Tomotaka Tanaka

Cureus 2023 Nov 16;15(11):e48913. doi: 10.7759/cureus.48913. eCollection 2023 Nov.

The major phenotypes of inflammatory bowel disease (IBD) include ulcerative colitis (UC) and Crohn’s disease (CD), which cause debilitating symptoms, including bloody diarrhea, abdominal discomfort, and fever. Patients require life-long immunosuppressive medications, which cause adverse side effects as additional morbidity factors. However, IBD is initiated and perpetuated by inflammatory cytokines, and given that in patients with IBD myeloid lineage leukocytes are elevated with activation behavior and release inflammatory cytokines, selective depletion of elevated granulocytes and monocytes by granulomonocytapheresis is a relevant therapeutic option for IBD patients. Therefore, a column filled with specially designed beads as granulomonocytapheresis carriers for selective adsorption of myeloid lineage leukocytes (Adacolumn) has been applied to treat patients with active IBD. Patients receive up to 10 granulomonocytapheresis sessions at one or two sessions per week. During each session, the carriers adsorb up to 60% of the myeloid leukocytes from the blood that passes through the granulomonocytapheresis column. Efficacy rates in the UC setting have been as high as 85% in steroid-naïve patients, and 100% in drug-naïve, first-episode cases, but patients with a long duration of active IBD and extensive colonic lesions that have become refractory to pharmacological treatment have not responded well. However, granulomonocytapheresis has a favorable safety profile. Given that immunosuppressive medications used to treat IBD potentially may increase the risk of severe viral infection, non-drug granulomonocytapheresis should be a favorable treatment strategy. Further, by targeting granulomonocytapheresis to patients with background features and identifying a patient as a likely responder, futile use of medical resources is avoided.

Therapeutic Granulomonocytapheresis as a Non-pharmacologic Treatment Option for Inflammatory Bowel Disease: Efficacy Reports on a Wide Age Range and Disease Profile – PubMed (nih.gov)

Therapeutic Granulomonocytapheresis as a Non-pharmacologic Treatment Option for Inflammatory Bowel Disease: Efficacy Reports on a Wide Age Range and Disease Profile – PMC (nih.gov)

Muhammad Hassan Shakir 1 2, Salman A Basit 1, Syed Muhammad Hussain Zaidi 1, Sarasija Natarajan 1, Omar Z Syed 1, Mohammad Asim Amjad 1, Douglas Klamp, Cureus. 2023 Nov 6;15(11):e48399. doi: 10.7759/cureus.48399. eCollection 2023

Sweet syndrome (SS) is an acute febrile neutrophilic dermatosis. Although perceived to be rare, the disease may well have been underreported due to lack of exposure in low-volume clinical settings and due to the use of rather strict clinical criteria for diagnosis. It presents as cutaneous papules, plaques, or nodules in an asymmetric distribution that follows fever and flu-like symptoms. Data on the disease is ever-expanding. Several associations have been identified, including drugs, infections, malignancies, and autoimmune diseases. Different disease patterns and histological variants have been identified. Pathophysiology is complex and multifactorial but appears to involve mechanisms that negatively influence neutrophil apoptosis and facilitate neutrophil recruitment. The existing diagnostic criteria exclude cases with vasculitis; over time, cases of neutrophilic dermatoses with vasculitis have been reported as SS as long as other criteria were met. Newer diagnostic models have been proposed, some arguing against the exclusion of vasculitis. Steroids continue to be the mainstay of treatment, and steroid responsiveness continues to be a part of the diagnostic criteria, although newer treatment modalities have been used and have shown promise. No established guidelines exist for management. We present a case of Idiopathic SS with vasculitis along with a brief review of the existing literature. We agree to the inclusion of vasculitis as proposed by the newer diagnostic criteria.

Mauro Mastronardi, Elisabetta Cavalcanti, Nunzia Labarile, Raffaele Armentano, Francesco Gabriele, Margherita Curlo, Therapeutic Advances in Chronic Disease. 2023;14. doi:10.1177/20406223231194190

Extraintestinal manifestations occur rather frequently in ulcerative colitis (UC) and Crohn’s disease patients and are usually related to an exacerbation of the underlying intestinal bowel disease but sometimes may run a course independent of the inflammatory bowel diseases (IBD). About one-third of patients with IBD develop extraintestinal manifestations, such as pyoderma gangrenosum (PG). PG is an uncommon inflammatory skin disorder of unknown pathogenesis. There are no specific serological or histological markers, and diagnosis is predominantly clinical. Topical and systemic therapies are both vital aspects of treatment and immune modulators have been used with increasing success in recent years, although immunosuppressive drugs raise some concerns due to an increased risk of serious and opportunistic infections and cancer, particularly in elderly and comorbid patients, underlining the unmet need for safer alternative therapies. Thus, in this case report, we highlighted an adsorptive granulocyte/monocyte apheresis (GMA) as a new therapeutic possibility in IBD patients with extraintestinal manifestations. We report a case of a 60-year woman with a history of UC with a Mayo grade 3 score which was associated with a PG. Given that the patients maintained clinical remission with vedolizumab, we preferred not to perform a combined treatment with other antitumor necrosis factor-alpha or ciclosporin, thus avoiding an increased risk of serious infections in the patient. Therefore, we performed the extracorporeal leukocyte apheresis. The patient progressed favorably, with progressive improvement of skin and bowel disease. Therefore, adsorptive GMA has a very favorable safety profile and has been confirmed in numerous studies. In this study, we underlined that an intensive regimen of GMA paves the way to an ideal option for patients with severe and refractory PG complicated with UC.

Mauro Mastronardi 1, Elisabetta Cavalcanti 2, Nunzia Labarile 1, Raffaele Armentano 3, Francesco Gabriele 4, Margherita Curlo 1 Ther Adv Chronic Dis. 2023 Nov 3:14:20406223231194190. doi: 10.1177/20406223231194190.

Extraintestinal manifestations occur rather frequently in ulcerative colitis (UC) and Crohn’s disease patients and are usually related to an exacerbation of the underlying intestinal bowel disease but sometimes may run a course independent of the inflammatory bowel diseases (IBD). About one-third of patients with IBD develop extraintestinal manifestations, such as pyoderma gangrenosum (PG). PG is an uncommon inflammatory skin disorder of unknown pathogenesis. There are no specific serological or histological markers, and diagnosis is predominantly clinical. Topical and systemic therapies are both vital aspects of treatment and immune modulators have been used with increasing success in recent years, although immunosuppressive drugs raise some concerns due to an increased risk of serious and opportunistic infections and cancer, particularly in elderly and comorbid patients, underlining the unmet need for safer alternative therapies. Thus, in this case report, we highlighted an adsorptive granulocyte/monocyte apheresis (GMA) as a new therapeutic possibility in IBD patients with extraintestinal manifestations. We report a case of a 60-year woman with a history of UC with a Mayo grade 3 score which was associated with a PG. Given that the patients maintained clinical remission with vedolizumab, we preferred not to perform a combined treatment with other antitumor necrosis factor-alpha or ciclosporin, thus avoiding an increased risk of serious infections in the patient. Therefore, we performed the extracorporeal leukocyte apheresis. The patient progressed favorably, with progressive improvement of skin and bowel disease. Therefore, adsorptive GMA has a very favorable safety profile and has been confirmed in numerous studies. In this study, we underlined that an intensive regimen of GMA paves the way to an ideal option for patients with severe and refractory PG complicated with UC.

N.D. Salazar Parada1, M. Algara San Nicolas1,A. Suárez-Saro Fernández1, A. Masedo1, C. Yela San Bernardino1,C. Begoña1, P. Martínez Montiel1, I. Fernández Vázquez1

UEG journal 2023 SUPPLEMENT ABSTRACT UEG Week 2023 Poster Presentations 15 October 2023 page 1047

Introduction: Despite the importance of granulocytoapheresis (GCA) in the treatment of inflammatory bowel disease (IBD), its effectiveness in steroid-dependent and steroid-refractory IBD has not been widely evaluated, the approaches are heterogeneous and data on efficacy and safety remain limited in our population.
Aims & Methods: This study aims to assess the effectiveness of GCA for induction of remission and maintenance in patients with steroid-dependent and steroid-refractory IBD in the real-world practice.
Retrospective cohort of patients with steroid-dependent and steroid-refractory colonic IBD, in which GCA was used as induction of remission and maintenance treatment between January-2015 to January-2023. We
analyze demographics, disease characteristics, prior exposure including biologic agents. The success of GCA was defined on a decrease of at least 3 points in the True-love score for Ulcerative Colitis (UC) and a decrease of
at least 100 points in the CDAI for Crohn Disease (CD). To analyze predictive factors of treatment success we performed a univariate and multivariable analysis.
Results: 49 patients were included. 5 cycles of apheresis were performed in the first 3 weeks as induction and at least 10 cycles of apheresis as maintenance in the next 6 months.

75 % (37 / 49) had UC, 86.4 % (32 / 37) were steroid-refractory while 13.6 % (5 / 37) steroid-dependent, 54 % (20 / 37) male; median age 60 ± 10.5 years with a mean of 10.5 years from diagnosis. 67.7 % (25 / 37) had received at least 1 biological treatment in the past, 43.5 % (17 / 39) ≥ 2 biological. After induction, 75 % (28 / 37) responded to treatment, 62 % (23 / 37) continued with maintenance therapy of which 67 % (15 / 23) responding. Mean PCR and calprotectin were 3,16 mg / dl and 2038 mg / dl before treatment, 1.45mg / dl and 1025 mg / dl after induction, 1.15 mg / dl and 900 mg / dl after maintenance, respectively.

25 % (12 / 49) had CD, 50 % (6/12) male; median age 62 ± 9.8 years, 75% (9 / 12) steroid-refractory and 25 % (3 / 12) steroid-dependent, with a mean of 9 years from diagnosis, 67.7 % had received at least one biological
treatment in the past. After induction, 58 % (7 / 12) responded, 80 % (10 /12) continued with maintenance with 50 % (5 / 10) responding. Mean CRP and calprotectin were 3.16 mg / dl and 3645 mg / dl before treatment, 1.7
mg / dl and 2473 mg / dl after induction, 1.14 mg / dl and 623 mg / dl after maintenance.
Factors such as smoking, extent of disease, longer disease course and lack of response to previous treatments, were not significantly related to response in either induction or maintenance.
No patient had major adverse events recorded.
Conclusion: GCA appears to be safe and effective for inducing and maintaining clinical remission in patients with IBD, especially in patients with UC. No significant differences were found in disease extension, duration or
lack of response to previous treatments.

Makoto Naganuma ¹, Taku Kobayashi ², Reiko Kunisaki ³, Katsuyoshi Matsuoka ⁴, Shojiro Yamamoto ⁵, Ami Kawamoto ⁶, Daisuke Saito ⁷, Kosaku Nanki ⁸, Kazuyuki Narimatsu ⁹, Hisashi Shiga ¹⁰, Motohiro Esaki ¹¹, Shinichiro Yoshioka ¹², Shingo Kato ¹³, Masayuki Saruta ¹⁴, Shinji Tanaka ¹⁵, Eriko Yasutomi ¹⁶, Kaoru Yokoyama ¹⁷, Kei Moriya ¹⁸, Yoshikazu Tsuzuki ¹⁹, Makoto Ooi ²⁰, Mikihiro Fujiya ²¹, Atsushi Nakazawa ²², Takayuki Abe ²³, Tadakazu Hisamatsu ⁶; Japanese UC Study Group J Gastroenterol. 2023 Dec;58(12):1198-1210. doi: 10.1007/s00535-023-02048-w. 

Background: This multicenter observational cohort study aimed to evaluate the utilization and short-term efficacy of advanced therapy (AT) in hospitalized patients with acute severe ulcerative colitis (ASUC).

Methods: In total, 221 patients with ASUC were enrolled between August 2020 and July 2021. The primary endpoint was clinical remission (CR, defined as a patient-reported outcome score < 2 with no blood in the stool) rate on Day 7 and 14 in hospitalized patients who received corticosteroids (CS) and AT.

Results: Among patients with ASUC, 120 and 101 patients received CS or any AT as first-line treatment, respectively. The CR rates on Day 7 and 14 were 22.5% and 35.0%, respectively, in hospitalized patients who received CS as first-line treatment. Most patients who used ATs had CS-dependent or frequent recurrences. Eight different ATs (apheresis, tacrolimus, infliximab, golimumab, tofacitinib, vedolizumab, ustekinumab, and cyclosporine) were used as first-line treatment in patients with ASUC, and the CR rates on Day 7 and 14 were 16.8% and 29.7%, respectively. Twenty-five patients received the second ATs after hospitalizations, and the CR rates on Day 7 and 14 were 0% and 12%, respectively. The CR rates on Day 14 were significantly higher in patients who changed to AT than in those whose dose of CS increased (34.0% vs 10.7%, p = 0.020) among patients who had already used CS before hospitalization.

Conclusion: Most first-use ATs were effective for patients with ASUC, while second-use ATs might have had limited benefits in inducing CR. These findings may contribute to considerations for the management of hospitalized patients.

Real-world efficacy and safety of advanced therapies in hospitalized patients with ulcerative colitis – PubMed (nih.gov)

Real-world efficacy and safety of advanced therapies in hospitalized patients with ulcerative colitis | Journal of Gastroenterology (springer.com)

Filippo Vernia ¹, Angelo Viscido ¹, Giovanni Latella ¹J Clin Apher. 2023 Dec;38(6):746-754

Adsorptive cytapheresis proves effective in a proportion of patients affected by ulcerative colitis. Relatively high cost and the need for apheresis facilities, prevented the widespread use of this therapeutic approach. More so following the introduction of anti-TNFα biosimilars which proved both effective and inexpensive. Anti-TNFα agents, however, are burdened by high rate of primary and secondary non-response and prompt switching to new, high-cost biologics, and small molecules. The present review analyzes advantages and disadvantages of adsorptive cytapheresis in the present clinical scenario and suggests its repositioning in the therapeutic workup of selected subgroups of ulcerative colitis patients. The extremely favorable safety profile makes adsorptive cytapheresis a viable therapeutic option in elderly and high-risk UC patients, as well as potential second-line treatment in corticosteroid-dependent patients and poor responders to first-line biologics.

Adsorptive cytapheresis in ulcerative colitis: A non-pharmacological therapeutic approach revisited – PubMed (nih.gov)

Adsorptive cytapheresis in ulcerative colitis: A non‐pharmacological therapeutic approach revisited – Vernia – 2023 – Journal of Clinical Apheresis – Wiley Online Library

Yue Feng, Weihua Feng, Mei Xu, Chaoping Wu, Huanhuan Yang, Yu Wang, Huatian Gan, Rev Esp Enferm Dig 2023. doi:
10.17235/reed.2023.9808/2023.

Background: the association between sarcopenia and treatment outcomes in inflammatory bowel disease (IBD) is currently a subject of controversy.
Methods: a systematic search was performed of PubMed, Embase, Web of Science, and the Cochrane Library for studies published until April 2023. The quality assessment of each included study was performed using the Newcastle-Ottawa
Scale.
Results: seventeen studies were included with 2,895 IBD patients. Sarcopenia exhibited an increased risk of treatment failure (OR = 2.00, 95 % CI: 1.43-2.79) and notably increased the need for surgery (OR = 1.54, 95 % CI: 1.06-2.23) as opposed to a pharmacologic treatment plan change (OR = 1.19, 95 % CI: 0.71-2.01) among IBD patients. However, no significant association was found between sarcopenia and treatment failure in corticosteroid (OR = 1.21, 95 % CI: 0.55-2.64) or biologic agent (OR = 1.65, 95 % CI: 0.93-2.92) cohorts. Sarcopenia was also linked to elevated treatment failure risks in patients with Crohn’s disease (OR = 1.82, 95 % CI:1.15-2.90) and those diagnosed with ulcerative colitis (OR = 2.55, 95 % CI: 1.05-6.21), spanning both Asian (OR = 1.88, 95 % CI: 1.29-2.74) and non-Asian regions (OR = 2.17, 95 % CI: 1.48-3.18).
Conclusions: sarcopenia was considered as a novel marker for use in clinical practice to predict treatment failure, specifically, the need for surgery in IBD patients. This distinct cohort necessitates clinical attention and tailored care strategies.

Yoshikazu Tsuzuki, Rie Shiomi, Hisashi Matsumoto, Kazuya Miyaguchi, Takeru Kusano, Hideki Ohgo, Hidetomo Nakamoto, Hiroyuki Imaeda J. Clin. Biochem. Nutr. 2023, 72 (1): 68-73.

Several new treatments for ulcerative colitis have been developed recently. The depletion of leukocytes by granulocyte and monocyte adsorption apheresis (GMA) was developed and adapted for patients with ulcerative colitis with rare adverse events. We investigated whether treatment with GMA and prednisolone (GMA + PSL) is more effective than PSL alone for patients with moderate to severe ulcerative colitis. Forty-seven patients with moderate to severe ulcerative colitis were retrospectively analyzed. Among the 47 patients, 27 received PSL, while 20 received GMA + PSL. The clinical activity of ulcerative colitis was evaluated using the Lichtiger clinical activity index (CAI) and serum levels of C-reactive protein. Mayo endoscopic score (MES) was used to examine endoscopic activity. The clinical remission rate was significantly higher in the GMA + PSL group than in the PSL group (65% vs 29.6%, p = 0.0206). The mucosal healing rate was also significantly higher in the GMA + PSL group than in the PSL group (60% vs 26%, p = 0.0343). The combination of GMA and steroids may be more effective than steroids alone for inducing clinical remission and mucosal healing in patients with moderate to severe ulcerative colitis.

JCM | Free Full-Text | An Update on Current Pharmacotherapeutic Options for the Treatment of Ulcerative Colitis (mdpi.com)

ja (jst.go.jp)

Laura Gnesotto ¹, Guido Mioso ¹, Mauro Alaibac ¹

Exp Ther Med 2022 Jun 24;24(2):536. doi: 10.3892/etm.2022.11463. eCollection 2022 Aug. DOI: 10.3892/etm.2022.11463

Adsorptive granulocyte and monocyte apheresis (GMA) is an extracorporeal treatment that selectively removes activated myeloid lineage leukocytes from peripheral blood. This technique consists of a column with cellulose acetate beads as absorptive leukocytapheresis carriers, and was initially used to treat ulcerative colitis. A literature search was conducted to extract recently published studies about the clinical efficacy of GMA in patients with different skin disorders, reporting information on demographics, clinical symptoms, treatment and clinical course. Dermatological diseases, in which GMA has been performed, include generalized pustular psoriasis, pyoderma gangrenosum, palmoplantar pustular psoriasis, Behcet’s disease, Sweet’s syndrome, adult-onset Still’s disease, impetigo herpetiformis, reactive arthritis, acne and hidradenitis suppurativa syndrome, cutaneous allergic vasculitis and systemic lupus erythematosus. In most patients, GMA was started after the failure of conventional therapeutic options and it was helpful in the majority of cases. Based on the information summarized, GMA could be considered a valid non-pharmacological treatment option for patients with several dermatological conditions, which are difficult to treat with other pharmacological preparations.

 PASH syndrome; cutaneous allergic vasculitis; granulocyte and monocyte apheresis; neutrophilic dermatoses; reactive arthritis; systemic lupus erythematosus.

https://pubmed.ncbi.nlm.nih.gov/35837066/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257973/