Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

HIV-related non-Hodgkin’s lymphoma in Calgary

OBJECTIVE: To determine the incidence of human immunodeficiency virus (HIV) associated non-Hodgkin’s lymphoma (NHL) in a cohort of patients from a distinct geographic region (southern Alberta). The type and location of NHL as well as how it affected the survival of these patients was examined

HIV-Related Non-Hodgkin’s Lymphoma in Calgary

OBJECTIVE: To determine the incidence of human immunodeficiency virus (HIV) associated non-Hodgkin’s lymphoma (NHL) in a cohort of patients from a distinct geographic region (southern Alberta). The type and location of NHL as well as how it affected the survival of these patients was examined.PATIENTS AND METHODS: The Southern Alberta HIV Clinic in Calgary serves all of southern Alberta, which has an estimated population of one million. The clinic has provided primary care for 1086 patients from January 1983 to August 1995. Data were obtained by reviewing the clinic’s database and patients’ charts.RESULTS: Over a 12-year period, 39 cases of NHL were diagnosed in a group of 1086 HIV-infected patients. Presentation of NHL was at an extranodal site in all but four cases, with the most common sites being the bowel and central nervous system. The mean CD4 count on presentation with NHL was 143.4±37.4×106/L (range 1 to 1219×106/L). Mean survival was 1.25±0.25 years with a range from 0 (diagnosed on autopsy) to 6.45 years. Patients with a CD4 count of less than 200×106/L and/or diagnosed with an AIDS-defining illness before development of NHL had significantly reduced survival (0.85 years versus 2.48 years, Pud_less_than0.02 and 0.57 years versus 2.09 years, Pud_less_than0.001, respectively). Patients who presented with NHL involving either nodes alone or central nervous system had significantly decreased survival (0.28 years and 0.29 years, respectively, Pud_less_than0.05). Patients with NHL involving the gastrointestinal tract had a longer mean survival than those with NHL elsewhere (Pud_less_than0.05). All but seven cases received therapy for NHL including chemotherapy, radiotherapy, surgery or combined therapy. Fifteen patients (47% of treated) achieved a complete response that led to improved survival (Pud_less_than0.01). Patients tolerated surgery, chemotherapy and radiotherapy well and no deaths were due to NHL therapy.CONCLUSIONS: These data suggest that development of NHL in HIV is associated with reduced survival, and that survival is predominantly determined by CD4 count and site of involvement at the time of diagnosis of NHL.Peer Reviewe