Kam Shojania

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 Crohns 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-α (TNF-α). 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-α medication (as the other 2 approved agents, etanercept and adalimumab, can be self-administered by subcutaneous injection).

Canadian Recommendations for Use of Methotrexate in Patients with Rheumatoid Arthritis

Objective. To develop recommendations for the use of methotrexate (MTX) in patients with rheumatoid arthritis. Methods. Canadian rheumatologists who participated in the international 3e Initiative in Rheumatology (evidence, expertise, exchange) in 2007–2008 formulated 5 unique Canadian questions. A bibliographic team systematically reviewed the relevant literature on these 5 topics. An expert committee consisting of 26 rheumatologists from across Canada was convened, and a set of recommendations was proposed based on the results of systematic reviews combined with expert opinions using a nominal group consensus process. Results. The 5 questions addressed drug interactions, predictors of response, strategies to reduce non-serious side effects, variables to assess clinical response, and incorporating patient preference into decision-making. The systematic review retrieved 93 pertinent articles; this evidence was presented to the expert committee during the interactive workshop. After extensive discussion and voting, a total of 9 recommendations were formulated: 2 on drug interactions, 1 on predictors of response, 2 on strategies to reduce non-serious side effects, 3 on variables to assess clinical response, and 1 on incorporating patient preferences into decision-making. The level of evidence and the strength of recommendations are reported. Agreement among panelists ranged from 85% to 100%. Conclusion. Nine recommendations pertaining to the use of MTX in daily practice were developed using an evidence-based approach followed by expert/physician consensus with high level of agreement.

Do spouses know how much fatigue, pain, and physical limitation their partners with rheumatoid arthritis experience? Implications for social support†

To determine whether perceptions of clinical manifestations (fatigue, pain, and physical limitation) of rheumatoid arthritis (RA) differ between spouses and their partners with RA, and to determine whether the differences are associated with the perception of beneficial and problematic spousal social support.

Subsequent entry biologics/biosimilars: a viewpoint from Canada.

We have reviewed the issues surrounding the advent of biosimilars in the rheumatoid arthritis biologic field. Our proposals emphasize the need to focus primarily on patient safety and to assess the outcomes of therapy both in the short and longer term.

Septic arthritis in patients with pre-existing inflammatory arthritis

The case: A 56-year-old woman presents to her family physician with a 7-day history of tenderness, swelling and redness of 2 metacarpophalangeal joints and 1 proximal interphalangeal joint in her right hand. She also reports pain and redness of her right knee that makes it difficult to walk. On

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.

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)‐α 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‐α 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.

Rheumatologists lack confidence in their knowledge of cannabinoids pertaining to the management of rheumatic complaints

BackgroundArthritis pain is reported as one of the most common reasons for persons using medical herbal cannabis in North America. “Severe arthritis” is the condition justifying legal use of cannabis in over half of all authorizations in Canada, where cannabis remains a controlled substance. As champions for the care of persons with arthritis, rheumatologists must be knowledgeable of treatment modalities both traditional and non-traditional, used by their patients. As study of cannabinoid molecules in medicine is recent, we have examined the confidence in the knowledge of cannabinoids expressed by Canadian rheumatologists.MethodsThe confidence of rheumatologists in their knowledge of cannabinoid molecules and mechanisms relevant to rheumatology, and their ability to advise patients about cannabinoid treatments was recorded by an online questionnaire circulated via email to the entire Canadian Rheumatology Association membership.ResultsOver three quarters of the 128 respondents lacked confidence in their knowledge of cannabinoid molecules. While 45% of respondents believed there was no current role for cannabinoids in rheumatology patient care, only 25% supported any use of herbal cannabis. With 70% never having previously prescribed or recommended any cannabinoid treatment, uncertainty regarding good prescribing practices was prevalent. Concerns about risks of cannabis use were in line with the current literature.ConclusionsRheumatologists lacked confidence in their knowledge of cannabinoid molecules in general and in their competence to prescribe any cannabinoid for rheumatic complaints. In line with this uncertainty, there is reticence to prescribe cannabinoid preparations for rheumatology patients. Guidance is required to inform rheumatologists on the evidence regarding cannabinoids.

Group visits for rheumatoid arthritis patients: a pilot study

This pilot study explored the feasibility of a group visit model for patients with rheumatoid arthritis (RA) and for medical staff at a private practice. RA patients were invited to attend six 3.5-h-long group visit sessions held once per month at a wellness center. Each included group discussion, individual patient examinations, interactive question, and answer periods, and topic-specific presentations from various health professionals. Nineteen of the 24 RA patients invited to the group visits agreed to attend, and 13 to 15 were present at any given session. Participants expressed a high level of satisfaction in evaluation forms completed at the end of the last session. Group visits allowed the rheumatologist to spend more time providing advice for various health issues and eliminated the need to repeat advice about common issues. This group visit model is feasible for motivated RA patients who can meet the time commitment involved.

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.