The effect of early radiofrequency turbinate reduction, intranasal steroid, and antihistamine H-1 on persistent allergic rhinitis: a randomized clinical trial

Article

Author: Harahap, Alida ; Dharma, Rahayuningsih ; Rengganis, Iris ; Wardhani, Retno S ; Irawati, Nina ; Lisnawati, Lisnawati ; Bashiruddin, Jenny

OBJECTIVE:

We aimed to evaluate the effect of radiofrequency turbinate reduction as an initial treatment on clinical improvement, inflammatory mediators, and remodeling process.

METHODS:

Between July 2018-February 2020, 32 patients with moderate-severe persistent AR were randomly divided into 2 groups. Intervention group received radiofrequency turbinate reduction followed by intranasal steroid and Antihistamine H-1 (AH-1), control group received intranasal steroid and AH-1. Both groups were evaluated for clinical improvement (using visual analogue scale based on total nasal symptoms score, peak nasal inspiratory flow, and turbinate size using imageJ) after 4 and 8 weeks of treatment. Inflammatory mediators (ELISA from nasal secretions was performed to measure ECP, IL-5, and HSP-70) and remodeling markers (nasal biopsy followed by immunohistochemistry examination was performed to evaluate MMP-9, TIMP-1, and PAI-1) were evaluated in week 4.

RESULTS:

Three patients dropped out of the study, resulting in 16 patients in intervention group and 13 patients in control group. At week 4, clinical response improved significantly in the intervention group compared to control group (Chi-Square test, p < 0.05). Compared to control, intervention group experienced a reduction of IL-5 and no significant change in ECP level (Mann Whitney test, p > 0.05). Reduction in the ratio of MMP-9/TIMP-1 were significantly higher in intervention group (unpaired t-test, p < 0,05). Meanwhile, increase in HSP-70 in the intervention group was slightly lower than in control group, but the difference with control group was not significant (Mann Whitney test, p > 0.05).

CONCLUSION:

Early radiofrequency turbinate reduction followed by pharmacotherapy given to persistent moderate-severe AR patients give more improvement only in early clinical symptoms and reduce MMP-9/TIMP-1 ratio, thus it might be suggested as one of the adjuvant therapies for the management of moderate-severe persistent AR. However, further investigation with a larger sample size and longer follow-up period is needed.

LEVEL OF EVIDENCE:

1B.

01 Oct 2020·The journal of allergy and clinical immunology. In practiceQ1 · MEDICINE

Symptomatic Dermographism: A Systematic Review of Treatment Options

Q1 · MEDICINE

Review

Author: Ungprasert, Patompong ; Jantanapornchai, Nuttagarn ; Kiratiwongwan, Rungsima ; Rujitharanawong, Chuda ; Hawro, Tomasz ; Chularojanamontri, Leena ; Tuchinda, Papapit ; Maurer, Marcus ; Kulthanan, Kanokvalai

BACKGROUND:

Symptomatic dermographism (SD), the most common form of chronic inducible urticaria, presents with transient wheals accompanied by itching in response to scratching. Little is known about available treatment options and their efficacy in SD.

OBJECTIVE:

To systematically review the efficacy of treatment options for patients with SD.

METHODS:

Using predefined search terms, we searched for relevant literature published until September 2019. The systematic review process was consistent with Preferred Reporting Items for Systematic Reviews and Meta-Analysis recommendations.

RESULTS:

The 23 studies identified included 15 randomized controlled trials; 22 and 17 assessed treatment responses in patients with SD by provocation/threshold testing and patient/physician clinical assessment, respectively. Thirteen different treatments were investigated in a total of 430 adult patients. The most frequently studied therapy, first-generation H₁-antihistamines, showed variable efficacy and significant side effects. In contrast, second-generation H₁-antihistamines (2^ndAH₁), in all studies, were effective and well tolerated. Monotherapy with an H₂-antihistamine (AH₂) was not effective, whereas adding an AH₂ increased the efficacy of treatment with an H₁-antihistamine (AH₁). SD improved with omalizumab. All other treatments were only investigated in small, unrepeated, and/or uncontrolled studies. There are no studies on updosing of 2^ndAH₁.

CONCLUSIONS:

The available SD studies are heterogeneous, mostly monocentric, old, small, and unrepeated, pointing to a high need for more and better studies. We suggest that 2^ndAH₁ should be the first-line treatment. In uncontrolled cases, the combination of AH₁ and AH₂ may be tried. Even though there is no evidence of its efficacy over standard dosage, updosing of 2^ndAH₁ may be considered based on the extrapolation of evidence from chronic spontaneous urticaria; omalizumab should be added in recalcitrant patients.

03 Oct 2019·OncoimmunologyQ2 · MEDICINE

Intratumorally delivered formulation, INT230-6, containing potent anticancer agents induces protective T cell immunity and memory

Q2 · MEDICINE

ArticleOA

Author: Bender, Lewis H. ; Jones, Jennifer C. ; Tiwary, Shweta ; Pasquet, Lise ; Xia, Zheng ; Bloom, Anja C. ; Berzofsky, Jay A. ; Terabe, Masaki ; Morales-Kastresana, Aizea ; Walters, Ian ; Clark, Katharine ; Jiang, Tianbo

The benefits of anti-cancer agents extend beyond direct tumor killing. One aspect of cell death is the potential to release antigens that initiate adaptive immune responses. Here, a diffusion enhanced formulation, INT230-6, containing potent anti-cancer cytotoxic agents, was administered intratumorally into large (approx. 300mm³) subcutaneous murine Colon26 tumors. Treatment resulted in regression from baseline in 100% of the tumors and complete response in up to 90%. CD8⁺ or CD8⁺/CD4⁺ T cell double-depletion at treatment onset prevented complete responses, indicating a critical role of T cells in promoting complete tumor regression. Mice with complete response were protected from subcutaneous and intravenous re-challenge of Colon26 cells in a CD4⁺/CD8⁺ dependent manner. Thus, immunological T cell memory was induced by INT230-6. Colon26 tumors express the endogenous retroviral protein gp70 containing the CD8⁺ T-cell AH-1 epitope. AH-1-specific CD8⁺ T cells were detected in peripheral blood of tumor-bearing mice and their frequency increased 14 days after treatment onset. AH-1-specific CD8⁺ T cells were also significantly enriched in tumors of untreated mice. These cells had an activated phenotype and highly expressed Programmed cell-death protein-1 (PD-1) but did not lead to tumor regression. CD8⁺ T cell tumor infiltrate also increased 11 days after treatment. INT230-6 synergized with checkpoint blockade, inducing a complete remission of the primary tumors and shrinking of untreated contralateral tumors, which demonstrates not only a local but also systemic immunological effect of the combined therapy. Similar T-cell dependent inhibition of tumor growth was also found in an orthotopic 4T1 breast cancer model.

News (Medical) associated with AH-001

15 May 2023

·www.prnewswire.com

AnHorn Medicines Presents Research of Novel Protein Degrader for Topical Use at ISID Meeting 2023

Preclinical data highlights AH-001 as potentially compelling targeted dermatology treatment options TAIPEI, May 15, 2023 /PRNewswire/ -- AnHorn Medicines, a private biotechnology company focused on developing precision medicines for degrading disease-causing proteins, presented its potential first-in-class protein degrader program, AH-001, at the First International Societies for Investigative Dermatology Meeting (ISID 2023) in Tokyo. AnHorn Medicines presented on May 12nd at the First International Societies for Investigative Dermatology Meeting (ISID 2023) as an oral presentation at 3:30 p.m. - 6:00 p.m. JST (UTC+9) (Presentation #1116) during the Concurrent Mini-Symposium 10-Pharmacology and Drug Development. The full abstract for the presentation is available here. AH-001 is a promising small molecule protein degrader program that effectively reverses dihydrotestosterone (DHT)-induced hair loss in preclinical studies. The local topical treatment of AH-001 stimulates hair follicle regrowth and reduces the risk of potential adverse effects by avoiding systematic exposure, resulting in a better safety profile. AnHorn Medicines believes that AH-001 has significant potential as a new treatment for androgenetic alopecia (AGA). AnHorn Medicines plans to advance the AH-001 program and complete US and Taiwan IND filing as part of its milestones following the recently closed Series A financing. Taiwania Capital led the Series A financing, with participation from TaiAn Technologies, Industrial Technology Investment Corporation, Hong Tai Electric Industrial, Black Marble Capital Management, Mega Venture Capital, Sunplus Technology, and NCTU Angel Club. The funding enables AnHorn Medicines to accelerate pipeline growth, advance drug candidate development, and enhance its platform capabilities to design bi-functional degraders and molecular glues that target known drivers of cancers and other diseases unaddressed by conventional methods. About AH-001 AH-001 is a topical administered protein degrader that efficiently degrades endogenous androgen receptor protein by recruiting E3 ubiquitin ligase. Preclinical data demonstrates that AH-001 has significant efficacy in reversing hair loss induced by dihydrotestosterone (DHT) with the topical administration, avoiding systematic exposure and reducing potential adverse effects to achieve a better safety profile. AH-001 shows great potential for the treatment of androgenetic alopecia (AGA). About AnHorn Medicines AnHorn Medicines is a biotechnology company developing a next-generation protein degradation platform that targets cellular disease-causing proteins. The company's proprietary drug discovery platform provides a unique approach to rationally design bi-functional degrader and molecular glue to have differentiated drug profiles. AnHorn Medicines was founded in 2020, headquarters in Taipei, Taiwan. The founder, Dr. Chu-Chiang Lin, has over 20 years solid experience in drug discovery and development. The drug discovery team consists of personnel in medicinal chemistry, structural biology, machine learning-based chemistry, and pharmacology. For more information, please visit and follow us on Linkedin. SOURCE AnHorn Medicines

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Indication	Highest Phase	Country/Location	Organization	Date
Androgenetic Alopecia	Preclinical	TW	AnHorn Medicines Co., Ltd.Startup	-

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