Nicolò Mezzina ¹, Sophia Elizabeth Campbell Davies ², Sandro Ardizzone ¹ Expert Opin Pharmacother 2018 Nov;19(16):1747-1757. doi: 10.1080/14656566.2018.1525361. Epub 2018 Sep 27.

Introduction: Treatment of ulcerative colitis (UC) is constantly evolving. In the last two decades, new therapeutic strategies have been implemented by addressing specific disease mechanisms: biological agents against tumor necrosis factor-α and integrins are now widely used, and more agents targeting different pathological pathways are being marketed. Despite these novel therapies, nonbiological drugs are still the mainstay of treatment, especially in mild-to-moderate disease, since a proven safety and tolerability profile is observed. Excellent efficacy both in induction and maintenance of remission is obtained, with a lower cost compared to biological agents. Areas covered: The purpose of this review is to summarize the current knowledge and the latest clinical evidence regarding nonbiological therapies for UC. Expert opinion: Concomitant administration of oral and rectal 5-aminosalicylates acid is more effective in the treatment of UC in remission. Corticosteroids are the treatment of choice in patients with moderately severe or severe UC. The association of azathioprine with biological treatments is more effective than monotherapy. Cyclosporine is an effective drug in severe UC, but its poor management must be considered. Probiotics are very popular; however, evidence on their actual role in UC still must be demonstrated; cytapheresis plays only a niche role at this time.

https://pubmed.ncbi.nlm.nih.gov/30220228/

https://www.tandfonline.com/doi/abs/10.1080/14656566.2018.1525361?journalCode=ieop20

Kengo Furuichi, Takashi Wada Contrib Nephrol  2018;196:188-193. doi: 10.1159/000485721. Epub 2018 Jul 24

Plasma exchange or double filtration plasmapheresis for rapidly progressive glomerulonephritis, and low-density lipoprotein (LDL) apheresis or leukocytapheresis for nephritic syndrome are two major apheresis therapies for kidney diseases. In addition to these apheresis therapies, plasma exchange for lupus nephritis or LDL apheresis for refractory focal segmental glomerulonephritis is clinically valuable and established. Although several possibilities of apheresis for kidney diseases were speculated in animal experiments or human studies, clinical applications have thus far been limited. In addition to clinical benefits of apheresis, reports revealed suggestive mechanisms of apheresis for the diseases. Moreover, these therapies would have a great potential for kidney diseases. Further studies are needed to establish the effectiveness of apheresis in kidney diseases in more depth.

Apheresis for Kidney Disease – PubMed (nih.gov)

Satoko Yamasaki ¹, Yasuhisa Sakata ², Hisako Yoshida ³, Sinpei Shirai ¹, Yuichiro Tanaka ¹, Ryo Nakano ¹, Takahiro Yukimoto ¹, Nanae Tsuruoka ¹, Ryo Shimoda ¹, Makoto Fukuda ¹, Motoaki Miyazono ¹, Yuji Ikeda ¹, Ryuichi Iwakiri ¹, Keizo Anzai ¹, Kazuma Fujimoto ¹ , Digestion. 2019;100(4):247-253.

Background: Leukocyte removal therapy (LRT) is an effective treatment for active ulcerative colitis (UC). The present study was performed to evaluate the relapse-free period after LRT and identify risk factors for relapse. Methods: In total, 94 patients who underwent first-time LRT for remission of moderate to severe UC from April 2004 to March 2016 were enrolled in the present study. The patients were randomly assigned to one of 2 treatments: leukocytapheresis (LCAP; n = 43) or granulocyte and monocyte/macrophage adsorptive apheresis (GMA; n = 51). The 5-year cumulative relapse-free rate and risk factors for relapse were evaluated. Results: The therapeutic response rate was 82% for GMA and 70% for LCAP without a statistically significant difference. The 5-year relapse-free rate was 34.7% in the LRT group. The 5-year relapse-free rate in patients aged > 40 years was 49.9%, which was significantly higher than that in patients aged ≤40 years (22.9%, p < 0.01). The relapse-free period was longer in the older than younger patients. The relapse-free period was longer in the ≥40- than <40-year-old patients (1,197 vs. 441 days, respectively; p = 0.03). Conclusions: The relapse-free period after LRT was examined in patients with UC, and 34.7% of patients achieved clinical remission within a 5-year period. The risk factor for early relapse after LRT was younger age. In conclusion, LRT might be a therapeutic option for maintenance of remission in patients with UC, especially patients aged ≥40 years.

https://pubmed.ncbi.nlm.nih.gov/30540999/

Helena Rolandsdotter ^1 2, Michael Eberhardson ^1 3, Ulrika L Fagerberg ^4 5, Yigael Finkel ^1 2 , J Pediatr Gastroenterol Nutr 2018 Jan;66(1):84-89.

Objective: The aim of the study was to analyze the effect of granulocyte and monocyte apheresis (GMA) with mesalazine for induction of remission in pediatric patients with newly onset chronic inflammatory bowel disease (IBD) colitis. Methods: Thirteen pediatric patients with newly onset extensive IBD colitis were investigated per the ECCO/ESPGHAN IBD protocol. Of these 13, 12 received 10 treatments with Adacolumn (ADA) during a median of 6.25 weeks in combination with low-to-moderate doses of mesalazine, which was continued after apheresis. A control colonoscopy was performed 12 to 16 weeks after GMA treatment. Primary outcomes were mucosal healing (Mayo endoscopic score) and histopathologic grading of biopsies. A secondary outcome was disease activity as measured by the Pediatric Ulcerative Colitis Activity Index. Results: Twelve children (6 girls) with a median age of 14.6 years and a median duration of symptoms at diagnosis of 3.2 months received all planned 10 treatment sessions with ADA. Ten of 12 patients had pancolitis and 2 of 12 extensive colitis. A final diagnosis, however, indicated ulcerative colitis in 10 children and Crohn disease in 2 children. At control colonoscopy, 8 of 12 children were in clinical remission and the Mayo endoscopic score showed significant improvement in 9 of 12 patients (P = 0.006). Complete microscopic remission, according to the Geboes score, was observed in 2 patients. Conclusions: In this small study GMA for induction of remission of newly onset pediatric IBD colitis was effective in 8 of 12 patients. Further controlled studies are warranted to confirm the efficacy of this treatment model.

https://pubmed.ncbi.nlm.nih.gov/28604509/

Iago Rodríguez-Lago ¹, José Manuel Benítez ², Valle García-Sánchez ², Ana Gutiérrez ³, Laura Sempere ⁴, Daniel Ginard ⁵, Manuel Barreiro-de Acosta ⁶, José Luis Cabriada ⁷ , Gastroenterol Hepatol. Aug-Sep 2018;41(7):423-431.

Granulocyte and monocyte apheresis is well tolerated and accepted by patients with IBD. Although we found no significant differences according to type of IBD or apheresis regimen, patient perception was affected by clinical effectiveness.

https://pubmed.ncbi.nlm.nih.gov/29739692/

Ziwei Huang ¹, Vikram Singh Raghuwanshi ¹, Gil Garnier ¹Front Bioeng Biotechnol. 2017 Jul 17:5:41. doi: 10.3389/fbioe.2017.00041

The functionality and aging mechanism of antibodies physisorbed onto cellulosic films was investigated. Blood grouping antibodies immunoglobulin G (IgG) and immunoglobulin M (IgM) were adsorbed onto smooth cellulose acetate (CAF) and regenerated cellulose (RCF) films. Cellulose films and adsorbed IgG layers were characterized at the air and liquid interface by X-ray and neutron reflectivity (NR), respectively. Cellulose film 208 Å thick (in air) swell to 386 Å once equilibrated in water. IgG adsorbs from solution onto cellulose as a partial layer 62 Å thick. IgG and IgM antibodies were adsorbed onto cellulose and cellulose acetate films, air dried, and aged at room temperature for periods up to 20 days. Antibody functionality and surface hydrophobicity were measured everyday with the size of red blood cell (RBC) agglutinates (using RBC specific to IgG/IgM) and the water droplet contact angle, respectively. The functionality of the aged IgG/IgM decreases faster if physisorbed on cellulose than on cellulose acetate and correlates to surface hydrophobicity. IgG physisorbed on RCF or CAF age better and remain functional longer than physisorbed IgM. We found a correlation between antibody stability and hydrogen bond formation ability of the system, evaluated from antibody carbonyl concentration and cellulosic surface hydroxyl concentration. Antibody physisorbs on cellulose by weak dipole forces and hydrogen bonds. Strong hydrogen bonding contributes to the physisorption of antibody on cellulose into a non-functional configuration in which the molecule relaxes by rotation of hydophobic groups toward the air interface.

Functionality of Immunoglobulin G and Immunoglobulin M Antibody Physisorbed on Cellulosic Films – PubMed (nih.gov)

Functionality of Immunoglobulin G and Immunoglobulin M Antibody Physisorbed on Cellulosic Films – PMC (nih.gov)

Cabriada, J.L., Rodríguez-Lago, I.

Enfermedad Inflamatoria Intestinal 20017 (16) 2, 62-69 DOI: 10.1016/j.eii.2016.12.001 

Granulocyte apheresis is a procedure that allows the removal of different activated leukocyte populations and it also modifies some circulating inflammatory mediators. These effects, along with its immunomodulatory potential, make it an attractive therapeutic option in inflammatory bowel disease. Previous studies with this technique have had significant limitations, but recent data is emerging about the ideal clinical setting in which granulocyte apheresis should be indicated. Most of the evidence supports its use in conditions that are dependent or refractory to corticosteroids, especially when treatments with immunomodulators or biologics has failed and when it is necessary to reduce or avoid the use of systemic corticosteroids. Its excellent safety profile gives it a role in cases of comorbidity or risk in the use of immunosuppressive drugs or in paediatric patients. In this review, we provide an update on the role of granulocyte apheresis in inflammatory bowel disease.

https://www.elsevier.es/es-revista-enfermedad-inflamatoria-intestinal-al-dia-220-articulo-granulocitoaferesis-2017-puesta-al-dia-S1696780116300999

Esteban Sáez-González ¹, Inés Moret ^2 3 4, Diego Alvarez-Sotomayor ², Francia Carolina Díaz-Jaime ², Elena Cerrillo ^2 3, Marisa Iborra ^2 3 4, Pilar Nos ^2 3 4, Belén Beltrán ^2 3 4 , Dig Dis Sci. 2017 Jun;62(6):1417-1425.

The benefit of cytapheresis appears to rest upon its ability to reduce levels of certain immune cell populations; however, whether this depletion results in further changes in lymphocyte populations and cytokine production needs further clarification. In this review, we aim to summarize existing evidence on the role of cytapheresis in patients with IBD, its effect on cytokine levels and cellular populations, and to discuss its potential impact on disease activity.

https://pubmed.ncbi.nlm.nih.gov/28432476/

Tetsuro Takayama ¹, Takanaori Kanai, Katsuyoshi Matsuoka, Susumu Okamoto, Tomohisa Sujino, Yohei Mikami, Tadakazu Hisamatsu, Tomoharu Yajima, Yasushi Iwao, Haruhiko Ogata, Toshifumi Hibi, J Crohns Colitis. 2013 Mar;7(2):e49-54.

Background: Although accumulating studies in Japan show that cytapheresis (CAP) therapy is safe and effective for the induction of remission of moderate or severe ulcerative colitis (UC), the long-term prognosis of UC patients treated with CAP is unknown. The aim of this study was to determine the long-term prognosis of UC patients treated with CAP. Methods: Ninety patients treated previously with CAP and followed for more than 3 years were evaluated. The rates of operation, readmission, and use or dose-up of corticosteroid were analyzed as long-term prognosis. Results: Following the first course of CAP treatment, 64% of patients showed clinical improvement (> 4-point decrease in the clinical activity index (CAI)), and 49% of patients achieved clinical remission (CAI ≤ 4). Longer disease duration and lower age at the first CAP treatment correlated significantly with the therapeutic effects of CAP (p = 0.003 and 0.035, respectively). The rates of operation and readmission were significantly lower in patients who showed previous clinical effects of CAP than in those who did not respond to CAP. The rates of operation and readmission were also significantly lower in patients whose treatment was combined with immunomodulators after the initiation of CAP than in patients who did not use immunomodulators. Importantly, the second course of CAP was also effective in most of the patients who showed a clinical response to the first CAP. Conclusions: Patients who achieve remission after the first CAP therapy may have a good long-term prognosis and a good response to a second CAP therapy even after relapse.

https://pubmed.ncbi.nlm.nih.gov/22633997/

https://academic.oup.com/ecco-jcc/article/7/2/e49/484944?login=false

The selective therapeutic apheresis procedures.

J. Clin. Apheresis 28:20–29, 2013  doi:10.1002/jca.21265 

Selective apheresis procedures have been developed to target specific molecules, antibodies, or cellular elements
in a variety of diseases. The advantage of the selective apheresis procedures over conventional therapeutic plasmapheresis is preservation of other essential plasma components such as albumin, immunoglobulins, and clotting
factors. These procedures are more commonly employed in Europe and Japan, and few are available in the
USA. Apheresis procedures discussed in this review include the various technologies available for low-density
lipoprotein (LDL) apheresis, double filtration plasmapheresis (DFPP), cryofiltration, immunoadsorption procedures, adsorption resins that process plasma, extracorporeal photopheresis, and leukocyte apheresis.

https://onlinelibrary.wiley.com/doi/abs/10.1002/jca.21265