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
Context and Objective: GH therapy increases growth and adult height in Turner syndrome (TS). The benefit to risk ratio of adding the weak androgen oxandrolone (Ox) to GH is unclear.
Design and ...Participants: A randomized, placebo-controlled, double-blind, dose-response study was performed in 10 centers in The Netherlands. One hundred thirty-three patients with TS were included in age group 1 (2–7.99 yr), 2 (8–11.99 yr), or 3 (12–15.99 yr). Patients were treated with GH (1.33 mg/m2 · d) from baseline, combined with placebo (Pl) or Ox in low (0.03 mg/kg · d) or conventional (0.06 mg/kg · d) dose from the age of 8 yr and estrogens from the age of 12 yr. Adult height gain (adult height minus predicted adult height) and safety parameters were systematically assessed.
Results: Compared with GH+Pl, GH+Ox 0.03 increased adult height gain in the intention-to-treat analysis (mean ± sd, 9.5 ± 4.7 vs. 7.2 ± 4.0 cm, P = 0.02) and per-protocol analysis (9.8 ± 4.9 vs. 6.8 ± 4.4 cm, P = 0.02). Partly due to accelerated bone maturation (P < 0.001), adult height gain on GH+Ox 0.06 was not significantly different from that on GH+Pl (8.3 ± 4.7 vs. 7.2 ± 4.0 cm, P = 0.3). Breast development was slower on GH+Ox (GH+Ox 0.03, P = 0.02; GH+Ox 0.06, P = 0.05), and more girls reported virilization on GH+Ox 0.06 than on GH+Pl (P < 0.001).
Conclusions: In GH-treated girls with TS, we discourage the use of the conventional Ox dosage (0.06 mg/kg · d) because of its low benefit to risk ratio. The addition of Ox 0.03 mg/kg · d modestly increases adult height gain and has a fairly good safety profile, except for some deceleration of breast development.
In GH-treated girls with Turner syndrome, 0.03 mg/kg/d of oxandrolone modestly increases adult height gain and has a fairly good safety profile.
Objective
Autologous stem cell transplantation (ASCT) induces long‐term drug‐free disease remission in patients with juvenile idiopathic arthritis. This study was undertaken to further unravel the ...immunologic mechanisms underlying ASCT by using a mouse model of proteoglycan‐induced arthritis (PGIA).
Methods
For initiation of PGIA, BALB/c mice received 2 intraperitoneal injections of human PG in a synthetic adjuvant on days 0 and 21. Five weeks after the first immunization, the mice were exposed to total body irradiation (7.5 Gy) and received (un)manipulated bone marrow (BM) grafts from mice with PGIA. Clinical scores, T cell reconstitution, (antigen‐specific) T cell cytokine production, and intracellular cytokine expression were determined following autologous BM transplantation (ABMT).
Results
ABMT resulted in amelioration and stabilization of arthritis scores. BM grafts containing T cells and T cell–depleted grafts provided the same clinical benefit, with similar reductions in PG‐induced T cell proliferation and the number of PG‐specific autoantibodies. In vivo reexposure to PG did not exacerbate disease. Following ABMT, basal levels of disease‐associated proinflammatory cytokines (interferon‐γ IFNγ, interleukin‐17 IL‐17, and tumor necrosis factor α TNFα) were reduced. In addition, restimulation of T cells with PG induced a strong reduction in disease‐associated proinflammatory cytokine production. Finally, although the remaining host T cells displayed a proinflammatory phenotype following ABMT, IFNγ, IL‐17, and TNFα production by the newly reconstituted donor‐derived T cells was significantly lower.
Conclusion
Taken together, our data suggest that ABMT restores immune tolerance by renewal and modulation of the Teff cell compartment, leading to a strong reduction in proinflammatory (self antigen–specific) T cell cytokine production.
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