Introduction
Dupilumab has recently been approved for the treatment of moderate to severe atopic dermatitis (AD) in adults. Daily practice data on dupilumab treatment are scarce.
Objective
To study ...the effect of 16‐week treatment with dupilumab on clinical response and serum biomarkers in adult patients with moderate‐severe AD in daily practice.
Methods
Data were extracted from the BioDay registry, a prospective multicenter registry. Sixteen‐week clinical effectiveness of dupilumab was expressed as number of patients achieving EASI‐50 (Eczema Area and Severity Index) or EASI‐75, as well as patient‐reported outcomes measures (Patient‐Oriented Eczema Measure, Dermatology Life Quality Index, Numeric Rating Scale pruritus). Twenty‐one biomarkers were measured in patients treated with dupilumab without concomitant use of oral immunosuppressive drugs at five different time points (baseline, 4, 8, 12, and 16 weeks).
Results
In total, 138 patients treated with dupilumab in daily practice were included. This cohort consisted of patients with very difficult‐to‐treat AD, including 84 (61%) patients who failed treatment on ≥2 immunosuppressive drugs. At week 16, the mean percent change in EASI score was 73%. The EASI‐50 and EASI‐75 were achieved by 114 (86%) and 82 (62%) patients after 16 weeks of treatment. The most reported side effect was conjunctivitis, occurring in 47 (34%) patients. During dupilumab treatment, disease severity‐related serum biomarkers (TARC, PARC, periostin, and IL‐22), eotaxin‐1, and eotaxin‐3 significantly decreased.
Conclusion
Treatment with dupilumab significantly improved disease severity and decreased severity‐related serum biomarkers in patients with very difficult‐to‐treat AD in a daily practice setting.
This study evaluated the clinical effectiveness and safety of 16‐weeks of dupilumab treatment in adults with AD. Dupilumab treatment significantly suppressed disease severity‐related serum biomarkers and eosinophil chemokines. By the end of the treatment, the EASI‐50 and EASI‐75 was achieved by 86% and 62% of patients, respectively.
Abbreviations: AD: Atopic dermatitis; DLQI: Dermatology life quality index; EASI: Eczema area and severity index; IGA: Investigators global assessment; NRS: Numeric rating scale; PARC: Pulmonary and activation‐regulated chemokine; POEM: Patient‐oriented eczema measure; TARC: Thymus‐ and activation‐regulated chemokine
Background
The hands are a common predilection site of atopic dermatitis (AD). Dupilumab is licensed for the treatment of AD but not for chronic hand eczema (CHE), while CHE is challenging to treat.
...Objectives
To evaluate the long‐term effect of dupilumab on hand eczema (HE) in patients with AD from the BioDay Registry.
Methods
A prospective observational study of adult patients with HE, treated for AD with dupilumab. Patients with a HE severity of at least moderate at baseline were considered for analysis. Patients with other concomitantly systemic immunosuppressive treatments were excluded. Clinical effectiveness on HE severity, using the Hand Eczema Severity Index (HECSI) and photographic guide, and health‐related quality of life, using the Quality of Life in Hand Eczema Questionnaire (QOLHEQ), were evaluated.
Results
A total of 72 patients were included. HECSI‐75 was achieved by 54/62 patients (87.1%) and HECSI‐90 by 39/72 (62.9%) at 52 weeks. Based on the photographic guide, 56/62 patients (90.3%) achieved the endpoint of ‘clear’ or ‘almost clear’. Mean QOLHEQ reduction was −63.5% (95% confidence interval −38.23 to −27.41). There was no difference in response between HE subtypes.
Conclusions
The results from this study hold promise for dupilumab to be a suitable treatment option for isolated CHE.
Dupilumab for atopic hand eczema.
Dupilumab is licensed for the treatment of atopic dermatitis (AD) but not for chronic hand eczema (CHE), while CHE is challenging to treat.
Dupilumab gave long‐term reduction of hand eczema severity and long‐term improvement of hand eczema‐related quality of life in patients with AD and concomitant moderate to very severe hand eczema.
The results from this study hold promise for dupilumab to be a suitable treatment option for isolated CHE.
Background
At present, no real‐world studies are available on different dupilumab dosing regimens in controlled atopic dermatitis (AD). The aim of this study was to clinically evaluate a ...patient‐centered dupilumab dosing regimen in patients with controlled AD and to relate this to serum drug levels and serum biomarkers.
Methods
Ninety adult AD patients from the prospective BioDay registry were included based on their dupilumab administration interval according to a predefined patient‐centered dosing regimen. Group A (n = 30) did not fulfill the criteria for interval prolongation and continued using the standard dupilumab dosage (300 mg/2 weeks), group B (n = 30) prolonged dupilumab interval with 50% (300 mg/4 weeks), and group C (n = 30) prolonged dupilumab interval with 66%–75% (300 mg/6–8 weeks). AD severity score, patient‐reported outcomes, serum dupilumab levels, and serum biomarkers were analyzed over time.
Results
Disease severity scores did not significantly change over time during the tapering period in any of the groups. In groups B and C, the Numeric Rating Scale (NRS)‐pruritus temporarily significantly increased after interval prolongation but remained low (median NRS‐pruritus≤4). Median dupilumab levels remained stable in group A (standard dosage), but significantly decreased in groups B and C (24.1 mg/L (IQR = 17.1–45.6); 12.5 mg/L (IQR = 1.7–22.3)) compared with the levels during the standard dosage (88.2 mg/L IQR = 67.1–123.0, p < .001). Disease severity biomarker levels (CCL17/CCL18) remained low in all study groups during the whole observation period.
Conclusions
This study showed that dose reduction was successful in a subgroup of patients with controlled AD by using a patient‐centered dosing regimen. These patients showed stable low disease activity and low severity biomarkers over time.
Dose reduction was successful in a subgroup of controlled AD patients by using a patient‐centered dupilumab dosing regimen. Despite significantly lower dupilumab levels, the EASI‐score and disease severity biomarkers (TARC/CCL17 and PARC/CCL18) in groups B (Q4W) and C (Q6W/Q8W) remained low and stable. These findings are the first step toward personalized dupilumab treatment for controlled AD patients in clinical practice.Abbreviations: AD, atopic dermatitis; EASI, eczema area and severity index; PARC (CCL18), pulmonary and activation‐regulated chemokine; PROMs, patient‐reported outcome measures; Q2W, every two weeks; Q4W, every four weeks; Q6W, every six weeks; Q8W, every eight weeks; TARC (CCL17), thymus and activation‐regulated chemokine
Aims
In immune‐mediated inflammatory diseases (IMIDs), early symptom control is a key therapeutic goal. Methotrexate (MTX) is the first‐line treatment across IMIDs. However, MTX is underutilized and ...suboptimally dosed, partly due to the inability of making individualized treatment decisions through therapeutic drug monitoring (TDM). To implement TDM in clinical practice, establishing a relationship between drug concentration and disease activity is paramount. In this meta‐analysis, we investigated the relationship between concentrations of MTX polyglutamates (MTX‐PG) in erythrocytes and efficacy as well as toxicity across IMIDs.
Methods
Studies analysing MTX‐PG in relation to disease activity and/or toxicity were included for inflammatory arthritis (rheumatoid RA and juvenile idiopathic arthritis JIA), inflammatory bowel disease (Crohn's and ulcerative colitis) and dermatitis (psoriasis and atopic dermatitis). Meta‐analyses were performed resulting in several summary effect measures: regression coefficient (β), correlation coefficient and mean difference (of MTX‐PG in responders vs. nonresponders) for IMIDs separately and collectively.
Results
Twenty‐five studies were included. In RA and JIA, higher MTX‐PG was significantly associated with lower disease activity at 3 months (β: −0.002; 95% confidence interval CI: −0.004 to −0.001) and after 4 months of MTX use (β: −0.003; 95% CI: −0.005 to −0.002). Similarly, higher MTX‐PG correlated with lower disease activity in psoriasis (R: −0.82; 95% CI: −0.976 to −0.102). Higher MTX‐PG was observed in RA, JIA and psoriasis responders (mean difference: 5.2 nmol/L MTX‐PGtotal; P < .01).
Conclusion
We showed that higher concentrations of erythrocyte MTX‐PG were associated with lower disease activity in RA, JIA and psoriasis. These findings are an important step towards implementation of TDM for MTX treatment across IMIDs.
Systemic treatment options for chronic hand eczema are limited. Dupilumab is used in atopic dermatitis (AD) but is not licensed for (isolated) hand eczema. In this observational prospective study we ...aimed to determine the response of hand eczema to dupilumab in patients with AD. Adult patients with hand eczema and AD received dupilumab s.c. at a 600 mg loading dose, followed by 300 mg every 2 weeks. Primary outcome was a minimum improvement of 75% on the Hand Eczema Severity Index after 16 weeks (HECSI‐75). Secondary outcomes were severity, measured using the Photographic guide; quality of life improvement as patient‐reported outcome, measured using the Dermatology Life Quality Index (DLQI); and AD severity, measured using the Eczema Area and Severity Index (EASI). Forty‐seven patients were included (32 males; mean age, 45 years). HECSI‐75 was achieved by 28 (60%). Mean HECSI score reduction was 49.2 points (range, 0–164; 95% within‐subject confidence interval, 46.4–52.0), which was already significantly decreased after 4 weeks (P < 0.001). DLQI score mean improvement was 8.8 points (standard deviation SD, 6.0) or 70.0% decrease (SD, 26.4) (P < 0.001). Eighteen patients (38%) were classified as responders on the Photographic guide. There was no difference in response between chronic fissured and recurrent vesicular clinical subtypes. Similar percentages of patients achieving EASI‐75 and HECSI‐75 were seen after 16 weeks. In conclusion, this study shows a favorable response of hand eczema to dupilumab in patients with AD. This raises the question whether a response will also be seen in isolated hand eczema.
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