Yukari Okubo ¹, Ryuhei Okuyama ², Shinichi Imafuku ³, Yayoi Tada ⁴, Keiichi Yamanaka ⁵, Kazumitsu Sugiura ⁶, Yukie Yamaguchi ⁷, Masahito Yasuda ⁸, Wataru Sakamoto ⁹, Morihisa Saitoh ⁹, Akimichi Morita ¹⁰; Study Investigators

Dermatol Ther (Heidelb). . 2025 Jul;15(7):1883-1899. doi: 10.1007/s13555-025-01429-8. Epub 2025 May 19.

Introduction: Generalized pustular psoriasis (GPP) is a rare, severe, and chronic inflammatory skin disease characterized by widespread pustules that leads to unpredictable and potentially serious disease flares. Information regarding treatment status for GPP and treatment patterns for flares is important but limited as a result of the rarity of the condition. We conducted a 10-year, retrospective, longitudinal chart review of treatment patterns at GPP referral hospitals in Japan.

Methods: Eligible patients with GPP had at least 6 months of continuous observation data within 10 years after the date of protocol approval. Data were collected from patient records and annual patient reports. Patient characteristics and treatment details, including in relation to flare occurrence, were analyzed.

Results: The median age of patients (N = 205) was 53 years; 48.3% were female and most had mild or moderate GPP (66.8%). Patients commonly received nonbiologic systemic therapy (86.3%) and a similar proportion received biologics (79.5%); 95.1% received topical treatment and 22.4% received systemic adrenal corticosteroids. Use of nonbiologic systemic therapy decreased, and use of biologics increased, over the study period. During the observation period, the proportion of patients receiving biologic therapy increased after a flare (from 41.4% receiving biologics when flares occurred to 62.9% initiating a new biologic post flare).

Conclusion: In Japanese clinical practice, the evolution of treatment practices for GPP has seen an increased use of biologic therapies over time. Biologic use was common after flares; however, some flares occurred during biologic therapy, indicating a need for improved treatment options to maintain stable disease and prevent flares.

Miki Urushiyama ¹, Kunio Tarasawa ², Rintaro Moroi ¹, Hideya Iwaki ¹, Yusuke Hoshi ³, Hiroshi Nagai ¹, Yusuke Shimoyama ¹, Takeo Naito ¹, Fumihiko Kakuta ³, Hisashi Shiga ¹, Shin Hamada ¹, Yoichi Kakuta ¹, Kiyohide Fushimi ⁴, Yoshitaka Kinouchi ¹, Daiki Abukawa ³, Kenji Fujimori ², Atsushi Masamune ¹

JGH Open. . 2025 May 14;9(5):e70175. doi: 10.1002/jgh3.70175. eCollection 2025 May.

Aims: This study aimed to investigate the trends in pediatric inflammatory bowel diseases (IBD) management in Japan over the past decade.

Methods: We retrospectively analyzed data from Japan’s nationwide database from 2012 to 2022. Patients aged ≤ 15 years diagnosed with Crohn’s disease (CD) or ulcerative colitis (UC) were included. Trends in the use of biologics, capsule endoscopy, total parenteral nutrition (TPN), elemental diets, surgery, and granulocyte and monocyte apheresis (GMA) were examined using the Cochrane-Armitage and Jonckheere-Terpstra trend tests.

Results: Among the 8037 and 6153 pediatric UC and CD admissions, respectively, the use of biologics increased significantly (CD: from 46.0% to 53.6%; UC: from 15.0% to 33.0%, p < 0.0001). The use of capsule endoscopy in pediatric patients with CD increased markedly from 6.6% to 16.7% (p < 0.0001), whereas TPN use decreased from 8.4% to 3.0% (p < 0.0001). Surgery rates for patients with CD remained at approximately 5%, whereas those for patients with UC decreased (from 3.7% to 1.7%, p = 0.002). Elemental diets for pediatric patients with CD increased (from 54.4% to 66.2%, p < 0.0001). The use of GMA decreased significantly in patients with UC (from 12.1% to 2.7%, p < 0.0001).

Conclusion: The use of biologics and capsule endoscopy has increased in pediatric patients with IBD, whereas the use of more invasive treatments has decreased. These trends suggest a shift toward less invasive and more targeted therapeutic strategies in managing pediatric patients with IBD in Japan.

Sneha Annie Sebastian ¹, Oroshay Kaiwan ², Edzel L Co ³, Meghana Mehendale ⁴, Babu P Mohan

Spartan Med Res J. 2024 Sep 9;9(3):123397. doi: 10.51894/001c.123397. eCollection 2024.

Introduction: Ulcerative colitis (UC) is a chronic inflammatory bowel disorder (IBD) with periods of relapse and remission. Current advancements in clinical research have led to the development of more refined and effective medical therapy for UC.

Summary of the evidence: Traditional therapeutic agents such as 5-aminosalicylates (5-ASAs), sulfasalazine (SASP), corticosteroids, and immunomodulatory drugs have remained the gold standard for decades. However, their novel formulations and dosage regimens have changed their sequences in the medical management of UC. Several other novel drugs are in the final phases of clinical development or have recently received regulatory approval designed to target specific mechanisms involved in the inflammatory cascade for UC.

GMA has shown its efficacy in mild to moderate UC and refractory UC (steroid-dependent UC or biologic/immunologic resistant UC or lost their response to biologics) for remission induction.

Conclusions: This narrative review sought to provide a comprehensive knowledge of the potential benefits of standard and emerging therapies, including novel formulations, new chemical entities, and novel therapeutic approaches in managing UC. Keywords: Ulcerative colitis, 5- Aminosalicylic acid, sulfasalazine, corticosteroids, biologics, immunomodulators, novel formulations.

João Vilaça ¹, Orhan Yilmaz ², Tiago Torres ^1 3

Pharmaceutics. . 2024 Jul 6;16(7):908. doi: 10.3390/pharmaceutics16070908.

Generalized Pustular Psoriasis (GPP) is a rare and severe subtype of psoriasis that significantly impacts patients’ quality of life. Until recently, no specific treatment modalities were available, and treatment for GPP followed the guidelines for the treatment of plaque psoriasis, consisting of conventional treatments, such as retinoids, methotrexate, and even biologics, which although effective in some cases, may be associated with significant side effects, necessitating more effective and safe options. The pathophysiology of Generalized Pustular Psoriasis is complex and not fully understood, but there is some overlap with the pathogenesis of Plaque Psoriasis. In GPP, the innate immune system seems to play a more significant role, with the interleukin (IL)-36 pathway being fundamentally involved. Spesolimab and imsidolimab, two recently developed therapeutic agents, target the IL-36 inflammatory pathway by binding to the IL-36 receptor (IL-36R). Both biologics have already been evaluated in phase 1 and 2 clinical trials and have shown promising results in terms of safety and efficacy. IL-36 receptor inhibitors demonstrated great efficacy and good safety profile in the management of patients with GPP, demonstrating their potential to emerge as a leading treatment option. This review aims to explore and summarize the current scientific literature on the most recently developed treatments for GPP.

Dimitrii Pogorelov ¹, Anne Tschesche ¹, Galina Balakirski ¹, Silke C Hofmann ¹

Cureus. 2024 May 7;16(5):e59832. doi: 10.7759/cureus.59832. eCollection 2024 May.

Generalized pustular psoriasis of pregnancy (GPPP) is a rare dermatological condition that significantly affects maternal health and pregnancy outcomes. The treatment of this disease might be very challenging, as only a limited number of effective therapeutic options are available. If the use of systemic drugs is considered, they should ideally effectively control the systemic inflammation without harming the fetus. Here, we report the successful treatment of a severe case of GPPP in a 28-year-old woman using the tumor necrosis factor-alpha inhibitor (TNFi) certolizumab pegol. Additionally, we review the existing literature on the use of this class of drugs for treating GPPP. To date, there are only 11 reported cases of this severe skin condition treated with a TNFi. We also discuss the pathogenesis of GPPP and the rationale behind using TNFi for its treatment.

Nobuhiro Ueno Seisuke Saito Masahiro Sato Yuya Sugiyama doi: 10.21203/rs.3.rs-3037827/v1

Background: A remission induction therapy of granulocyte and monocyte adsorptive apheresis (GMA) with Adacolumn was given to patients with active Crohn’s disease (CD). However, establishing an appropriate treatment strategy for GMA in patients with active CD remains unclear. Methods: This multicenter retrospective cohort study encompassed patients with CD who underwent GMA in seven independent institutions in Japan from January 2010 to March 2023. All clinical data were obtained from medical records. This study aimed to evaluate the clinical efficacy, safety, and subsequent clinical progression after GMA in patients with CD. Result: This study enrolled 173 patients with active inflammatory bowel disease who underwent GMA with Adacolumn, and among them, 16 patients with CD with mild to moderate disease activity were analyzed. Concomitant medication, including steroids, immunomodulators, and biologics, was used in 93.7% of all cases. The overall remission and response rates were 25.0% and 68.8%, respectively. The response rate between groups concerning the frequency and total GMA sessions revealed no significant difference. Six (37.5%) patients experienced adverse events (AEs). All AEs were related to the trouble in blood access and recovered soon without any sequelae. Regarding the factors associated with response to GMA, the responder group had a significantly longer disease duration (336 vs 44 months, p = 0.036) and exhibited a relatively lower rate of intestinal strictures and a median score of a simple endoscopic score for CD (SES-CD) (9.1 vs 60 %, p = 0.063 and 10 vs 21.5, p = 0.091, respectively). Further, all patients responding to GMA received biologics that were continuously used before and after GMA. Furthermore, 36.4% of patients remained on the same biologics 52 weeks after GMA. Notably, all patients who continued the same biologics had previously experienced a loss of response to anti-tumor necrosis factor-α agent. Conclusion: Therefore, GMA may exhibit heightened effectiveness in patients with moderately active CD without severe endoscopic activity. Moreover, it represents a potential novel therapeutic option for refractory CD, particularly with insufficient response to biologics.

(PDF) The clinical efficacy and safety of granulocyte and monocyte adsorptive apheresis in patients with Crohn’s disease: A multicenter retrospective cohort study (researchgate.net)

Masi L, Ciuffini C, Petito V, Pisani LF, Lopetuso LR, Graziani C, Pugliese D, Laterza L, Puca P, Di Vincenzo F, Pizzoferrato M, Napolitano D, Turchini L, Amatucci V, Schiavoni E, Privitera G, Minordi LM, Mentella MC, Papa A, Armuzzi A, Gasbarrini A and Scaldaferri F Front. Gastroenterol. 1:1022530. doi: 10.3389/fgstr.2022.1022530

Inflammatory bowel diseases (IBD) are chronic disabling conditions with a complex and multifactorial etiology, which is still not completely understood. In the last 20 years, anti-TNF-α antagonists have revolutionized the treatment of IBD, but many patients still do not respond or experience adverse events. Therefore, new biological therapies and small molecules, targeting several different pathways of gut inflammation, have been developed of which some have already been introduced in clinical practice while many others are currently investigated. Moreover, therapeutic procedures such as leukocytapheresis, fecal microbiota transplant and stem cell transplantation are currently being investigated for treating IBD. Lastly, complementary and alternative medicine has become a field of interest for gastroenterologist to reduce symptom burden in IBD patients. In this comprehensive and updated review, a novel classification of current and developing drugs is provided.

Frontiers | Innovative, complementary and alternative therapy in inflammatory bowel diseases: A broad 2020s update (frontiersin.org)

Chiamaka L Okorie ¹, Krithika Nayudu ², Vinod E Nambudiri ^3 4

Exp Dermatol. 2024 Jan;33(1):e14934. doi: 10.1111/exd.14934. Epub 2023 Sep 19.

Deficiency of the interleukin-36 receptor antagonist (DITRA) is a rare autoinflammatory disorder caused by mutations in the IL36RN gene. This mutation leads to a lack of functional interleukin-36 receptor antagonists (IL-36Ra), which results in an overactive immune system and chronic inflammation. Despite its rarity, numerous case series and individual reports in the literature emphasize the importance of recognizing and managing DITRA. Early identification of the cutaneous signs of DITRA is crucial for accurate diagnosis and timely administration of appropriate treatment. This review article provides a comprehensive overview of the current understanding of the cutaneous, non-cutaneous and histopathological manifestations of DITRA, with a focus on reported treatments. The disease typically presents in early childhood, although the age of onset can vary. Patients with DITRA exhibit recurrent episodes of skin inflammation, often with a pustular or pustular psoriasis-like appearance. Additionally, non-cutaneous manifestations are common, with recurrent fevers and elevated acute-phase reactants being the most prevalent. The exact prevalence of DITRA is unknown. Some cases of loss-of-function mutations in the IL36RN gene, considered a hallmark for diagnosis, have been identified in patients with familial generalized pustular psoriasis (GPP). Biological therapies with inhibition of IL-12/23 and IL-17 are promising treatment options; paediatric patients with DITRA have shown complete response with mild relapses. New and emerging biologic therapeutics targeting the IL-36 pathway are also of interest in the management of this rare autoinflammatory disorder.

5.3 Granulocyte and monocyte apheresis (GMA) The use of GMA warrants further exploration.

Nobuhiro Ueno ¹, Yuya Sugiyama ¹, Yu Kobayashi ¹, Yuki Murakami ¹, Takuya Iwama ², Takahiro Sasaki ¹, Takehito Kunogi ¹, Aki Sakatani ¹, Keitaro Takahashi ¹, Kazuyuki Tanaka ³, Shinya Serikawa ⁴, Katsuyoshi Ando ¹, Shin Kashima ¹, Momotaro Muto ⁵, Yuhei Inaba ², Kentaro Moriichi ¹, Hiroki Tanabe ¹, Toshikatsu Okumura ¹, Mikihiro Fujiya

J Clin Apher.  2023 Jan 13. doi: 10.1002/jca.22040.

Background: Granulocyte and monocyte adsorptive apheresis (GMA) with Adacolumn has been used as a remission induction therapy for patients with active ulcerative colitis (UC). Herein, we investigated the influence of concomitant medications in the remission induction of GMA in patients with active UC. Methods: This multicenter retrospective cohort study included patients with UC underwent GMA in five independent institutions in Japan from January 2011 to July 2021. Factors including concomitant medications associated with clinical remission (CR) were analyzed statistically. Result: A total of 133 patients were included. Seventy-four patients achieved a CR after GMA. The multivariable analysis revealed that concomitant medication with 5-aminosalicylic acid, Mayo endoscopic subscore (MES), and concomitant medication with immunosuppressors (IMs) remained as predictors of CR after GMA. In the subgroup analysis in patients with MES of 2, concomitant medication with IMs was demonstrated as a significant negative factor of CR after GMA (P = .042, OR 0.354). Seventy-four patients who achieved CR after GMA were followed up for 52 weeks. In the multivariable analysis, the maintenance therapy with IMs was demonstrated as a significant positive factor of sustained CR up to 52 weeks (P = .038, OR 2.214). Furthermore, the rate of sustained CR in patients with biologics and IMs was significantly higher than that in patients with biologics only (P = .002). Conclusion: GMA was more effective for patients with active UC that relapsed under treatment without IMs. Furthermore, the addition of IMs should be considered in patients on maintenance therapy with biologics after GMA.

Concomitant pharmacologic medications influence the clinical outcomes of granulocyte and monocyte adsorptive apheresis in patients with ulcerative colitis: A multicenter retrospective cohort study – PubMed (nih.gov)

Iizuka M, Etou T, Sagara S.  World J Gastroenterol 2022; 28(34): 4959-4972 DOI: 10.3748/wjg.v28.i34.4959

For the optimal management of refractory ulcerative colitis (UC), secondary loss of response (LOR) and primary non-response to biologics is a critical issue. This article aimed to summarize the current literature on the use of cytapheresis (CAP) in patients with UC showing a poor response or LOR to biologics and discuss its advantages and limitations. Further, we summarized the efficacy of CAP in patients with UC showing insufficient response to thiopurines or immunomodulators (IM). Eight studies evaluated the efficacy of CAP in patients with UC with inadequate responses to thiopurines or IM. There were no significant differences in the rate of remission and steroid-free remission between patients exposed or not exposed to thiopurines or IM. Three studies evaluated the efficacy of CAP in patients with UC showing an insufficient response to biologic therapies. Mean remission rates of biologics exposed or unexposed patients were 29.4 % and 44.2%, respectively. Fourteen studies evaluated the efficacy of CAP in combination with biologics in patients with inflammatory bowel disease showing a poor response or LOR to biologics. The rates of remission/response and steroid-free remission in patients with UC ranged 32%-69% (mean: 48.0%, median: 42.9%) and 9%-75% (mean: 40.7%, median: 38%), respectively. CAP had the same effectiveness for remission induction with or without prior failure on thiopurines or IM but showed little benefit in patients with UC refractory to biologics. Although heterogeneity existed in the efficacy of the combination therapy with CAP and biologics, these combination therapies induced clinical remission/response and steroid-free remission in more than 40% of patients with UC refractory to biologics on average. Given the excellent safety profile of CAP, this combination therapy can be an alternative therapeutic strategy for UC refractory to biologics. Extensive prospective studies are needed to understand the efficacy of combination therapy with CAP and biologics.

https://pubmed.ncbi.nlm.nih.gov/36160647/

https://www.wjgnet.com/1007-9327/full/v28/i34/4959.htm