CRP and sCD25 help distinguish between adult-onset Still's disease and HLH.

OBJECTIVE: Adult-onset Still's disease (AOSD) and secondary hemophagocytic lymphohistiocytosis (sHLH) are both hyperferritinemic cytokine storm syndromes that can be difficult to distinguish from each other in hospitalized patients. The objective of this study was to compare the inflammatory markers ferritin, D-dimer, C-reactive protein (CRP), and soluble CD25 (sCD25) in patients with AOSD and sHLH. These four markers were chosen as they are widely available and represent different aspects of inflammatory diseases: macrophage activation (ferritin); endothelialopathy (D-dimer); interleukin-1/interleukin-6/tumour necrosis factor elevation (CRP) and T cell activation (sCD25). METHODS: This was a single-center retrospective study. Patients diagnosed by the Hematology service at Vancouver General Hospital for AOSD or sHLH from 2009 to 2023 were included. RESULTS: There were 16 AOSD and 44 sHLH patients identified. Ferritin was lower in AOSD than HLH (median 11 360 µg/L vs. 29 020 µg/L, p = .01) while D-dimer was not significantly different (median 5310 mg/L FEU vs. 7000 mg/L FEU, p = .3). CRP was higher (median 168 mg/L vs. 71 mg/L, p <.01) and sCD25 was lower (median 2220 vs. 7280 U/mL, p = .004) in AOSD compared to HLH. The combined ROC curve using CRP >130 mg/L and sCD25< 3900 U/mL to distinguish AOSD from HLH had an area under the curve (AUC) of 0.94 (95% confidence interval 0.93-0.97) with sensitivity 91% and specificity 93%. CONCLUSIONS: These findings suggest that simple, widely available laboratory tests such as CRP and sCD25 can help clinicians distinguish AOSD from HLH in acutely ill adults with extreme hyperferritinemia. Larger studies examining a wider range of clinically available inflammatory biomarkers in a more diverse set of cytokine storm syndromes are warranted.

The association between cannabis and codeine use: a nationally representative cross-sectional study in Canada.

BACKGROUND: Due to the growing use of cannabis for the purposes of pain relief, evidence is needed on the impact of cannabis use on concurrent analgesic use. Therefore, our objective was to evaluate the association between the use of cannabis and codeine. METHODS: We conducted a cross-sectional study using data from the nationally representative Canadian Tobacco, Alcohol and Drugs Survey (2017). The primary explanatory variable was self-reported use of cannabis within the past year. The outcome was the use of codeine-containing product(s) within the past year. We used multivariable binomial logistic regression models. RESULTS: Our study sample comprised 15,459 respondents including 3338 individuals who reported cannabis use within the past year of whom 955 (36.2%) used it for medical purposes. Among individuals who reported cannabis use, the majority were male (N = 1833, 62.2%). Self-reported use of cannabis was associated with codeine use (adjusted odds ratio [aOR] 1.89, 95% CI 1.36 to 2.62). Additionally, when limited to cannabis users only, we found people who used cannabis for medical purposes to be three times more likely to also report codeine use (adjusted odds ratio [aOR] 2.96, 95% CI 1.72 to 5.09). DISCUSSION: The use of cannabis was associated with increased odds of codeine use, especially among individuals who used it for medical purposes. Our findings suggest a potential role for healthcare providers to be aware of or monitor patients' use of cannabis, as the long-term adverse events associated with concurrent cannabis and opioid use remain unknown.

Rheumatology health care providers' views and practices on obesity and smoking cessation management in rheumatoid arthritis.

OBJECTIVE: To assess rheumatology health care providers' (HCPs) knowledge, beliefs, self-efficacy, practices, and perceived barriers pertaining to weight management and smoking cessation counselling in patients with rheumatoid arthritis (RA). METHOD: We administered an online survey to collect self-reported data on rheumatology HCPs' knowledge, beliefs, self-efficacy, perceived barriers, and practices related to weight management and smoking cessation counselling. Participants were recruited through invitation emails (with anonymous survey links) sent by three Canadian rheumatology organizations. RESULTS: Fifty-nine rheumatology HCPs (15 nurses, 44 physicians) completed the survey (response rate: 11%). Over 85% correctly identified associations between obesity, or smoking, and more severe or active RA, as well as poorer response to treatment. All but one participant agreed that it was part of their responsibility to discuss these issues with patients, but 78% (46/59) felt not or slightly confident in their ability to help patients quit smoking or achieve clinically significant weight loss. The majority did not routinely assist patients in accessing appropriate resources or providers (only 42% did for obesity, 36% for smoking), send referrals (2-44%, depending on referral), or offer relevant educational materials (15% for obesity, 20% for smoking). Common barriers included competing demands and lack of time, training, access to expertise, and knowledge of available programs. CONCLUSION: Most rheumatology HCPs understood the implications of cigarette smoking and obesity in RA and accepted responsibility in addressing these issues. However, they lacked the time, training, confidence, and knowledge of local resources to do so effectively. There is a need to bridge this gap. Key Points • Training through medical and nursing school as well as residency on weight management and smoking cessation counselling was nearly unanimously described as poor or fair. • Most rheumatology health care providers understood the implications of cigarette smoking and obesity in rheumatoid arthritis and accepted responsibility in addressing these issues; however, they lacked the time, training, confidence, and knowledge of local resources to do so effectively. • There is a need to bridge the gap between health care providers' intentions and actions, and this may include the development of guides outlining local weight management and smoking cessation expertise, programs, referral processes, and educational materials.

Clinical spectrum and therapeutics in Canadian patients with anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis: a case-based review.

The objective of the study was to determine the clinical features and treatment course in Canadian patients with dermatomyositis (DM) associated with the anti-melanoma differentiation-associated gene 5 antibody (MDA5). A retrospective chart review of consecutive patients with anti-MDA5 antibody DM from two Canadian tertiary care centre between 2014 and 2018 was done. Twenty-one consecutive cases of anti-MDA5-positive DM were identified. Median age at diagnosis was 52 years, 71% Asians, predominantly Chinese, and 29% Caucasians. In this case series, all patients had either typical DM rash, or vasculopathy and ulceration unique to anti-MDA5-positive DM. 38% of the patients had rapid progressive (RP)-interstitial lung disease (RP-ILD), 33% had chronic ILD and 29% had asymptomatic ILD. Anti-Ro52 positivity was more prevalent in RP-ILD. Mortality was high in the RP-ILD group, with five deaths in eight patients. Lung transplant was life-saving intervention for three of the RP-ILD patients who survived. A review of the literature in treating RP-ILD associated with anti-MDA5 is presented. Although evidence is limited to small case series, cyclophosphamide (CYC) for refractory skin lesions, and CYC or mycophenolate mofetil plus a calcineurin inhibitor or rituximab (RTX) for RP-ILD appear efficacious. This is the largest North American case series of anti-MDA5-positive DM patients to date. There is a wide spectrum of clinical presentation of this entity. Survival is poor in those with RP-ILD; early aggressive immunosuppression and timely lung transplant were life-saving in our patients with RP-ILD.

Concurrent inflammatory myopathy and myasthenia gravis with or without thymic pathology: A case series and literature review.

OBJECTIVES: The association of myasthenia gravis (MG) and inflammatory myositis (IM) is rare and typically only one of the diseases is present. The management of the 2 diseases differs, therefore it is important to recognize the concomitant presentation. Here, we report a case series of 7 patients with co-existing MG and IM with review of the literature. METHOD: We identified 7 patients with concurrent MG and IM who were followed at the Neuromuscular Disease Program at a tertiary referral center in Vancouver, British Columbia from 2004 to 2017. RESULT: All 7 patients had ocular or bulbar involvement as manifestation of MG. Three patients had simultaneous onset of MG and IM, 2 of whom presented with myasthenia crisis and fulminant myositis. In the other 4 patients, MG was the initial presentation and IM occurred 3-11 years after MG. Among these 7 patients, 4 had underlying thymic pathology, including 2 with benign thymoma and 2 with stage IV thymoma; all 4 patients had antibodies to acetylcholine receptor (AChR). Of the 3 patients with no thymic pathology by imaging or histology, 2 had positive AChR antibody titer. For treatment, the thymoma was resected and chemotherapy was administered if appropriate. Additional immunosuppressive therapies including high-dose glucocorticoid, intravenous immunoglobulin (IVIG), methotrexate, mycophenolate, or cyclosporine were necessary to achieve remission. Two patients with no thymoma had refractory MG and IM, and both responded to rituximab. We also conducted a literature review on the clinical characteristics and management of this condition, and compared the previously reported cases to the patients in our series. CONCLUSION: This is one of the largest case series of MG-IM overlap with or without thymic pathology. In this cohort, the 2 disease entities can occur simultaneously, or one presents before the other. Most of the patients responded well to steroid, acetylcholinesterase inhibitor, and immunosuppressive agents. In very refractory cases, rituximab appeared to be effective, which has not been reported for the treatment of this condition before.

RNA-Seq Analysis of Gene Expression, Viral Pathogen, and B-Cell/T-Cell Receptor Signatures in Complex Chronic Disease.

Background: Chronic fatigue syndrome (CFS) remains poorly understood. Although infections are speculated to trigger the syndrome, a specific infectious agent and underlying pathophysiological mechanism remain elusive. In a previous study, we described similar clinical phenotypes in CFS patients and alternatively diagnosed chronic Lyme syndrome (ADCLS) patients­individuals diagnosed with Lyme disease by testing from private Lyme specialty laboratories but who test negative by reference 2-tiered serologic analysis. Methods: Here, we performed blinded RNA-seq analysis of whole blood collected from 25 adults diagnosed with CFS and 13 ADCLS patients, comparing these cases to 25 matched controls and 11 patients with well-controlled systemic lupus erythematosus (SLE). Samples were collected at patient enrollment and not during acute symptom flares. RNA-seq data were used to study host gene expression, B-cell/T-cell receptor profiles (BCR/TCR), and potential viral infections. Results: No differentially expressed genes (DEGs) were found to be significant when CFS or ADCLS cases were compared to controls. Forty-two DEGs were found when SLE cases were compared to controls, consistent with activation of interferon signaling pathways associated with SLE disease. BCR/TCR repertoire analysis did not show significant differences between CFS and controls or ADCLS and controls. Finally, viral sequences corresponding to anelloviruses, human pegivirus 1, herpesviruses, and papillomaviruses were detected in RNA-seq data, but proportions were similar (P = .73) across all genus-level taxonomic categories. Conclusions: Our observations do not support a theory of transcriptionally mediated immune cell dysregulation in CFS and ADCLS, at least outside of periods of acute symptom flares.

The rising prevalence and incidence of gout in British Columbia, Canada: Population-based trends from 2000 to 2012.

OBJECTIVES: Gout is increasingly recognized as the most common form of inflammatory arthritis worldwide; however, no Canadian data on the disease burden of gout are available. We estimated the prevalence, incidence, prescription patterns, and comorbidity burden of gout in an entire Canadian province [British Columbia (BC)] over the last decade. METHODS: We utilized PopulationData BC, a province-wide database, to estimate temporal trends in the prevalence and incidence of gout from 2000 to 2012, as well as according to age category. Annual estimates were age-sex-standardized using 2012 as the reference. We also examined annual trends in prescription patterns of common gout medications and assessed the comorbidity burden among gout patients in 2012. RESULTS: The 2012 prevalence of gout was 3.8% among the overall population, and the incidence rate was 2.9 per 1000 person-years. Both gout prevalence and incidence increased substantially over the study period. This burden additionally increased according to age category, affecting over 8% of those ages 60-69 years in 2012. Approximately 22% of gout patients received a prescription for urate-lowering therapy (ULT), which remained stable over the study period, while colchicine and oral glucocorticoid use both increased modestly. By 2012, 72%, 52%, and 18% of prevalent gout patients had been diagnosed with hypertension, hyperlipidemia, and diabetes, respectively. CONCLUSIONS: The burden of gout in BC, Canada, is substantial, and both the prevalence and incidence have increased over the past decade, while prescription of ULT remains low. These data support the need to improve gout prevention and care.

Experiences From a Combined Dermatology and Rheumatology Clinic: A Retrospective Review.

BACKGROUND: The Dermatology and Rheumatology Treatment Clinic is a novel multidisciplinary clinic where patients are concomitantly assessed by a rheumatologist and dermatologist. OBJECTIVES: To determine the number of patients seen in clinic, patient demographics, and most common diagnoses. METHOD: A retrospective review was performed over a 2-year period. Data collected included patient age, sex, dermatologic diagnosis, rheumatologic diagnosis, biopsies performed, and number of follow-up visits. RESULTS: A total of 320 patients were seen (78% female, 22% male). The most common rheumatologic diagnoses were systemic lupus erythematosus (18%), rheumatoid arthritis (15%), psoriatic arthritis (13%), and undifferentiated connective tissue disease (8%). The most common dermatologic diagnoses were dermatitis (17%), psoriasis (11%), cutaneous lupus (7%), various types of alopecia (6%), and infections (5%). CONCLUSIONS: Skin diagnoses were often unrelated to the underlying rheumatologic diagnosis. Rheumatologists and dermatologists can both benefit from being aware of the dermatologic conditions that rheumatologic patients are experiencing.

Efficacy, Tolerability, and Safety of Cannabinoid Treatments in the Rheumatic Diseases: A Systematic Review of Randomized Controlled Trials.

OBJECTIVE: To assess the efficacy, tolerability, and safety of cannabinoids (phyto- and syntheto-) in the management of rheumatic diseases. METHODS: Multiple databases, including Medline, Embase, and CENTRAL, were searched. Randomized controlled trials with outcomes of pain, sleep, quality of life, tolerability (dropouts due to adverse events), and safety (serious adverse events), with comparison of cannabinoids with any type of control, were included. Study methodology quality was evaluated with the Cochrane risk of bias tool. RESULTS: In 4 short-term studies comprising 203 patients (58 with rheumatoid arthritis, 71 with fibromyalgia, and 74 with osteoarthritis [OA]), cannabinoids had a statistically significant effect on pain in 2, sleep in 2, and improved quality of life in 1, with the OA study prematurely terminated due to futility. The risk of bias was high for all 3 completed studies. Dizziness, cognitive problems, and drowsiness, as well as nausea, were reported for almost half of the patients. No serious adverse events were reported for cannabinoids during the study duration. No studies of herbal cannabis were identified. CONCLUSION: Extremely small sample sizes, short study duration, heterogeneity of rheumatic conditions and products, and absence of studies of herbal cannabis allow for only limited conclusions for the effects of cannabinoids in rheumatic conditions. Pain relief and effect on sleep may have some potential therapeutic benefit, but with considerable mild to moderate adverse events. There is currently insufficient evidence to recommend cannabinoid treatments for management of rheumatic diseases pending further study.

Lyme Disease Diagnosed by Alternative Methods: A Phenotype Similar to That of Chronic Fatigue Syndrome.

BACKGROUND: A subset of patients reporting a diagnosis of Lyme disease can be described as having alternatively diagnosed chronic Lyme syndrome (ADCLS), in which diagnosis is based on laboratory results from a nonreference Lyme specialty laboratory using in-house criteria. Patients with ADCLS report symptoms similar to those reported by patients with chronic fatigue syndrome (CFS). METHODS: We performed a case-control study comparing patients with ADCLS and CFS to each other and to both healthy controls and controls with systemic lupus erythematosus (SLE). Subjects completed a history, physical exam, screening laboratory tests, 7 functional scales, reference serology for Lyme disease using Centers for Disease Control and Prevention criteria, reference serology for other tick-associated pathogens, and cytokine expression studies. RESULTS: The study enrolled 13 patients with ADCLS (12 of whom were diagnosed by 1 alternative US laboratory), 25 patients with CFS, 25 matched healthy controls, and 11 SLE controls. Baseline clinical data and functional scales indicate significant disability among ADCLS and CFS patients and many important differences between these groups and controls, but no significant differences between each other. No ADCLS patient was confirmed as having positive Lyme serology by reference laboratory testing, and there was no difference in distribution of positive serology for other tick-transmitted pathogens or cytokine expression across the groups. CONCLUSIONS: In British Columbia, a setting with low Lyme disease incidence, ADCLS patients have a similar phenotype to that of CFS patients. Disagreement between alternative and reference laboratory Lyme testing results in this setting is most likely explained by false-positive results from the alternative laboratory.

Cryofibrinogenemia After a Liver Transplant: First Reported Case Posttransplant and a Case-Based Review of the Nontransplant Literature.

Cryofibrinogenemia is a rare disorder in which plasma, not serum, forms a cryoprecipitate. Patients with cryofibrinogenemia may be asymptomatic, or they may have painful ulcers, purpura, livedo reticularis, Raynaud phenomenon, perniosis of the extremities, thrombosis, and arthralgia. Cryofibrinogenemia may be primary or secondary to an underlying disorder such as connective tissue disease, malignancy, infection, drugs, or thromboembolic disease. Here, we present a 41-year-old woman with a pancreatic neuroendocrine tumor who underwent a Whipple procedure in 2003 followed by 2 liver transplants for hepatic metastases. Three years posttransplant, we discovered a biopsy-proven metastatic lesion in her femur. Five years posttransplant, she developed acute, severe pain in both feet, and was found to have cryofibrinogenemia despite immunosuppression post-transplant. Testing for connective tissue diseases and hematologic malignancy were negative. She was treated with high-dose prednisone, which completely resolved her symptoms. We also conducted a review of the literature via a PubMed search to summarize the association of cryofibrinogenemia with malignancy and treating cryofibrinogenemia with corticosteroids. Our study is the first reported case of cryofibrinogenemia that developed secondary to a neuroendocrine tumor posttransplant. Our report suggests that cryofibrinogenemia may occur despite immunosuppression adequate to prevent graft rejection, and that high-dose corticosteroids are an effective treatment for posttransplant cryofibrinogenemia.

Trichodysplasia spinulosa: rare presentation of polyomavirus infection in immunocompromised patients.

BACKGROUND: Trichodysplasia spinulosa (TS) is a rare, striking, folliculocentric papular eruption seen exclusively in immunosuppressed patients. The eruption can be disfiguring, associated with leonine faces and alopecia. TS is caused by a polyomavirus, identified as trichodysplasia spinulosa polyomavirus (TSPyV). Few reports exist in the literature, and support for treatment options is sparse. METHOD AND RESULTS: We report a patient with TS with underlying lupus nephropathy and renal transplant-associated immunosuppression. Diagnosis was confirmed by biopsy and pathognomonic histologic findings in the context of her extensive, spiculated monomorphous papules. With a biopsy-confirmed diagnosis, oral valganciclovir was prescribed, and the patient showed marked skin texture improvement and hair regrowth. CONCLUSION: The continued reporting of cases of TS will improve clinical identification of this condition and provide better information regarding treatment and long-term consequences.

The issue of comparators in economic evaluations of biologic response modifiers in rheumatoid arthritis.

INTRODUCTION: Over the last decade, a number of biologic response modifiers (BRMs) have emerged and transformed rheumatoid arthritis (RA) management. Due to their relatively high costs, economic evaluations have attempted to determine their place in the RA treatment armamentarium. This article reviews three key areas where changes to the treatment paradigm challenges findings of existing economic evaluations. METHODS: We performed a literature search of economic evaluations examining BRMs approved for use in North America for RA. Only economic evaluations that examined relevant direct costs and health outcomes were included. Data were extracted and summarised, then stratified by patient population and comparators. Reported incremental cost-effectiveness ratios (ICERs) were compared across studies. RESULTS: It appears that tumour necrosis factor (TNF) alpha inhibitors are less cost effective compared to disease-modifying anti-rheumatic drugs (DMARDs) for first-line treatment. In addition, it appears that treatment with a TNF alpha inhibitor in patients who were refractory to previous DMARD therapies is more cost effective, compared to switching to another DMARD. Finally, after an inadequate response to a TNF alpha inhibitor, it appears that therapy with rituximab is more cost effective than treatment with another TNF alpha inhibitor or abatacept. DISCUSSION: It is important to acknowledge that cost effectiveness depends on which comparators are included in the analyses and the evidence for the comparators. The most typical comparator in the studies was traditional DMARDs, mainly methotrexate. However, as more BRMs come into the market and new clinical evidences emerge on the comparative effectiveness of BRMs, new economic evaluations will need to incorporate this information such that reimbursement decisions can be fully informed regarding relative value.

Application of linear discriminant analysis in performance evaluation of extractable nuclear antigen immunoassay systems in the screening and diagnosis of systemic autoimmune rheumatic diseases.

This study applied a linear discriminant analysis model to evaluate the performance of 2 types of commercially available extractable nuclear antigen (ENA) immunoassays for the screening and diagnosis of systemic autoimmune rheumatic diseases (SARDs) in a large tertiary hospital reference laboratory: (1) an enzyme-linked immunosorbent assay (ELISA) and (2) a multiplex bead-based immunoassay (MPBI). The results of the study showed both ENA immunoassays had comparable sensitivity for the detection of SARDs compared with the antinuclear antigen immunofluorescence (ANA-IF) method (ANA-IF: 85.6%, ENA-ELISA: 91.5%, ENA-MPBI: 83.1%, pairwise comparisons with ANA-IF: P > .05). However, both ENA immunoassays offered improved specificity compared with the ANA-IF (ANA-IF: 24.2%; ENA-ELISA: 39.8%; ENA-MPBI: 53.1%; pairwise comparison with ANA-IF: P < .001). The use of a more specific screening immunoassay with comparable sensitivity to ANA-IF is important in a tertiary hospital with high prevalence of non-SARD immune diseases. Diagnostic performance of the ENA/dsDNA components by the MPBI and ELISA methods did not differ significantly (area under the curve [AUC], 81.0% vs 83.0%, respectively, P > .05), but the key ENA/dsDNA variables contributing to the discriminating power of the assays for the diagnosis of specific SARDs were reagent/method dependent.

Beneficial effects of adalimumab on biomarkers reflecting structural damage in patients with ankylosing spondylitis.

OBJECTIVE: We analyzed the effects of adalimumab on biomarkers predictive of structural damage in inflammatory arthritis. METHODS: In a 24-week randomized controlled trial, patients with active ankylosing spondylitis (AS) received adalimumab 40 mg or placebo every other week. Efficacy measures included ASsessment in Ankylosing Spondylitis International Working Group response, Bath AS Disease Activity Index (BASDAI), Total Back Pain, Bath AS Functional Index, C-reactive protein (CRP), and patient's global assessment of disease activity. Urinary type II collagen C-telopeptides (CTX-II), serum type I collagen N-telopeptides (NTX), and serum metalloproteinase-3 (MMP-3) were assessed using ELISA for treatment-group differences at baseline, 12, and 24 weeks. We determined correlations between changes in biomarkers and AS efficacy outcomes. RESULTS: A total of 82 patients (38 adalimumab, 44 placebo) enrolled. At 12 and 24 weeks, significant reductions in urinary CTX-II and MMP-3, but not NTX concentrations, were observed for adalimumab versus placebo (p<0.001). Significant baseline correlations were noted between CRP and CTX-II (r=0.71), MMP-3 (r=0.45), and NTX (r=0.37) (p

Abatacept: a novel treatment for moderate-to-severe rheumatoid arthritis.

Rheumatoid arthritis is a chronic autoimmune disease that often leads to functional disability and reduced quality of life. The pathogenesis of synovial inflammation that is associated with this disease is thought to result from T-cell activation. To become fully activated, T cells require an antigen-specific signal through the T-cell receptor and a second signal through a costimulatory receptor. Abatacept is the first drug in a new class of disease-modifying antirheumatic drugs (DMARDs) known as selective costimulation modulators. Costimulation modulators block the second signal and decrease T-cell activation. Abatacept has been approved by the United States Food and Drug Administration for reducing signs and symptoms, inducing major clinical response, slowing the progression of structural damage, and improving physical function in adults with moderate-to-severe active rheumatoid arthritis who have had an inadequate response to at least one other DMARD, such as methotrexate or tumor necrosis factor (TNF)-alpha inhibitors. Randomized controlled trials have shown that abatacept improves both clinical outcomes and health-related quality of life in patients who have had an inadequate response to other DMARDs. Abatacept has been shown to be well tolerated. In clinical trials, however, abatacept treatment was associated with a higher rate of infections compared with placebo. This finding was compounded when abatacept was used with TNF-alpha inhibitors; thus, this combination should be avoided. Abatacept appears to be a useful treatment option for patients with rheumatoid arthritis who have previously failed other DMARDs. However, additional clinical trials evaluating its long-term effect on patient safety and disease outcomes are needed.

Infliximab treatment of rheumatoid arthritis and Crohn's disease.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, safety, and pharmacoeconomic impact of infliximab in the treatment of Crohn's disease (CD) and rheumatoid arthritis (RA). DATA SOURCES: MEDLINE and Pre-MEDLINE (1966-June 2002) and manufacturer prescribing literature were employed to find English-language articles on infliximab. Additional studies and abstracts were identified from the bibliographies of reviewed literature and conference proceedings. STUDY SELECTION/DATA EXTRACTION: All articles identified from data sources were evaluated, and all information deemed relevant was included in this review. Information regarding basic pharmacology was collected from studies in animals. Pharmacokinetic data were collected from human trials. Safety data were extracted from clinical trials and postmarketing surveillance. Priority was given to randomized, double-blind, placebo-controlled studies for the assessment of efficacy. All available economic evaluations were included. DATA SYNTHESIS: Infliximab is a new monoclonal antibody that appears to work by a unique mechanism: inhibiting the action of tumor necrosis factor-alpha (TNF-alpha). Infliximab is administered by intravenous infusion. In clinical trials in CD, infliximab significantly decreased the CD activity index compared with placebo in treatment-resistant disease and significantly reduced the number of draining fistulas in fistulizing disease. In RA, when infliximab was added to methotrexate (MTX), it resulted in a significant improvement in most disease outcome measures when compared with MTX plus placebo. Few major adverse effects were reported in the clinical trials; however, serious adverse events, including malignancy and demyelination, have been reported in postmarketing surveillance. Also, increased susceptibility to infections (including tuberculosis) has been reported. CONCLUSIONS: Infliximab is an effective new agent for the treatment of CD and RA. Its apparent unique mechanism of action makes infliximab an important addition to therapy. Caution should be exercised when considering infliximab for individuals who have chronic or recurrent infections, mild congestive heart failure (New York Heart Association [NYHA] class I/II), nervous system disorders, or live or have lived in an area endemic for histoplasmosis. Infliximab is contraindicated for patients with a clinically important, active infection, moderate to severe congestive heart failure (NYHA class III/IV), or an allergy to mouse proteins or any of the ingredients in infliximab. Further long-term efficacy, safety, and economic data on infliximab are required. Also, for the treatment of RA, the burden of administering infliximab (as a 2-hour supervised infusion) has to be considered when choosing among anti-TNF-alpha medication (as the other 2 approved agents, etanercept and adalimumab, can be self-administered by subcutaneous injection).