Multiple Immunosuppressive Therapies Research Articles

Clinical Trials of Interferon Inhibitors in Systemic Lupus Erythematosus and Preliminary Real-World Efficacy of Anifrolumab.

Approval of anifrolumab for the treatment of moderate-to-severe systemic lupus erythematosus (SLE) in 2021 marked the success of a long quest to target the interferon system, in a disease wherein the latter has long been considered to play a pivotal role. Prior to anifrolumab, a number of agents had been tested in early phase clinical trials in patients with SLE, with equivocal results. Following its approval and marketing in several countries, the first reports regarding efficacy and safety in real-life clinical settings have been published, which suggest remarkable efficacy in skin manifestations of the disease, even after prior failure to multiple immunosuppressive therapies. In this report, we provide a short overview of IFN inhibitors that have been used in clinical trials of SLE, with a focus on anifrolumab; we also review all available evidence to date regarding its real-world efficacy and safety.

Progressive multifocal leukoencephalopathy associated with systemic lupus erythematosus: longitudinal observation of lymphocytes, JC virus in cerebrospinal fluid, and brain magnetic resonance imaging

Progressive multifocal leukoencephalopathy (PML) rarely occurs in patients with systemic lupus erythematosus (SLE). This report presents the case of a patient who developed PML due to SLE-associated multiple factors. A 60-year-old woman diagnosed with SLE undergoing multiple immunosuppressive therapies, including azathioprine, presented with cerebral cortical symptoms, lymphocytopenia, and vitamin B12 deficiency and was subsequently diagnosed with SLE-associated PML. We evaluated the cause and disease activity of PML, focusing on the longitudinal assessment of lymphocytopenia, JC virus (JCV) DNA copy number in the cerebrospinal fluid, and magnetic resonance imaging (MRI) findings. Discontinuing azathioprine and initiating alternative immunosuppressive treatments with intramuscular vitamin B12 injections affected lymphocytopenia and disease management. However, despite recovery from lymphopenia and JCV DNA copy number being low, the large hyperintense and punctate lesions observed on the fluid-attenuated inversion recovery (FLAIR) images exhibited varying behaviors, indicating that the balance between contributing factors for PML may have fluctuated after the initial treatment. Clinicians should be meticulous when assessing the underlying pathology of the multifactorial causes of PML due to SLE. The difference in the transition pattern of these lesions on FLAIR images may be one of the characteristics of MRI findings in PML associated with SLE, reflecting fluctuations in disease activity and the progression stage of PML.

Population pharmacokinetics of everolimus in renal transplant recipients receiving long-term multiple immunosuppressive therapy

Everolimus is used for immunosuppression after renal transplantation. This study aimed to develop a population pharmacokinetic (PopPK) model of everolimus using therapeutic drug monitoring (TDM) data of patients under long-term multiple immunosuppressive therapy, including tacrolimus. To develop the model, 185 renal transplant recipients with 3358 everolimus blood concentrations during a median postoperative period of 35.3 months were included. The PopPK model is described as a one-compartment model with first-order absorption. The population mean of apparent clearance is 8.92 L/h (relative standard error = 3.6%), and this negatively correlated with the dose-normalized concentration (C/D) of tacrolimus and hematocrit value, and positively correlated with a daily dose of everolimus (i.e. TDM effect). The usefulness of dose adjustment using the final popPK model was assessed by a simulation study. The ratio of the first trough measurement within the therapeutic range of 3–8 ng/mL increased from 69.8% in the original dose to 87.9% in the individual dose calculated by the final PopPK model. The tacrolimus C/D ratio before initiating everolimus therapy and the hematocrit value were useful to estimate the initial dose of everolimus and can improve the safety and effectiveness of immunosuppressive therapy involving everolimus.

Investigation of optimal hernia repair techniques in patients with inflammatory bowel disease.

Multiple laparotomies, immunosuppressive therapy, wound infection, and malnutrition are risk factors for incisional hernia development, which places inflammatory bowel disease (IBD) patients at high risk. With advances in minimally invasive techniques, this study assesses incisional hernia repair techniques and complications in the IBD population. A single-center, retrospective review of adults with IBD who underwent incisional hernia repair from 2008 to 2022. Complications relative to operative approach and mesh placement location were assessed using descriptive and univariate statistics. Eighty-eight IBD patients underwent incisional hernia repair. Fifty-two (59.1%) were on immunomodulators and 30 (34.1%) were repaired primarily. Thirty-five (39.7%) hernias recurred, of whom 19 (33%) had mesh placed. Three (30%) occurred in onlay repairs and 16 (33%) occurred in underlay repairs. Subdivision of underlay repairs into intraperitoneal, preperitoneal and retrorectus mesh placement revealed recurrence rates of 35.1%, 50%, and 14.3%, respectively. Patients with open repair were more likely to have intraoperative bowel injury (28.6% vs 9.7%, p = 0.041) and develop postoperative seromas/abscesses (12.5% vs 0%, p = 0.001) and wound complications (17.9% vs 0%, p = 0.012) compared to laparoscopic. Seromas/abscesses developed more frequently in onlay repairs compared to underlay (40% vs 2.13%, p = 0.001). Twelve (13.6%) patients presented with postoperative small bowel obstruction (SBO), 7 (58.3%) of whom had mesh placed, and 6 (85.7%) were underlay. All SBO after underlay repair had intraperitoneally placed mesh. When comparing surgeons, hernias were more likely to recur performed by colorectal surgeons compared to hernia surgeons (63.3% vs 21.3%, p < 0.001). In IBD patients, minimally invasive approaches lead to fewer perioperative complications compared to open. Underlay mesh placement demonstrated decreased incidence of seroma/abscess formation compared to onlay. When sub-grouped, underlay placements were similar in terms of complications. Retrorectus placement, however, had fewer recurrences and no readmissions for SBO. This suggests a minimally invasive approach or placement of retrorectus mesh may provide the optimal repair in this patient population.

Characterization of AR-CGD female patient with a novel homozygous deletion in CYBC1 gene presenting with unusual clinical phenotype

Chronic granulomatous disease (CGD) is a human IEI caused by mutations in genes encoding the NADPH oxidase subunits, the enzyme responsible for the respiratory burst. CGD patients have severe life-threatening infections, hyperinflammation and immune dysregulation. Recently, an additional autosomal recessive AR-CGD (type 5) caused by mutations in CYBC1/EROS gene was identified.We report a AR-CGD5 patient with a novel loss of function (LOF) homozygous deletion c.8_7del in the CYBC1 gene including the initiation ATG codon that leads to failure of CYBC1/EROS protein expression and presenting with an unusual clinical manifestation of childhood-onset sarcoidosis-like disease requiring multiple immunosuppressive therapies. We described an abnormal gp91phox protein expression/function in the patient's neutrophils and monocytes (about 50%) and a severely compromised B cell subset (gp91phox < 15%; DHR+ < 4%).Our case-report emphasized the importance of considering a diagnosis of AR-CGD5 deficiency even in absence of typical clinical and laboratory findings.

A Case of Anti-MDA5 Antibody-positive Dermatomyositis with Interstitial Lung Disease Successfully Treated with Multiple Immunosuppressive Therapy at an Early Stage

50 歳，女性。初診の約 2 週間前に手指の痺れと上肢の筋力低下を自覚し，前医を受診した。手指屈側に鉄棒豆様皮疹を認め，皮膚筋炎を疑われた。胸部 CT にて間質性肺炎像を認めたため紹介となった。当科初診時，筋酵素の上昇や画像上筋炎所見は認めず，無筋症性皮膚筋炎と診断した。初診 8 日後に入院し，同時に抗 MDA5 抗体陽性と判明したため，プレドニゾロン（1 mg/kg/day），タクロリムス，シクロホスファミド大量静注療法（IVCY）を導入した。治療後肺炎像は消失し，IVCY は 3 クールで終了し退院とした。その後外来にてプレドニゾロン漸減中だが，再燃を認めていない。抗 MDA5 抗体陽性皮膚筋炎は，急速進行性肺炎を併発し予後不良であることが知られている。自験例は早期に多剤併用免疫抑制療法を行うことにより，病状の進行を抑制し得たと考えられた。

De Novo Inflammatory Bowel Disease Rarely Occurs During Posttransplant Immunosuppression.

De novo chronic idiopathic inflammatory bowel disease (CIIBD) is reported to occur at higher rates in posttransplant patients than that of the general population. The previous reports, however, included patients with primary sclerosing cholangitis (PSC), a known association with CIIBD. Hence, we investigated how often posttransplant de novo CIIBD occurs in the absence of PSC. We identified 185 posttransplant adults without a history of PSC or CIIBD, who had undergone colonoscopy between July 2013 and June 2020. Biopsies were reviewed and clinical data were gathered. CIIBD-like colitis accounted for 1.1% (2/185) of our cohort. The 2 affected patients were already taking multiple immunosuppressive therapies. They were initially placed on standard CIIBD maintenance therapy, but then required escalation therapy. One patient had persistent active colitis despite escalation therapy, while the other subsequently had resolution of symptoms and developed quiescent disease. The incidence of CIIBD-like colitis in our study population was lower than what has been previously described. Both patients had a poor response to standard CIIBD therapy, raising the question whether their diagnosis is truly de novo CIIBD or another immunologic process.

Narrative review of the relationship between COVID-19 and PJP: does it represent coinfection or colonization?

BackgroundPneumocystis jirovecii (P. jirovecii) is increasingly identified on lower respiratory tract specimens of COVID-19 patients. Our narrative review aims to determine whether the diagnosis of pneumocystis jirovecii pneumonia (PJP) in COVID-19 patients represents coinfection or colonization based on the evidence available in the literature. We also discuss the decision to treat COVID-19 patients with coinfection by PJP. MethodsA literature search was performed through the Pubmed and Web of Science databases from inception to March 10, 2021.ResultsWe identified 12 COVID-19 patients suspected to have PJP coinfection. All patients were critically ill and required mechanical ventilation. Many were immunosuppressed from HIV or long-term corticosteroids and other immunosuppressive agents. In both the HIV and non-HIV groups, severe lymphocytopenia was encountered with absolute lymphocyte and CD4+T cell count less than 900 and 200 cells/mm, respectively. The time to PJP diagnosis from the initial presentation was 7.8 (range 2–21) days. Serum lactate dehydrogenase and beta-D-glucan were elevated in those coinfected with PJP. All patients were treated with anti-PJP therapy, predominantly sulfamethoxazole-trimethoprim with corticosteroids. The overall mortality rate was 41.6%, and comparable for both HIV and non-HIV groups. ConclusionAs the current evidence is restricted to case reports, the true incidence, risk factors, and prognosis of COVID-19 patients with PJP coinfections cannot be accurately determined. Comorbidities of poorly controlled HIV with lymphocytopenia and multiple immunosuppressive therapies are likely predisposing factors for PJP coinfection.

Skin and mucosa in patients with solid organ transplant: risks and precautions

In solid organ transplant patients; many skin diseases are more common and more resistant to treatment, because of the multiple medications and immunosuppressive therapies. In order to increase survival, it is important to evaluate and follow these patients with a multidisciplinary team including the dermatologist. In this review, the following are reviewed along with the current literature; skin and mucosa findings due to immunosuppressive therapies used in solid organ transplant patients, inflammatory, infectious and neoplastic skin diseases which are increased compared to the normal population, and the important points in diagnosis and treatment of these diseases.

Prosthetic temporomandibular joint reconstruction in a cohort of adolescent females with juvenile idiopathic arthritis

BackgroundTemporomandibular joint (TMJ) arthritis and involvement is commonly seen in Juvenile Idiopathic Arthritis (JIA). Therapy includes conservative measures, but also includes intraarticular corticosteroid injections (IASI) and systemic immunosuppressive therapy. Despite aggressive medical therapy, some patients develop arthritic changes and frank TMJ ankylosis that can result in persistent pain and limitation in range of motion (ROM). A surgical option is prosthetic TMJ replacement with concurrent correction of dentofacial deformities, which can be performed simultaneously. The objective of this study was to evaluate the outcomes of prosthetic TMJ replacement in a cohort of adolescent females with JIA and severe TMJ involvement.MethodsThis is a retrospective case series that took place at one tertiary care center. Patients with a diagnosis of JIA who also underwent alloplastic TMJ replacement were identified through electronic medical record system (EMR) and reviewed. Chart review included analysis of all documents in the EMR, including demographic data, JIA history, surgical complications, ROM of TMJ measured by maximal incisal opening in millimeters (mm) and TMJ pain scores (4-point Likert scale: none, mild, moderate, severe) obtained pre- and postoperatively.ResultsFive female patients, ages 15–17 year when TMJ replacement was performed, had nine total joints replaced with a post-operative follow-up period of 12–30 months. All patients had polyarticular, seronegative JIA and were treated with IASI and multiple immunosuppressive therapies without resolution of TMJ symptoms. One patient had bilateral TMJ ankylosis. Three of the five patients demonstrated significant dentofacial deformities, and all underwent simultaneous or staged orthognathic surgery. All patients had improvement in TMJ pain with most (80%) reporting no pain, and all had similar or improved ROM of their TMJ postoperatively. There was one delayed postoperative infection with Cutibacterium Acnes that presented 15 months after surgery and required removal and reimplantation of prosthesis.ConclusionThe sequelae of TMJ arthritis and involvement from JIA in the adolescent population can be difficult to treat. Current medical therapy can be successful, however, in select cases that develop chronic changes in the TMJ despite extensive medical therapy, early results show that prosthetic joint replacement maybe a reasonable surgical option. With prosthetic joint replacement pain levels were reduced and range of motion was maintained or improved for all patients.

A Review of Drug-Drug Interactions for Biologic Drugs Used in the Treatment of Psoriasis

To provide an overview of reported drug interactions between biologic drugs and concomitant therapies. Reports of potential drug interactions were compiled through a search of Micromedex, drug monographs (Canadian, American, and European), as well as a PubMed search of each biologic drug with the term "drug interaction." Generally, caution should be exercised when multiple immunosuppressive therapies are prescribed due to increased risk of infection. However, this is more the result of a synergistic effect as opposed to a true drug interaction. There have been cases where multiple biologic therapies have been concomitantly used without adverse events, as their mechanisms involved different pathways. The sources used to compile this guide were often comprised of low levels of evidence, reinforcing the idea that further studies are required to better direct prescribers.

A survey of extracorporeal photopheresis treatment in pediatric patients in the United Kingdom.

Extracorporeal photopheresis (ECP) is a second‐line therapy in acute and chronic GVHD and solid organ transplant rejection. We report ECP use in 98 pediatric patients in seven UK centers from 2010 to 2017, the majority treated for aGVHD (73.5%). ECP was safe and well tolerated including in low body weight patients. Most patients were on multiple immunosuppressive therapies prior to ECP; 45.9% were able to reduce or stop immunosuppression with treatment. Complete or partial response was reported in almost 60%. This study supports the need to include ECP treatment data to national transplant databases to provide accurate information regarding service provision, patient outcomes, and safety.

Efficacy of therapeutic plasma exchange in a patient with coagulation inhibitors (acquired haemophilia A) – A case report

Acquired haemophilia A (AHA) is a rare disorder with mostly idiopathic aetiology that leads to factor VIII (FVIII) deficiency due to coagulation inhibitors formation. Treatment protocol includes immunosuppression and Factor VIII bypassing agents including activated Prothrombin Complex Concentrates (PCC). Nevertheless, the role of plasma exchange is not clear in the treatment of AHA. We report a case of 73 year old male who presented with haematuria, prolonged activated partial thromboplastin time (APTT) and a very high titres of Factor VIII inhibitors of 98 Bethesda units (BU) and was diagnosed with acquired haemophilia A. He failed to respond to multiple immunosuppressive therapies including rituximab. Therefore, therapeutic plasma exchange (TPE) therapy was planned due to persistence of haematuria despite immunosuppressive therapies. After five cycles of plasma exchange, APTT became normal, haematuria subsided and Factor VIII inhibitors became negative. Patient was discharged without any bleeding and in a stable condition. In this index case, plasma exchange played a very crucial role, resulting in recovery of the patient. These results advocate that therapeutic plasma exchange is an effective therapy for acquired haemophilia A.

Fast CMV and EBV Reactivations after Ruxolitinib for Graft-Versus-Host Disease Treatment

Introduction: Corticosteroid-refractory graft-versus-host disease (GVHD) remains a serious complication of hematopoietic stem cell transplantation (HSCT) with high morbidity and mortality rates. Unfortunately, no standard therapy exists for this setting. Ruxolitinib (ruxo), an oral selective Janus-associated kinase (JAK) inhibitor, achieved good results for corticoresistant acute and chronic GVHD in preclinical and clinical studies, with 80% overall response rates. Recent studies showed an increased risk of infections in patients treated with ruxo, especially Epstein-Barr virus (EBV) and cytomegalovirus (CMV) reactivations. Patients and methods: In order to assess the efficacy and the safety of ruxo, we reviewed here the outcome of 57 patients who received ruxo for corticosteroid-refractory GVHD (in case of digestive tract involvement or in the absence of available ongoing clinical trials) or as a steroids-sparing medication. EBV and CMV reactivation risks were also assessed in the 137 consecutive patients received HSCT between January 1, 2012 and December 31, 2017 and who presented acute or chonic GVHD (57 of whom received ruxo). For this purpose, each reactivation were analyzed separately as a competing risk with death in a cause specific Cox model of survival after the first GVHD occurrence and the onset of ruxo therapy was coded as time dependent covariate. Results: The median age of 57 patients with ruxo was 55 years (range, 49 to 61). Indication for HSCT was acute myeloid leukemia for 25% patients, lymphoma for 30%, acute lymphoblastic leukemia for 11%, myeloproliferative neoplasm for 14% and myelodysplastic syndrome for 7%. Only 9% of this patients received ruxo before HSCT. Unrelated donor was used for 60% patients and main source of hematopoietic stem cells was peripheral stem cells (93%). T cell depletion with polyclonal anti-thymocyte globulin was performed for 89% of patients. Conditioning with high doses cyclophosphamide was used for 21% patients. A lymphopenia &lt;1G/L persisted at day 100 for 42/51 patients evaluated. In these 57 patients, ruxo was given for 62 episode of GVHD (acute: 21 [which 95% for an acute grade III-IV GVHD]; chronic: 36; overlap syndrome: 5). Response rates to ruxo were 48% for acute GVHD, 60% for overlap syndrom and 58% for chronic GVHD. The overall GVHD related-death rate was 33% (19% for acute GVHD and 14% for chronic GVHD). Our median follow-up was 30 months (range, 9 to 42) after HSCT. Main non-infectious adverse events were cytopenias (17/57) and hepatic cytolysis (6/57) leading to discontinuation or tapering of ruxo in 12 patients. EBV reactivation (&gt; 4 log or increasing viral charge of 0.5 log) occurred in 19 patients after ruxo with a 6-weeks cumulative incidence (6WCuI) of 22% (95CI [95% confidence interval]: 15-34). It was the first reactivation in 13 patients. CMV reactivation (&gt; 3 log) occurred in 8 patients after ruxo with a 6WCuI of 4% (95CI: 7-25). It was the first reactivation in 3 patients (Figure 1). The distribution of first reactivation before ruxo and in the remaining 80 patients is shown in Table 1. Thus, 6WCuI of first EBV and CMV reactivation after the first episode of GVHD was 24% (95CI: 19-31) and 20% (95CI: 15-25) respectively. Finally, onset of ruxo coded as time dependent covariates retained a significant adverse prognostic value for the competing risks of death and first episode of EBV reactivation (HR [Hazard Ratio]: 2,657, p&lt;0,05) as well as first episode of CMV reactivation (HR: 1,747, p&lt;0,05) after first episode of GVHD. Discussion /Conclusion: Ruxo initiation coded as a time-dependent covariate was significantly associated with the overall risk of viral reactivation after the first episode of GVHD and the viral reactivations incidences after ruxo were similar with the incidence of reactivation at the onset of GVHD. Thus, it might be linked to the immuno-compromised state induced by both HSCT and GVHD. Furthermore, as we used ruxo for serious gastro intestinal GVHD, we could have selected patients with a more severe GVHD, requiring multiple immunosuppressive therapy, worsening immune reconstitution. To our knowledge it is the first study to assess the competing risk of CMV and EBV reactivation during ruxo treatment for GVHD. Given its effectiveness in corticoresistant GVHD, ruxo use must not be limited by the fear of viral reactivation at the light of our data, conditioned upon a close monitoring of viral loads in the first weeks. Disclosures No relevant conflicts of interest to declare.

Prevalence of cervical HPV infection in women with systemic lupus erythematosus: A systematic review and meta-analysis.

The objectives of this systematic review and meta-regression were: 1) to compare the prevalence of cervical HPV infection between SLE patients and healthy controls and 2) to evaluate the relationship between cervical HPV infection and traditional and SLE-related risk factors for cervical HPV infection in these patients. We conducted a systematic literature review (PubMed, Cochrane Library, Embase, Virtual Health Library and SciELO databases) following PRISMA guidelines and using meta-regression to investigate the pooled prevalence of cervical HPV infection in adult women with SLE. The articles included were independently evaluated by two investigators who extracted information on study characteristics, defined outcomes, risk of bias and summarized strength of evidence [Quality of evidence using the Oxford Centre for evidence-based medicine (EBM) Levels of Evidence]. Using meta-regression, we further analyzed whether factors such as multiple sexual partners and immunosuppressive therapy were associated with HPV prevalence. We evaluated the quality of evidence included using the Oxford Centre for EBM levels of evidence. Pooled odds ratios (ORs) and 95% confidence intervals (CI) were calculated for studies providing data on HPV prevalence in women with SLE and in healthy controls. A total of 687 articles were identified; 9 full-text articles examining the prevalence of cervical HPV infection in SLE women were included, comprising 751 SLE women. Eight studies employed PCR using general primers. The HPV prevalence varied from 3.1% to 80.7%. In the random effects meta-analysis, the pooled prevalence of cervical HPV infection in SLE vs. controls was 34.15% (95% CI: 19.6%-52.5%) vs. 15.3% (95% CI 0.79-27.8%), OR = 2.87 (95% CI: 2.20-3.76) p < .0001, with large between-study heterogeneity (I2 = 95.4%). When only SLE women were evaluated, meta-regression showed no significant differences between patients with and without a background of multiple sexual partners and any immunosuppressive therapy. In addition, the prevalence of cervical HPV infection did not significantly differ between SLE patients on azathioprine or cyclophosphamide. This meta-analysis suggests that the prevalence of cervical HPV infection is higher in SLE women than in healthy controls. However, multiple sexual partners and any immunosuppressive therapy or specific immunosuppressive treatment (azathioprine and cyclophosphamide) were not associated with the prevalence of cervical HPV infection.

Toxic myopathies.

Our aim is to highlight major advances reported in the last few years in drug-induced muscle toxicity. Our focus is on myopathies induced by statins and immune checkpoint inhibitors with a brief overview of rare steroid myopathies. Statin muscle injury is frequently because of direct toxicity rather than an autoimmune mechanism. Laboratory testing and muscle pathologic features distinguish these two conditions. Statin-associated necrotizing autoimmune myopathy (SANAM) is associated with an autoantibody in 66% of cases targeting the HMGCR enzyme. The later autoantibody is a marker for necrotizing autoimmune myopathy, regardless of statin exposure. In SANAM, MHC-I antigens are expressed on the surface of intact muscle fibers. Genetic HLA loci predispose patients exposed to statins to immunologic toxicity. SANAM requires long-term therapy with multiple immunosuppressive therapies. Immune checkpoint inhibitors are powerful emerging therapies for advanced cancer that pause a novel therapeutic challenge. This review is focused on statins, the most prevalent myotoxic drug class. In addition, we examine the accumulating body of evidence of muscle injury and its management with immune checkpoint inhibitors. We anticipate the reader to become more knowledgeable in recent discoveries related to these myotoxic drugs, and their mechanisms of action and management.

The need for better preventative strategies for inflammatory bowel disease patients at risk of herpes zoster virus.

Immunosuppressed inflammatory bowel disease (IBD) patients have an increased risk of herpes zoster virus (HZV) infection. The existing live-attenuated HZV vaccine is contraindicated in some of these patients and can only be used with caution in others. To describe characteristics of IBD patients suffering HZV to enable implementation of risk mitigation strategies for those at highest risk. Gastroenterologists completed a proforma for IBD patients who experienced HZV infection: IBD phenotype, details of HZV infection, immunosuppression and any change to treatment upon diagnosis of HZV. A total of 30 cases was identified: Crohn disease (CD) (n = 25) and ulcerative colitis (n = 5). In total, 80% (20/25) of the CD patients had penetrating, stricturing or perianal disease. Time from commencement of immunosuppression to HZV infection was highly variable (range: 3 months to over 10 years). A total of 90% (27/30) of patients was on at least one immunosuppressive therapy; of those, one-third was on monotherapy (9/27) and two-thirds (18/27) on dual therapy. A total of 89% (24/27) of immunosupressed patients was on a thiopurine (monotherapy; 6/27) or in combination (18/27). Complications of HZV occurred in 27% (8/30) of patients. Our series is consistent with existing epidemiological analysis that identified more severe IBD and the use of multiple immunosuppressive therapies as risk factors for HZV. If the promise of an investigational subunit HZV vaccine is realised in immunocompromised patients, better protection may be possible in the future. Thiopurine medications were the most commonly used immunosuppressant in this series. Age and duration of immunosuppressive therapy do not appear to predict HZV infection.

Anti-TNF Exposure Is Not Associated With Increased Post-Operative Morbidity or Reoperation Among Crohnʼs Disease Patients

Introduction: For Crohn's disease (CD) patients, surgical intervention is frequently recommended, often after trials of multiple immunosuppressive medical therapies have proven ineffective at controlling symptoms or disease activity. However, the evidence regarding the impact of immunosuppression on operative morbidity is equivocal. The aim of this study was to determine if recent anti-tumor necrosis factor-alpha (anti-TNF) exposure negatively impacts outcomes following bowel resection surgery in a modern cohort of CD patients. Methods: We performed a cohort study of individuals with CD presenting to a tertiary inflammatory bowel disease referral center for ileocolonic resection (ICR) over a 5-year period (2011-2015). The electronic health record was analyzed and data collected on preoperative medications, disease behavior, smoking status, and perioperative/postoperative morbidity. Results: 73 CD patients underwent ICR from 2011-2015 (40 male, 33 female), with mean age of 38.3 ± 1.93 years at the time of surgery. 21% (n=15) of all surgeries were emergent and mean hospital length of stay (LOS) was 8.9 ± 0.5 days. 39 patients (53.4%) had recent anti-TNF exposure (last dose within 60 days of surgery) (Figure 1), with 76.7% actively using anti-TNFs at the time of surgery. Compared to naïve patients, anti-TNF exposure preoperatively was not associated with increased medical or surgical postoperative morbidity, LOS, or reoperation (Figure 2). Anti-TNF exposed patients preoperatively were more likely to be treated with anti-TNFs following surgery compared to naïve patients (82.1% vs 40.6%, p=0.0005). Naïve patients were more likely to be on no medications postoperatively compared to exposed patients (37.5% vs 10.3%, p=0.01). Anti-TNF exposed patients were also more likely to be in endoscopic remission on postoperative colonoscopy compared to anti-TNF naïve patients (91.3% vs 65.4%, p=0.04) (Figure 3).FigureFigureFigureConclusion: Anti-TNF use preoperatively was not associated with increased postoperative morbidity (medical or surgical) or reoperation. The anti-TNF treated patients were more likely to resume treatment postoperatively with a significantly higher rate of endoscopic remission on follow-up colonoscopy. These findings suggest that surgery should not be delayed due to recent exposure to anti-TNF, and that these anti-TNF exposed patients have a favorable immediate postoperative course and sustained outcomes with resuming treatment after surgery.

P.069 Vaccination protocol for MS patients undergoing immunosuppressive therapy: an important topic lacking consensus

Background: As therapy for MS has expanded to include multiple immunomodulatory and immunosuppressive therapies, the need to consider patient vaccination status has emerged as a salient issue in the treatment of MS. Unfortunately, there is little research or consensus about how vaccination in these patients should be addressed. Methods: A search of primary literature on the topic of potential pathogens and available vaccinations in immunosuppressed patients was performed. We reviewed the limited available information in the MS, gastroenterology, and rheumatology literature. As well, the current Canadian immunization guide was referred to along with expert opinion from public health nurses and infectious disease specialists. Results: There is currently little consensus about vaccination protocols for patients initiating immunosuppressive therapy. We integrated information from all of our sources to create a preliminary protocol for the vaccination of MS patients prior to initiation of immunosuppressive therapy. Conclusions: More work needs to be done to create standardized vaccination protocols for MS patients who will be undergoing immunosuppressive therapy. We have created a preliminary protocol in conjunction with public health to standardize the vaccinations that MS patients receive. We hope that this will streamline immunization of patients immediately after diagnosis of MS so that initiation of immunosuppressive therapy will not be delayed in the future.

Systemic Treatment for Noninfectious Intraocular Inflammation

Although uncommon, uveitis and other ocular inflammatory disorders may pose a serious threat to a patient’s vision and quality of life. The purpose of this review is to evaluate the indications for immunosuppressive therapy in the treatment of uveitis and to appraise the data regarding their usage, including efficacy and potential side effects. While some agents such as antimetabolites have been used to treat uveitis for decades, there are now newer medications such as biologics that have recently met with great success. Adalimumab is the first biologic therapy FDA approved for the treatment of uveitis. There are multiple immunosuppressive therapies available for the treatment of uveitis that allow for sustained control of ocular inflammation and limitation of systemic corticosteroid exposure. Additional research will be necessary to characterize the efficacy of newer agents to determine if they may be superior and tolerated as older therapies.