Efficacy and Safety of HLX03, an Adalimumab Biosimilar, in Patients with Moderate-to-Severe Plaque Psoriasis: A Randomized, Double-Blind, Phase III Study.

INTRODUCTION: Adalimumab has been used successfully in the treatment of psoriasis. The objective of the study is to compare the efficacy, safety, and immunogenicity between HLX03, an adalimumab biosimilar, and adalimumab in Chinese patients with moderate-to-severe plaque psoriasis. METHODS: In this double-blind, active-controlled, parallel-group study, 262 patients with moderate-to-severe plaque psoriasis were randomized (1:1) to receive HLX03 or adalimumab (80 mg at week 1, 40 mg at week 2, and then 40 mg every 2 weeks) for 48 weeks. The primary endpoint was improvement in Psoriasis Area and Severity Index (PASI) score at week 16 comparing to baseline. Equivalence was demonstrated if 95% confidence interval (CI) of the between group difference fell within the equivalence margins of ± 15%. Other efficacy endpoints, safety and immunogenicity were also evaluated. RESULTS: In the full analysis set, PASI improvements at week 16 was 83.5% (n = 131) in the HLX03 group and 82.0% (n = 130) in the adalimumab group, with a least-square-mean difference of 1.5% (95% CI - 3.9% to 6.8%). There were no significant between-group differences in all secondary efficacy analyses including proportion of patients achieving ≥ 75% improvement from baseline PASI (PASI 75), physician global assessment (PGA) 0/1 (clear or almost clear) and change in dermatology life quality index (DLQI) score. The incidences of adverse events and the proportion of patients with antidrug antibodies were also comparable between the two treatment groups. CONCLUSION: HLX03 demonstrated equivalent efficacy, similar safety and immunogenicity to reference adalimumab, supporting its development as an alternative treatment for patients with plaque psoriasis in China. CLINICAL TRIAL REGISTRATION: Chinadrugtrials.org.cn, CTR20171123 (November 27, 2017); ClinicalTrials.gov, NCT03316781 (October 20, 2017).

Plaque psoriasis is a chronic, autoimmune, inflammatory skin disease associated with significant morbidity and reduced quality of life. In China, the prevalence of plaque psoriasis increased four-fold between 1987 and 2012. Adalimumab is a biologic antibody used to treat plaque psoriasis globally. However, high treatment costs remain as a significant barrier to adalimumab therapy. Therefore, HLX03 has been developed as an adalimumab (Humira^®) biosimilar, which is almost identical to the licensed reference adalimumab, but less expensive and more accessible to patients. In this randomized clinical trial, the efficacy (ability of a drug to produce the desired treatment effects), safety, and immunogenicity (ability of a drug to induce immune response which would affect its efficacy and safety) of HLX03 were compared with the reference adalimumab in Chinese patients with moderate-to-severe plaque psoriasis. Efficacy was evaluated by comparing the changes in severity and extent of disease using Psoriasis Area and Severity Index score between treatment initiation and week 16. Safety was monitored by adverse events, laboratory tests and vital signs. Immunogenicity was assessed by the incidence of antidrug antibodies. Among the 262 randomized patients, 131 received HLX03 and 130 received adalimumab. Both groups reported similar improvements in Psoriasis Area and Severity Index scores (between-group difference fell within the prespecified equivalence margins), and also in other efficacy evaluations. Additionally, the two treatment groups showed similar safety and immunogenicity profiles. In summary, HLX03 demonstrated equivalent efficacy to adalimumab, validating it as an alternative treatment for patients with plaque psoriasis in China.

Secukinumab demonstrates high efficacy and a favorable safety profile over 52 weeks in Chinese patients with moderate to severe plaque psoriasis.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease, affecting about 0.6% of the Chinese population. Many patients are not well controlled by conventional treatments, thus there is need for new treatment regimens. In this study, we assessed the efficacy and safety of secukinumab in Chinese patients with moderate to severe plaque psoriasis. METHODS: This study was a 52-week, multicentre, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 trial. A sub-population of study participants (≥18 years) of Chinese ethnicity were randomized to receive subcutaneous injections of 300 or 150 mg secukinumab, or placebo. The co-primary endpoints were psoriasis area severity index (PASI) 75 and Investigator's Global Assessment (IGA) 0/1 at Week 12. RESULTS: A total of 441 Chinese patients were enrolled in this study. Co-primary outcomes were achieved; 300 and 150 mg secukinumab were superior to placebo as shown in the proportion of patients that achieved PASI 75 (97.7% and 87.2% vs. 3.7%, respectively; P < 0.001), and IGA 0/1 (82.3% and 69.7% vs. 2.7%; P < 0.001) at Week 12. Treatment efficacy was maintained until Week 52. There was no increase in overall adverse events with secukinumab relative to placebo throughout the 52-week period. CONCLUSION: Secukinumab is highly effective and well tolerated in Chinese patients with moderate to severe plaque psoriasis. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03066609; https://clinicaltrials.gov/ct2/show/record/NCT03066609.

Sublingual immunotherapy of atopic dermatitis in mite-sensitized patients: a multi-centre, randomized, double-blind, placebo-controlled study.

Allergen-specific immunotherapy is widely used for allergic rhinitis and asthma treatment worldwide. This study explored the efficacy and safety of sublingual immunotherapy (SLIT) with the extracts of Dermatophagoides Farinae (D. farinae Drops) on house dust mites (HDM)-induced atopic dermatitis (AD). 239 patients with HDM-induced AD were recruited and exposure to a multi-centre, randomized, double-blind, and placebo-controlled clinical trials for 36 weeks, which were randomly divided into placebo and sublingual D. farinae Drops groups (high-dose, medium-dose and low-dose), respectively. Statistical analysis was performed in three groups: Full Analysis Set, Per Protocol Set and Safety Set. 48 cases have withdrawn from the study before the end of study. As primary outcomes, significant decreases in scoring atopic dermatitis and total medication score were showed in medium-dose and high-dose D. farinae Drops groups. In the sixth visit, the skin lesion area showed a statistically significant difference between high-dose/medium-dose D. farinae Drops group and placebo group (p < .05). Most adverse events are slight, and no life-threatening adverse drug reaction happened. Our research demonstrates the beneficial effect of SLIT with high or medium dose D. farinae Drops on AD, and the treatment was well tolerated.

Graft-versus-host-disease after kidney transplantation: A case report and literature review.

INTRODUCTION: Acute graft-versus-host-disease (GVHD) in kidney recipients is extremely rare. Knowledge about its clinical manifestations, diagnosis, treatment, and prognosis is limited and needs to be increased. CLINICAL FINDINGS: One male kidney transplant recipient developed diarrhea and suffered kidney function damage. Primarily diagnosed with acute rejection, he was given methylprednisolone (MP) bolus treatment. Meanwhile, intravenous immunoglobulin (IVIG) and decreased immunosuppressive agents were applied for the corresponding infection. During the treatment, skin rashes occurred over his whole body. Biopsies were then taken. The pathology of the kidney graft showed no rejection, while the skin pathology revealed typical GVHD. Furthermore, fluorescence in situ hybridization proved the presence of donor-derived cells in the skin lesions, and infiltrating cytotoxic T cells and NK cells were identified in the rash. OUTCOME: Based on the clinical presentations, pathological findings, and chimerism detection, GVHD after kidney transplantation was confirmed as the final diagnosis. The recipient responded well to treatment. His kidney function recovered, and the skin lesions were completely resolved. He has been followed for 1 year without any further episodes. CONCLUSION: GVHD after kidney transplantation has its own characteristics. In the presence of a highly immunocompromised state, diarrhea and rashes, a diagnosis of GVHD needs to be considered. Kidney function impairment may be involved. Pathological changes and detection of chimerism and immunocyte infiltration are required for diagnosis. MP bolus, IVIG, and decreased immunosuppression could be beneficial to the clinical outcome. Kidney recipients have a prognosis superior to recipients of organs bearing large numbers of lymphocytes.

Multicenter randomized study of inosine pranobex versus acyclovir in the treatment of recurrent herpes labialis and recurrent herpes genitalis in Chinese patients.

The objective of the study is to evaluate the efficacy and safety of oral inosine pranobex as compared with acyclovir in the treatment of recurrent herpes labialis (RHL) and recurrent herpes genitalis (RHG). A multicenter double-blind, double-dummy, randomized, controlled, parallel group trial was conducted in 144 patients with RHL and 144 RHG. Patients were assigned to treatment in one of two groups: (i) inosine pranobex group (active inosine pranobex, 1 g four times daily, and acyclovir placebo); or (ii) acyclovir group (active acyclovir, 200 mg five times daily, and inosine pranobex placebo). The total symptom score (TSS) of patients with RHL did not differ in the inosine pranobex and acyclovir group on the 3rd or 7th day of treatment. There was also no difference in the efficacy rates between the two groups. No difference of TSS was observed between patients with RHG taking inosine pranobex and acyclovir on days 3 or 5 of the treatment, respectively. The short-term clinical recurrence rate of RHG at 3-month follow-up was much lower in the inosine pranobex group than acyclovir group. The incidence of hyperuricemia was higher in the inosine pranobex group than acyclovir group. In conclusion, inosine pranobex was as effective as acyclovir in treating RHL and RHG with significantly greater reduction of the short-term recurrence rate of herpes genitalis at 3-month follow up. Long-term recurrence rates at 6 months or longer remain to be determined. Hyperuricemia should be monitored during the treatment.

Expression of lymphatic markers in angiokeratomas.

BACKGROUND: The term angiokeratoma refers to a group of unrelated diseases with similar histopathologic features. Four clinical variants of angiokeratoma have been described. However, it is not known whether some variants of angiokeratoma are of lymphatic origin, and an immunohistochemical study of lymphatic markers has not been previously performed. METHODS: We performed an immunohistochemical study of angiokeratomas using lymphatic markers. Fifteen cases of angiokeratoma corporis diffusum, 10 cases of Fordyce angiokeratoma, 10 cases of Mibelli angiokeratoma and 10 cases of solitary angiokeratoma were examined by immunohistochemical analysis using CD31, D2-40, Prox1 and Wilms' tumor 1 (WT-1). RESULTS: The vessels of angiokeratoma corporis diffusum, Fordyce angiokeratoma and solitary angiokeratoma were usually focally positive for D2-40 and positive for Prox1, whereas the vessels of Mibelli angiokeratoma were negative for D2-40 and positive for Prox1. CONCLUSIONS: The results suggest lymphatic derivation of angiokeratoma corporis diffusum, Fordyce angiokeratoma and solitary angiokeratoma. However, the derivation of Mibelli angiokeratoma could not be determined based on the present immunohistochemical results.

CD4+FOXP3+ regulatory T cell depletion by low-dose cyclophosphamide prevents recurrence in patients with large condylomata acuminata after laser therapy.

Condylomata acuminata (CA) caused by human papillomavirus (HPV) is a common sexually transmitted disease with half a million new cases diagnosed in the United States per year and the annual increase in incidence in China. Recurrence is a major challenge for CA treatment. Recently, we demonstrated that FOXP3(+) regulatory T (Treg) cells mediate the immunosuppression in large genital warts. Here, we further report that low-dose cyclophosphamide (CY), a conventional chemotherapy drug, can effectively prevent the recurrence of large CA in clinical patients after laser therapy. Surprisingly, although 9 out of 52 patients recur six weeks after the combination treatment, the re-administration of low-dose CY alone completely eliminates most recurred lesions. We provide evidence that low-dose CY not only depletes patients' Treg cells and enhances function of HPV-specific T cells and NK cells in the periphery, but also ameliorates the immune milieu of the lesion site, leading to the elimination of remnant viruses. These findings have important clinical significance, and potentially lead to a therapeutic breakthrough for the treatment of CA.