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Granulocyte and monocyte/macrophage apheresis for the treatment of immune-mediated inflammatory arthropathies: case reports

Carro Martínez AV, Montolio Chiva L, Robustillo Villarino M. Drugs Context. 2021;10:2021-8-5.

Drug therapy of immune-mediated inflammatory arthropathies is not always satisfactory, and there is a risk of adverse events. Granulocyte and monocyte/macrophage apheresis (GMA) is a non-pharmacological therapeutic option that is beneficial and very well tolerated. GMA involves passing blood through a column with cellulose acetate beads to remove increased and activated myeloid lineage cells and improve the cytokine profile. The technique reduces pain and inflammation. We present four clinical reports that illustrate the clinical uses of GMA with the medical device Adacolumn® in patients with different backgrounds and immune-mediated inflammatory arthritis. The results were positive, and no adverse events were reported..

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Granulocyte and Monocyte Adsorptive Apheresis for Ulcerative Colitis in a Patient with Low Bone Mineral Density Due to Fanconi-Bickel Syndrome

In conclusion, our experience with the current case suggests that GMA may be useful as remission induction therapy for patients with underlying disorders who have a low
BMD and who cannot be treated with steroids. We recommend further investigations be conducted to establish a detailed consensus concerning the appropriate timing and patient selection for GMA therapy

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Leukocytapheresis for rheumatoid arthritis cases that are super-resistant to any class of biological drugs and tofacitinib

Shunsuke Mori Transfusion and Apheresis Science Volume 59, Issue 6, December 2020, 102920 doi: 10.1016/j.transci.2020.102920

Many biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) are currently available as treatment options for rheumatoid arthritis (RA), but a subset of RA patients shows inadequate responses to any of these DMARDs. This phenomenon, which we call super-resistance, is becoming a serious concern. In this study, I present two cases of super-resistant RA in which patients failed to respond to treatment with bDMARDs of any class as well as to tsDMARD therapy with tofacitinib. In these cases, leukocytapheresis (LCAP), a treatment that removes overabundant leukocytes from the body, rapidly induced low disease activity and made patients subsequently responsive to previously ineffective DMARDs. My experience with the present cases suggests that LCAP is worth considering as an alternative therapeutic option for the management of RA patients with super-resistance to DMARD therapies.

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Leukocytapheresis Therapy for Rheumatoid Arthritis: Results Compared with Control Trial

Jia HuangQian WangYongjing ChengYingjuan ChenMing GaoFeng YangBingyao MuRongwei ZhouCibo Huang,

Altern Ther Health Med. 2020 Jul;26(4):36-42.

Context: Rheumatoid arthritis (RA) is a chronic multisystem autoimmune disease, mainly characterized by synovitis and with symmetrical joint involvement. LCAP therapy for RA patients has been shown to be safe and efficacious in some developed countries for over a decade.

Objective: The study intended to evaluate the efficacy and safety of leukocytopheresis (LCAP) for treatment of rheumatoid arthritis (RA) and to study the influence of treatment on the levels of various serum cytokines. Design: The study was a nonblinded, nonrandomized, controlled trial. Setting: The study took place in the Department of Rheumatology and Immunology at Beijing Hospital at the National Center of Gerontology in Beijing, China. Participants: Participants were 51 patients with RA at the hospital with a 28-joint disease activity score (DAS28) exceeding the 3.20 needed to fulfill the classification criteria of the American College of Rheumatology (ACR). Intervention: Participants were divided into 2 groups. One group (intervention group) received LCAP therapy (n = 20), while the control group (n = 31) received disease-modifying antirheumatic drugs (DMARDs). Patients receiving the LCAP therapy were treated using a Cellsorba column every 5 days for a total of 5 treatments. Outcome measures: Clinical assessment of participants’ symptoms included: (1) a tender-joint count, (2) a swollen-joint count, (3) erythrocyte sedimentation rates (ESR), (4) C-reactive protein levels (CRP), (5) a visual analog scale (VAS) for pain, (6) the DAS28 C-reactive protein (DAS28-CRP) scores, and the Health Assessment Questionnaire Disability Index (HAQ-DI). The study also evaluated participants’ scores for the American College of Rheumatology (ACR) Core Data Set. Serum collected before and after therapy from both groups was analyzed for the levels of bradykinin, serotonin, heat shock protein 70, human CXC-chemokine ligand 16 (CXCL16), prostaglandin E2, and macrophage inflammation protein 1α. Results: At week 4 for participants receiving the LCAP therapy, ACR20, ACR50, and ACR70 were observed in 55%, 30%, and 20% of patients, respectively, compared to 19.4%, 3.2%, and 0% for patients in the control group (P < .05). Also, at week 24 of LCAP therapy, ACR20, ACR50, and ACR70 were observed in 70%, 50%, and 30% of patients, respectively, which was significantly higher than the 25.8%, 12.9%, and 3.2% of patients in the control group (P < .05). The serum levels of CXCL16 and serotonin were significantly reduced in the LCAP group compared with control group. Conclusions: This study indicated that LCAP therapy can significantly decrease RA disease activity and is a safe and effective alternative therapy. LCAP therapy significantly reduced serum CXCL16 and serotonin levels, offering a putative mechanism by which it improves the articular symptoms of RA.

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Granulocyte and monocyte adsorption apheresis as an effective treatment for Reiter disease

J L Cabriada 1E DomènechN IbargoyenV HernándezJ ClofentD GinardI Gutiérrez-IbarluzeaJ Hinojosa, J clin. Exp.dermatology 2012 (37),3, 241-244

Reiter disease (RD) is characterized by a triad of sterile arthritis, urethritis and conjunctivitis. The conditions occur concomitantly or sequentially, and are associated with mucocutaneous features such as circinate balanitis and stomatitis. Arthritis usually occurs in attacks followed by recovery, but it sometimes progresses to permanent damage of the affected joints. Because the symptoms of this disorder are attributable to activated neutrophils, we assessed the efficacy of granulocyte and monocyte adsorption apheresis (GCAP) in a 73-year-old man with RD who had skin rashes on his penis, scrotum and right hand, with severe arthralgia. The patient’s skin rash and joint pain responded dramatically to five sessions of GCAP delivered at intervals of 5 days. We present a detailed description of the patient and discuss the mechanisms of GCAP, and suggest that GCAP may be useful for treating RD.

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Partial remission of refractory RA after Adacolumn cytapheresis: a case report

L Bazzichi 1T GiulianoA RossiA MazzoniT GrazziniF De FeoC GiacomelliF ScatenaS Bombardieri, Rheumatol Int. 2008 Jan;28(3):295-7.

We report on a female case of rheumatoid arthritis (RA) with hepatitis C virus comorbidity. The patient was treated once weekly over ten consecutive weeks with Adacolumn device. Clinical assessment and HCV-RNA concentration were monitored at weeks-1, 4, 9, 14 and during follow-up over 6 months. At the end of the treatment: the number of tender and swollen joints, patient’s global assessment of disease activity (VAS), physician’s VAS, C-reactive protein (CRP) decreased, respectively; ACR response was >20. This improvement was maintained for over 2 months. At week 38, the patient was re-treated achieving again an ACR response >20.

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Treatment of inflammatory immunologic disease: Leukocytapheresis for inflammatory immunologic disease (tentative)

Mamoru Watanabe 1Daisuke KubotaMasakazu NagahoriTakanori Kanai , Intern Med
. 2007;46(16):1305-6.

Opinion about effectiviness, safety , number of treated patientes and potential indications of LCAP and GMA.

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Pilot clinical study of Adacolumn cytapheresis in patients with systemic lupus erythematosus

Helmut Soerensen 1Jana-Maria Schneidewind-MuellerDoris LangeNobuhito KashiwagiMarita FranzTakashi YokoyamaWolfgang Ramlow, Rheumatol Int. 2006 Mar;26(5):409-15.

The aim of this study is to investigate the clinical effects of cytapheresis using the Adacolumn system (selective removal of circulating monocytes and granulocytes by means of an extracorporeal type column) in patients with active systemic lupus erythematosus (SLE). An open uncontrolled multicenter pilot study was conducted in 18 SLE patients who were showing a SLEDAI score of 8 or more under conventional medication. Patients with lupus nephritis (>class 1, WHO classification) were excluded. Extracorporeal cytapheresis with the Adacolumn system was administered once a week for five consecutive weeks. The efficacy of the treatment was evaluated using the SLEDAI for 10 weeks after the first cytapheresis session. The median SLEDAI decreased from 16 at baseline to six at week 11 (10 weeks after the first apheresis) (p<0.001). Significant improvements in musculoskeletal and dermal systems were observed. Arthritis and alopecia were present in 14 and nine patients at baseline and this number decreased to five and one patients, respectively by week 11. Three mild and one moderate adverse events out of the 42 reported events were judged ‘probably related’ to the treatment; no serious adverse events were reported. Selective removal of monocytes and granulocytes from the blood in an extracorporeal circulation system was associated with clinical improvement in this small series of patients with SLE. Since this approach seems not to have the disadvantages of pharmacological immunosuppression, further controlled studies of Adacolumn cytapheresis are warranted in SLE.

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Adsorptive granulocyte/monocyte apheresis for the treatment of refractory rheumatoid arthritis: an open pilot multicentre trial

R Sanmartí 1S MarsalJ ValverdeE CasadoR LafuenteN KashiwagiJ-R Rodriguez-CrosA ErraD ReinaJ Gratacós Rheumatology (Oxford) 2005 Sep;44(9):1140-4. doi: 10.1093/rheumatology/keh701. Epub 2005 May 31.

Objective: To assess the efficacy and safety of adsorptive granulocyte and monocyte apheresis (GCAP) in patients with refractory rheumatoid arthritis (RA). Methods: Patients with active and refractory RA were treated with weekly GCAP sessions using a column filled with acetate beads (Adacolumn) over five consecutive weeks. Clinical assessments and response to therapy were analysed at weeks 5, 7, 12 and 20 in an open multicentre trial. The primary outcome measure of clinical response was 20% improvement in the American College of Rheumatology criteria (ACR20) at week 20. EULAR (European League Against Rheumatism) response criteria, based on the disease activity score for 28 joints (DAS28) and disability using the Health Assessment Questionnaire (HAQ), were also assessed. Results: Of 27 patients, 81.5% were women with mean disease duration of 14.4 yr. The mean number of previous disease-modifying antirheumatic drugs (DMARDs) was 3.7, and 48.1% of patients had previously failed on biologicals. On an intention-to-treat basis, 40.7% of patients achieved an ACR20 and 44.4% a therapeutic EULAR response at week 20. These percentages were 50 and 54.5% in 22 patients who completed the trial. In the 10 completers who had previously failed on biologicals, an ACR response was achieved in four patients (ACR20, two; ACR50, one; ACR70, one). A significant decrease was recorded in different ACR response components, including the tender joint and swollen joint counts, pain score and patient and physician global disease assessments, as well as the DAS28 index; most of them improved after week 5. ESR and CRP, but not the HAQ score, had decreased significantly at week 20. The treatment was well tolerated and only one serious adverse event related to the study procedure was documented (sepsis due to a catheter infection). Conclusions: GCAP treatment led to significant clinical improvement in a subset of patients with RA who had failed to respond to DMARDs or biologicals. Further large, placebo-controlled studies are warranted to fully assess the therapeutic value of GCAP for refractory RA.

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Effect of G-1 column (Adacolumn) therapy in rats with adjuvant arthritis on the migration and immunoreactivity of peripheral and splenic leukocytes

Satoru Nakazato 1Hiromichi TakaseYasuo YanagiharaThomas B IssekutzAndrew C IssekutzMasaaki TakaiMasahisa Kyogoku, Mod Rheumatol. 2005;15(4):249-57.

These results may be relevant to the rapid clinical anti-inflammatory effect observed in rheumatoid arthritis and possibly also in ulcerative colitis, without any pulmonary complications. In contrast, the adsorption rate by the G-1 column of T lymphocytes was very low, and their migration pattern to sites of dermal inflammatory reactions was not altered after treatment. However, the antigen (Mycobacterium purified protein derivative) reactivity of T lymphocytes in blood was almost completely abolished after G-1 column treatment of arthritic rats. This unexpected qualitative effect on T lymphocytes of G-1 treatment warrants further detailed study.

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