines.

BACKGROUND: Balancing treatment decisions in frail older adults with nonmelanoma skin cancer (NMSC) can be challenging. Clinical practice guidelines (CPGs) could provide assistance. OBJECTIVES: To collect and prioritize items related to frail older adults with NMSC for integration into CPGs and to assess the current extent of this integration. METHODS: Items were collected and prioritized by a multidisciplinary working group (29 members) using a modified Delphi procedure and a five-point Likert scale. To assess current integration of these items in CPGs, a systematic review was subsequently performed by two independent reviewers using five medical databases (PubMed, Embase, Cochrane Library, SUMsearch and Trip Database), websites of guideline developers/databases, and (inter)national dermatological societies. RESULTS: Prioritization of a final 13-item list showed that 'limited life expectancy' (4·5 ± 0·9) and 'treatment goals other than cure' (4·4 ± 0·7) were most desired to be integrated into CPGs; both were included in six (46%) of the CPGs found (n = 13). Attention to 'tumour characteristics' and 'comorbidities' were included in CPGs most often (100% and 77%, respectively). CONCLUSIONS: More attention to items related to frail older adults in NMSC CPGs is broadly desired, but CPG integration of these items is currently limited. More integration might stimulate more holistic, personalized and patient-centred care in frail older adults.