Successful tapering of dupilumab in patients with atopic dermatitis with low disease activity: a large pragmatic daily practice study from the BioDay registry.

BACKGROUND: Limited data are available regarding patient-centred dosing of dupilumab for atopic dermatitis (AD) in daily practice. OBJECTIVES: To evaluate our patient-centred dupilumab dosing regimen in daily practice, to assess prognostic factors for successful tapering and to estimate medication-related cost savings. METHODS: This prospective multicentre study included adult patients with AD, participating in the BioDay registry, treated with dupilumab for ≥ 1.3 years. Interval prolongation was considered in the case of dupilumab standard dose for ≥ 1 year and persistent controlled AD [Eczema Area and Severity Index (EASI) ≤ 7; ≥ 6 months]. Primary endpoints were the mean EASI and Numeric Rating Scale (NRS)-pruritus after the start of tapering. Prognostic factors for successful tapering were analysed with logistic regression and a cost-savings analysis was performed. RESULTS: A total of 595 patients were included, of whom 401 patients [mean EASI 2.5 (SD 2.3); NRS-pruritus of 2.4 (SD 1.9) at the start of tapering] prolonged their dupilumab interval. In 83.3% of these patients tapering was successful; most patients used dupilumab every 3 or 4 weeks (Q3W/Q4W). A significant small increase was observed for EASI (highest mean 3.5) and NRS-pruritus (highest mean 3.2) (P < 0.001); however, scores remained low. Predicting successful tapering showed nonsignificant odds ratios for all incorporated variables. The estimated cost savings was €3 977 033.98 for 401 patients between January 2019 and June 2022. CONCLUSIONS: This study showed successful tapering of dupilumab in 83.3% of patients with AD who attempted tapering, while maintaining controlled disease and with the majority using Q3W/Q4W. Interval prolongation can be beneficial both for the patient and from a socio-economic perspective.

Direct Comparison of Real-world Effectiveness of Biologics for Psoriasis using Absolute and Relative Psoriasis Area and Severity Index Scores in a Prospective Multicentre Cohort.

Real-world evidence, directly comparing the effectiveness of interleukin (IL)17-inhibitors, IL23-inhibitors, tumour necrosis factor alpha (TNF-α)-inhibitors and an IL12/23-inhibitor in psoriasis, is scarce. The aim of this study was to directly compare the first-year effectiveness of biologic therapies for psoriasis, corrected for confounders. This prospective, multicentre cohort study assessed BioCAPTURE data on etanercept, adalimumab, ustekinumab, secukinumab, ixekizumab, and guselkumab in 1,080 treatment episodes of 700 patients with psoriasis. The course of the mean absolute Psoriasis Area and Severity Index (PASI) and the proportion of patients who achieved PASI90/PASI75 were compared using linear mixed models and mixed logistic regression models respectively, corrected for baseline PASI, biologic naivety, and weight. Patients treated with adalimumab, ustekinumab, secukinumab, ixekizumab, or guselkumab all had a significantly lower mean PASI after 12 months compared with etanercept, and significantly higher overall odds of reaching PASI90 than those treated with etanercept. Patients treated with ixekizumab or guselkumab also had higher probabilities of reaching PASI90 than adalimumab, ustekinumab, and secukinumab. Relative to randomized controlled trials, the proportions of patients who reached PASI90/75 were lower in this real-world study.

Nail Sarcoidosis Presenting with Longitudinal Erythronychia.

A 37-year-old woman presented with progressive longitudinal erythronychia and onychorrhexis of the toenails. She had a history of sarcoidosis of the lung and nose, which was silent without treatment at the time of presentation. Histopathological examination of a nail matrix biopsy revealed granulomas with palisading histiocytes in the connective tissue and a lymphocytic infiltrate in and around the granulomas without necrosis. Based on the clinical presentation, medical history, and histopathological examination, the diagnosis of nail sarcoidosis was made. Treatment with triamcinolone acetonide 40 mg/mL resulted in the disappearance of the onychorrhexis and a significant improvement of erythronychia. To our knowledge, a clinical presentation with longitudinal erythronychia as seen in our patient has not been previously described. Bone involvement of the underlying distal phalanges and systemic involvement can be paucisymptomatic but are present in most patients with sarcoidosis of the nails. Nail and bone involvement are both regarded as features of chronic and systemic sarcoidosis. Screening for bone and systemic involvement should be performed in all patients with nail sarcoidosis, as this may influence decisions on treatment and follow-up. Therefore, it is important to recognize longitudinal erythronychia as a possible clinical sign of nail sarcoidosis.

[A refugee with inguinal lymfadenopathy and skin lesions]. / Een vluchteling met lymfadenopathie en huiduitslag.

We present a 30-years-old man with lymphadenopathy and itchy skin lesions. One lymphoblast and atypical lymphocytes were found in the peripheral blood. Histopathologic examination of a skin punch biopsy revealed scabies. Lymphadenopathy is normally only seen in patients with widespread long-lasting scabies crustosa. However, this case illustrates that scabies should also be included in the differential diagnosis of patients with lymphadenopathy and only a few itchy skin lesions.

Extent and consequences of antibody formation against adalimumab in patients with psoriasis: one-year follow-up.

IMPORTANCE: In a previously reported cohort of 29 patients with plaque-type psoriasis followed up for 24 weeks, clinically relevant antidrug antibody (ADA) to adalimumab was frequently found. Long-term data were lacking. We now present the extension of this study: 80 patients followed up for 1 year. OBJECTIVES: To assess the extent of ADA and its clinical consequences after 24 weeks of adalimumab treatment for psoriasis in a cohort of 80 patients. DESIGN, SETTING, AND PARTICIPANTS: A multicenter cohort study, performed in the outpatient dermatology clinic of 2 academic hospitals, included 80 sequential patients receiving adalimumab therapy for plaque-type psoriasis and had a follow-up of 1 year. Outcome assessors were not aware of the presence of antibodies to adalimumab or the adalimumab serum concentration when assessing patients' Psoriasis Area and Severity Index (PASI), and personnel analyzing serum samples were blinded to patients' PASI. INTERVENTIONS: For 80 patients treated with adalimumab for psoriasis, disease severity (PASI) was assessed, blood samples were collected, and adalimumab and ADA concentrations was determined at baseline and at weeks 12, 24, and 52. MAIN OUTCOMES AND MEASURES: Patient PASI and adalimumab and ADA concentrations. RESULTS: Antidrug antibody formed in 49% of patients, before week 24 in 90% of them. Adalimumab and ADA concentrations, clinical response and ADA concentration, and adalimumab concentration and clinical response had correlations of -0.872, -0.606, and 0.519, respectively. The adalimumab dose interval was shortened because of lack of efficacy in 15 patients, 7 with and 8 without ADA; improvement in responder status occurred in 1 of 7 and 4 of 8, respectively. CONCLUSIONS AND RELEVANCE: Patients with no ADA formation in the first 24 weeks of treatment have little chance of it in the following 24 weeks. The presence of ADA is strongly correlated with adalimumab concentration and greatly influences clinical response. If ADA is present, dose interval shortening is less useful.

Results of three analytical approaches on long-term efficacy of etanercept for psoriasis in daily practice.

BACKGROUND: A problem encountered when analyzing long-term efficacy is that the number of patients in follow-up decreases with time for different reasons. The method used to account for missing observations for the therapy under analysis has a great influence on the inference of efficacy. OBJECTIVE: To describe the long-term efficacy of etanercept for psoriasis in daily practice using 3 analytical approaches. METHODS: Prospective data from a cohort of patients with psoriasis treated with etanercept for at least 24 weeks were analyzed using 3 analytical approaches: as treated analysis, intention-to-treat analysis (ITT) with last observation carried forward (LOCF) and intention-to-treat analysis with modified nonresponder imputation (modified NRI). RESULTS: One hundred thirty-one patients were treated with etanercept during 134 treatment episodes with a mean treatment duration of 2.7 years. The maximum follow-up was 6.0 years. The methodological approach chosen had a great influence. Psoriasis Area and Severity Index (PASI) 75 response rates varied from 60% in the as-treated approach to 34% in LOCF and to 29% in modified NRI at week 264. LIMITATIONS: All analytical methods applied have limitations. Other outcome measures could be used to overcome the bias introduced by each method of analysis, such as drug survival. CONCLUSIONS: The methodological approach chosen to analyze long-term efficacy data has a great influence on the inferences that may be drawn regarding the degree of efficacy. Therefore we support the use of different methods to present long-term efficacy data.

Effectiveness of adalimumab dose escalation, combination therapy of adalimumab with methotrexate, or both in patients with psoriasis in daily practice.

BACKGROUND: To increase effectiveness of standard adalimumab treatment 40 mg every other week (EOW) for patients with psoriasis, dose escalation to 40 mg every week or addition of methotrexate (MTX) are possible strategies. METHODS: Daily practice data about adalimumab treatment were extracted from a prospective observational cohort. We analyzed all patients with insufficient efficacy of adalimumab EOW who received 1) adalimumab dose escalation, 2) addition of MTX to adalimumab EOW, or 3) both. Effectiveness was analyzed after 12 and 24 weeks using PASI50, PASI75, and mean differences in PASI. RESULTS: Forty-seven treatment episodes (TE) of adalimumab dose escalations, 11 of MTX addition and six combinations were analyzed. After a first episode of adalimumab dose escalation, 25% and 35% achieved PASI50 after 12 and 24 weeks, respectively. After MTX introduction to adalimumab EOW, 9% and 18% achieved PASI50 after 12 and 24 weeks, respectively. No related serious adverse events were reported. CONCLUSIONS: Twenty-five percent of first TE with adalimumab dose escalation induced a PASI50 response after 12 weeks and 35% after 24 weeks. Addition of MTX to adalimumab EOW resulted in PASI50 in 9% after 12 weeks and 18% after 24 weeks. Defining patient-groups that will benefit from these interventions is important.