Nobuhiro Ueno ^1 2, Yu Kobayashi ³, Aki Sakatani ², Tatsuya Dokoshi ³, Keitaro Takahashi ³, Katsuyoshi Ando ³, Shin Kashima ³, Kentaro Moriichi ³, Hiroki Tanabe ³, Yuki Kamikokura ⁴, Mishie Tanino ⁴, Mikihiro Fujiya ² 

J Clin Apher. 2025 Jun;40(3):e70030. doi: 10.1002/jca.70030.

Ulcerative colitis (UC) is a chronic inflammatory condition requiring lifelong management, with anti-tumor necrosis factor α (anti-TNF-α) agents often used for refractory cases. However, secondary loss of response (LOR) to these agents, due to anti-drug antibodies, poses a significant therapeutic challenge. This report describes a case where granulocyte and monocyte adsorptive apheresis (GMA) maintenance therapy successfully restored the efficacy of an anti-TNF-α agent in a 26-year-old male with active UC experiencing LOR to infliximab. Following GMA induction therapy and continued infliximab administration, clinical symptoms improved, fecal calprotectin levels decreased, and clinical remission was achieved. Long-term maintenance with GMA enabled sustained clinical remission, with mucosal healing observed one year post-therapy. This case suggests that GMA maintenance therapy may serve as a novel therapeutic approach for patients with active UC experiencing LOR to anti-TNF-α agents. However, further studies are warranted to elucidate the underlying mechanisms and validate its efficacy.

Yuko Higashi ^1 2, Atsuko Ibusuki ¹, Tomoko Fukushige ¹, Ryoko Sagara ¹, Risako Yonezawa ¹, Natsumi Terada ¹, Hisao Kawahira ¹, Kimiko Kazumura ³, Takuro Kanekura ¹

Ther Apher Dial. 2025 Aug;29(4):702-706. doi: 10.1111/1744-9987.70043. Epub 2025 May 25.

Introduction: Activated neutrophils play a crucial role in the development of neutrophilic dermatoses, including pustular psoriasis. Adsorptive granulocyte and monocyte apheresis (GMA) is an effective treatment for skin disorders. Although previous basic research has demonstrated neutrophil activation, no efficient method exists to assess it in clinical settings.

Methods: We measured neutrophil activity in patients with GPP who underwent GMA therapy using the FLP-H4200, a newly developed neutrophil activity evaluation system. Blood samples were collected before the first and after the fifth GMA session.

Results: In Case 1, which responded to GMA, the neutrophil activation value decreased from 118 603 to 26 234, reaching the normal range. In Case 2, the response to GMA was poor, and the neutrophil activation value decreased from 140 623 to 76 780, which remained significantly above the normal level.

Conclusion: These results suggest that the neutrophil activity evaluation system may be useful for assessing disease severity and therapeutic efficacy.

Miho Takahashi*, Hitoshi Tsuchihashi and Rei Watanabe

J. Cutan. Immunol. Allergy, 13 March 2025 Volume 8 – 2025 | https://doi.org/10.3389/jcia.2025.14441

A 41-year-old woman had been diagnosed with generalized pustular psoriasis (GPP) for 4 years. Her symptoms had been stabilized with cyclosporine (2 mg/kg/day). Despite increasing the cyclosporine dosage to 3 mg/kg/day, the skin lesions did not improve and the patient developed a fever.  A CT scan revealed a mass lesion measuring 2.5 cm × 4 cm in the right breast and axillary lymphadenopathy. Based on the CT findings, the patient was suspected of having left breast cancer. To manage GPP, granulocyte and monocyte adsorption (GMA) was initiated to minimize the possible adverse effects on the suspected cancer. During the five courses of GMA, the patient’s body temperature returned to a normal degree and the pustules and erythema gradually improved. However, the erythema on her trunk remained. GMA was selected as the initial treatment because the therapeutic strategy for the breast cancer had not yet been determined. Meanwhile, etretinate, corticosteroids, biologics, and their combination are also strong candidates for acute exacerbated GPP. Subsequently, subcutaneous brodalumab administration was introduced; brodalumab allowed the patient to concurrently undergo chemotherapy for breast cancer. The patient underwent a left breast mastectomy and was diagnosed with right breast cancer with right axillary lymph node metastasis. The patient started hormonal therapy, and tumor markers showed a decreasing trend. However, she gradually developed skin metastases, which grew despite treatment. The patient died of breast cancer 4 years after diagnosis. Brodalumab was continued for 4 years, during which no recurrence of GPP was observed.

In conclusion, due to the rarity of the disease, selecting an appropriate therapy for GPP is often challenging especially considering the management of complications. Further accumulation of the treatment experience would be desirable.

Johannes Hasskamp ¹, Christian Meinhardt ², Petrease H Patton ³, Antje Timmer ¹

Cochrane Database Syst Rev.2025 Feb 27;2(2):CD000478. doi: 10.1002/14651858.CD000478.pub5.

Background: Maintenance of remission is essential in inflammatory bowel disease (IBD) in terms of disease course and long-term prognosis. The thiopurines azathioprine and 6-mercaptopurine have longstanding merit in ulcerative colitis, but more therapeutic options have been developed. This review is an update and extension of a review last published in 2016.

Objectives: To assess the effectiveness and safety of azathioprine and 6-mercaptopurine in monotherapy or combined therapy regimens compared to placebo or active controls for the maintenance of remission in ulcerative colitis.

Search methods: We searched Cochrane Central Register of Controlled Trials (until May 2023), ClinicalTrials.gov (until May 2023), Embase (until August 2022), MEDLINE (until May 2023), and WHO ICTRP (until May 2023). We checked reference lists of the included studies and, if needed, contacted the authors to request more data or information.

Main results: We included 10 studies in the review, including 468 adult participants with ulcerative colitis. The risk of bias across these was low for most outcomes, but we considered some outcomes to have some concerns or high risk of bias due to insufficient information on concealment of allocation and outcome measurement. Based on five placebo-controlled studies, azathioprine or 6-mercaptopurine may reduce the risk of failing to maintain remission. In the thiopurine group, 45% (64/143) of participants failed to maintain remission compared to 67% (96/143) of participants receiving placebo (RR 0.66, 95% confidence interval (CI) 0.54 to 0.82; 5 studies, 286 participants; low-certainty evidence). Three studies reported withdrawals due to adverse events. Among participants on azathioprine, 4% (3/80) withdrew due to adverse events compared to 0% (0/82) of placebo participants (RD 0.04, 95% CI -0.02 to 0.09; 3 studies, 162 participants; low-certainty evidence). The evidence is of low certainty when comparing 6-mercaptopurine to 5-aminosalicylate. Based on one three-armed trial, 27% (3/11) of 6-mercaptopurine participants failed to maintain remission compared to 100% (2/2) of 5-aminosalicylate participants (RR 0.35, 95% CI 0.13 to 0.97; 1 study, 13 participants; low-certainty evidence). This trial also involved an induction phase; we only included the results for participants in remission. The single trial comparing 6-mercaptopurine to 5-aminosalicylate did not report separate data on adverse events and withdrawals due to adverse events for the subgroup with successful induction of remission, so we could not analyze these outcomes for this comparison.

Authors‘ conclusions: Low-certainty evidence suggests that azathioprine or 6-mercaptopurine therapy may be more effective than placebo for the maintenance of remission in ulcerative colitis. More research is needed to evaluate the value of therapeutic drug monitoring and the effects of various treatment modalities on long-term safety.

Namiko Abe ¹, Yuko Higashi ², Chiharu Tateishi ³, Takuro Kanekura ², Daisuke Tsuruta ³, Tomoko Kobayashi ¹, Yukari Okubo ¹

J Dermatol. 2025 Apr;52(4):642-650. doi: 10.1111/1346-8138.17667. Epub 2025 Feb 12.

Granulocyte and monocyte adsorptive apheresis (GMA) selectively removes activated granulocytes and monocytes from the peripheral blood. In 2012, GMA was approved in Japan as a treatment for generalized pustular psoriasis and localized pustular psoriasis or palmoplantar pustulosis (PPP). Limited evidence from case reports and monocentric studies suggested that GMA is an effective treatment for skin and joint symptoms of PPP with pustulotic arthro-osteitis (PAO). The present, prospective, observational study was performed at three dermatology departments in Japan to evaluate the efficacy and safety of GMA in patients with PPP with PAO. Between April 2017 and December 2020, two male and 12 female patients with PPP and PAO were enrolled. Their mean age, mean duration of skin manifestations, and mean duration of PAO symptoms was 52.8 years, 51.2 months, and 44.9 months, respectively. GMA was applied weekly over five sessions. The skin and joint symptoms were assessed at baseline, post-GMA, and at the 3-month follow-up. A total of 12 patients completed five GMA sessions, and two patients discontinued the treatment because of adverse events. Thus, 12 patients were finally assessed post-GMA, and 10 patients were assessed at the 3-month follow-up. The assessment of GMA efficacy demonstrated that the skin symptoms had remarkably improved and improved in 33.3% (4/12) and 70% (7/10) of the patients post-GMA and at the 3-month follow-up, respectively. Furthermore, the joint symptoms had remarkably improved in 66.7% (8/12) and 60% (6/10) of the patients post-GMA and at the 3-month follow-up, respectively. These results suggest that GMA is effective in treating the skin and joint symptoms of PPP with PAO.

Tomotaka Tanaka ¹, Daiki Hirano ¹, Syohei Ishimaru ¹, Keiko Arataki ¹

Cureus 2025 Jan 18;17(1):e77641. doi: 10.7759/cureus.77641. eCollection 2025 Jan.

We report the case of a 37-year-old male patient diagnosed with moderate left-sided ulcerative colitis (UC). Initial therapy with 5-aminosalicylic acid (5-ASA) was terminated within days due to exacerbation of symptoms, leading to a diagnosis of 5-ASA intolerance. Although induction of remission was achieved with prednisolone, the patient developed steroid dependency. Treatment with vedolizumab and ustekinumab subsequently failed to achieve clinical or endoscopic improvement. Intensive granulocyte and monocyte apheresis (GMA) was introduced, successfully inducing remission. However, during maintenance therapy with GMA, the patient experienced a relapse. Initiation of golimumab yielded suboptimal results, necessitating a combination therapy involving prednisolone and reintensified intensive GMA. This multimodal approach successfully achieved remission induction and maintenance. This case highlights the potential utility of intensive GMA in combination with golimumab and prednisolone for the management of refractory UC, particularly in patients with 5-ASA intolerance and failure of multiple biologic agents. A brief review of the relevant literature is included.

M Hupé , G Bouguen , A Buisson , C Landman , M Uzzan , S Nancey , C Guillaume , G Cyrielle , M Charkaoui , M Serrero , A Wampach , M Collins , R Altwegg , F Cholet , A Amiot

Journal of Crohn’s and Colitis, Volume 19, Issue Supplement_1, January 2025, Page i1338, https://doi.org/10.1093/ecco-jcc/jjae190.0858

Background: Granulocyte and monocyte adsorptive apheresis (GMA) with ADACOLUMN® (JIMRO Takasaki Japan) is an effective and safe therapeutic option for patients with mild to moderate inflammatory bowel disease (IBD) refractory to pharmacological therapy, especially ulcerative colitis (UC). The aim of this study was to report effectiveness of GMA in patients with IBD.

Methods: All consecutive active, non-operated UC patients and Crohn’s disease (CD) patients treated with GMA in 15 French tertiary-care centres from 2007 to september 2024 were assessed. Patients received 4 to 8 weekly sessions of GMA alone or in combination with previously failing advanced therapy. Patients were assessed for effectiveness at week 14 and at week 54 for those continuing GMA as maintenance therapy and at every visit for safety. Clinical remission, steroid-free clinical remission, clinical response, colectomy as well as safety were ascertained.

Results: One hundred and twenty-nine patients with IBD (75 males, median age: 40.9 IQR[29.3-58.1] years, 102 with UC, IBD duration: 7.0 [2.9-13.1] years) were included. One hundred patients (77.5%) were previously treated with immunosuppressants and 97 (72.2%) with at least one anti-TNF. In patients with UC, baseline median total Mayo score was 7 [6-12] and mean CRP level was 23.3 ± 86.0 mg/L. In patients with CD, baseline median Harvey-Bradshaw index was 9 [7.25-10.75] and mean CRP level was 21.9 ± 27.3 mg/L. In patients with UC, week 14 clinical remission, steroid-free clinical remission and response rates were 33.3%, 27.5% and 52.0%, respectively. In patients with CD, week 14 clinical remission, steroid-free clinical remission and response rates were 33.3%, 29.6% and 66.7%, respectively. At week 14, nine patients with UC and 3 patients with CD required emergent surgery. At week 14, adverse events were reported in 26 (20.2%) and were mainly related to flare of IBD in 16 (12.4%). Other adverse events which were never classified as serious included headache in 3, arthromyalgia in 3 and abdominal pain, diarrhea, grade-1 increase in liver enzymes and mild hypotension in one. At week 54, 48 patients were still treated with maintenance GMA therapy including 13 with CD and 35 with UC. At week 54, steroid-free clinical remission rates were 38.5% (5/13) in patients with CD and 60% (21/35) in patients with UC.

Conclusion: In this real world cohort of patients with refractory IBD, GMA induced steroid-free clinical remission in one third of patients with CD and UC at W14. In patients continuing GMA maintenance therapy, steroid-free clinical remission was observed in one third of patients with CD and two thirds of patients with UC. Safety profile was favourable mostly related to relapse of IBD.

Yoshifumi Hamasaki ¹, Ryo Matsuura ², Takahide Shinagawa ³, Soichiro Ishihara ³, Sozaburo Ihara ⁴, Mitsuhiro Fujishiro ⁴, Kent Doi ⁵, Masaomi Nangaku ^1 2

J Clin Med Res. 2024 Dec;16(12):625-634. doi: 10.14740/jocmr6071. Epub 2024 Dec 20.

Background: Granulocyte and monocyte adsorption apheresis (GMA) is a therapeutic option for remission induction in the active ulcerative colitis (UC) patients. Effects of high processed blood volume of GMA as remission induction therapy on the long-term prognosis of UC patients have remained unclear. For this study, we investigated the relation between re-exacerbation of UC and the processed blood volume of GMA performed as induction therapy.

Methods: Data from UC patients treated using a total of 10 GMA sessions as remission induction therapy during 2012 – 2022 were retrospectively collected and analyzed. The relation between the GMA dose, processed blood volume of GMA divided by body weight, and UC re-exacerbation requiring inpatient treatment within 1 year was evaluated.

Results: This study examined data of 72 active UC patients, with median age of 44.4 years (65% male) and median GMA dose of 34.2 mL/kg/session. Kaplan-Meier analysis showed the 1-year exacerbation-free rate was significantly higher in the higher GMA dose group than in the lower GMA dose group (P = 0.008). Cox proportional hazards regression analyses revealed a higher GMA dose as inversely associated with the re-exacerbation of UC within 1 year (hazard ratio: 0.36, 95% confidence interval: 0.17 – 0.78). Extended treatment time of GMA session beyond 60 min contributed to achieving the higher GMA dose and did not increase unexpected treatment termination because of clotting.

Conclusion: Greater processed blood volume of GMA per patient body weight may be associated with a lower 1-year exacerbation rate in UC patients.

Francisco José Fernández-Pérez ¹, Nuria Fernández-Moreno ², Estela Soria-López ², Francisco Javier Rodriguez-González ², Francisco José Fernández-Galeote ³, Ana Lifante-Oliva ⁴, Concepción Ruíz-Hernández ⁴, Elisabeth Escalante-Quijaite ⁴, Francisco Rivas-Ruiz ⁵

Gastroenterol Hepatol. 2024 Nov;47(9):502196. doi: 10.1016/j.gastrohep.2024.502196. Epub 2024 May 6. (Article in Spanish)

Introduction: Granulocyte and monocyte adsorptive apheresis (GMA) removes neutrophils and monocytes from peripheral blood, preventing their incorporation into the inflamed tissue also influencing cytokine balance. Published therapeutic efficacy in ulcerative colitis (UC) is more consistent than in Crohn’s disease (CD). We assessed clinical efficacy of GMA in UC and CD 4 weeks after last induction session, at 3 and 12 months, sustained remission and corticosteroid-free remission.

Patients and method: Retrospective observational study of UC and CD patients treated with GMA. Partial Disease Activity Index-DAIp in UC and Harvey-Bradshaw Index-HBI in CD assessed efficacy of Adacolumn® with induction and optional maintenance sessions.

Results: We treated 87 patients (CD-25, UC-62), 87.3% corticosteroid-dependent (CSD), 42.5% refractory/intolerant to immunomodulators. In UC, remission and response were 32.2% and 19.3% after induction, 35.5% and 6.5% at 12 weeks and 29% and 6.5% at 52 weeks. In CD, remission rates were 60%, 52% and 40% respectively. In corticosteroid-dependent and refractory or intolerant to INM patients (UC-41, CD-14), 68.3% of UC achieved remission or response after induction, 51.2% at 12 weeks and 46.3% at 52 weeks, and 62.3%, 64.3% and 42.9% in CD. Maintained remission was achieved by 66.6% in CD and 53.1% in UC. Up to 74.5% of patients required corticosteroids at some timepoint. Corticosteroid-free response/remission was 17.7% in UC and 24% in CD.

Conclusions: GMA is a good therapeutic tool for both in UC and CD patients. In corticosteroid-dependent and refractory or intolerant to INM patients it avoids biological therapy or surgery in up to 40% of them in one year.

Maki Setake ¹, Ryosaku Tomiyama ¹, Tomoya Kuda ², Kanetaka Maeshiro ³, Akira Hokama ⁴

Rev Esp Enferm Dig. 2024 Oct 4. doi: 10.17235/reed.2024.10795/2024. 

A 17-year-old man with ulcerative colitis (UC) presented to our hospital with neck pain and fever after vomiting. On examination, a snowflake sensation was noted in the neck. A chest radiograph showed extensive subcutaneous emphysema in the chest. CT scans showed extensive subcutaneous emphysema in the neck, shoulders and axilla, as well as pneumomediastinum and pneumothorax. A diagnosis of pneumomediastinum with exacerbation of UC was made, and he was fasted and treated with antibiotics. Intensive granulocyte and monocyte adsorption apheresis (GMA) was started for exacerbation of UC. His symptoms and the radiological findings of pneumomediastinum improved. He remained in remission on azathioprine. UC is a chronic inflammatory bowel disease (IBD) associated with extraintestinal manifestations (EIM). Very few cases have been complicated by pneumomediastinum. The increase in alveolar pressure due to vomiting and systemic inflammation-related pleural or esophageal damage may cause pneumomediastinum in this case. Prevention of progression to mediastinitis and treatment of exacerbated UC are contradictory. GMA was successful because it was not an immunosuppressive therapy. Our case highlights that rare EIM may complicate exacerbation of UC.