Search

Background: The efficacy-effectiveness gap between randomized trial and real-world evidence regarding the clinical benefit of ipilimumab for metastatic melanoma (MM) has been well characterized by previous literature, consistent with initial concerns raised by health technology assessment agencies (HTAs). As these differences can significantly impact cost-effectiveness, it is critical to assess the real-world cost-effectiveness of second-line ipilimumab versus non-ipilimumab treatments for MM. Methods: This was a population-based retrospective cohort study of patients who received second-line non-ipilimumab therapies between 2008 and 2012 versus ipilimumab treatment between 2012 and 2015 (after public reimbursement) for MM in Ontario. Using a 5-year time horizon, censor-adjusted and discounted (1.5%) costs (from the public payer's perspective in Canadian dollars) and effectiveness were used to calculate incremental cost-effectiveness ratios (ICERs) in life-years gained (LYGs) and quality-adjusted life years (QALYs), with bootstrapping to capture uncertainty. Varying the discount rate and reducing the price of ipilimumab were done as sensitivity analyses. Results: In total, 329 MM were identified (Treated: 189; Controls: 140). Ipilimumab was associated with an incremental effectiveness of 0.59 LYG, incremental cost of $91,233, and ICER of $153,778/LYG. ICERs were not sensitive to discounting rate. Adjusting for quality of life using utility weights resulted in an ICER of $225,885/QALY, confirming the original HTA estimate prior to public reimbursement. Reducing the price of ipilimumab by 100% resulted in an ICER of $111,728/QALY. Conclusion: Despite its clinical benefit, ipilimumab as second-line monotherapy for MM patients is not cost-effective in the real world as projected by HTA under conventional willingness-to-pay thresholds. [ABSTRACT FROM AUTHOR]

Objective: To investigate the incidence of and factors associated with SARS–CoV‐2 testing and infection in immune‐mediated inflammatory disease (IMID) patients versus matched non‐IMID comparators from the general population. Methods: We conducted a population‐based, matched cohort study among adult residents from Ontario, Canada, from January 2020 to December 2020. We created cohorts for the following IMIDs: rheumatoid arthritis (RA), psoriasis, psoriatic arthritis, ankylosing spondylitis, systemic autoimmune rheumatic diseases, multiple sclerosis (MS), iritis, inflammatory bowel disease (IBD), polymyalgia rheumatica, and vasculitis. Each patient was matched with 5 patients without IMIDs based on sociodemographic factors. We estimated the incidence of SARS–CoV‐2 testing and infection in IMID patients and non‐IMID patients. Multivariable logistic regressions assessed odds of SARS–CoV‐2 infection. Results: We studied 493,499 patients with IMIDs and 2,466,946 patients without IMIDs. Patients with IMIDs were more likely to have at least 1 SARS–CoV‐2 test versus patients without IMIDs (27.4% versus 22.7%), but the proportion testing positive for SARS–CoV‐2 was identical (0.9% in both groups). Overall, IMID patients had 20% higher odds of being tested for SARS–CoV‐2 (odds ratio 1.20 [95% confidence interval 1.19–1.21]). The odds of SARS–CoV‐2 infection varied across IMID groups but was not significantly elevated for most IMID groups compared with non‐IMID comparators. The odds of SARS–CoV‐2 infection was lower in IBD and MS and marginally higher in RA and iritis. Conclusion: Patients across all IMIDs were more likely to be tested for SARS–CoV‐2 versus those without IMIDs. The risk of SARS–CoV‐2 infection varied across disease subgroups. [ABSTRACT FROM AUTHOR]

Objective: The study objective was to assess adherence to system‐level performance measures measuring retention in rheumatology care and disease modifying anti‐rheumatic drug (DMARD) treatment in rheumatoid arthritis (RA). Methods: We used a validated health administrative data case definition to identify individuals with RA in Ontario, Canada, between 2002 and 2014 who had at least 5 years of potential follow‐up prior to 2019. During the first 5 years following diagnosis, we assessed whether patients were seen by a rheumatologist yearly and the proportion dispensed a DMARD yearly (in those aged ≥66 for whom medication data were available). Multivariable logistic regression analyses were used to estimate the odds of remaining under rheumatologist care. Results: The cohort included 50,883 patients with RA (26.1% aged 66 years and older). Over half (57.7%) saw a rheumatologist yearly in all 5 years of follow‐up. Sharp declines in the percentage of patients with an annual visit were observed in each subsequent year after diagnosis, although a linear trend to improved retention in rheumatology care was seen over the study period (P < 0.0001). For individuals aged 66 years or older (n = 13,293), 82.1% under rheumatologist care during all 5 years after diagnosis were dispensed a DMARD annually compared with 31.0% of those not retained under rheumatology care. Older age, male sex, lower socioeconomic status, higher comorbidity score, and having an older rheumatologist decreased the odds of remaining under rheumatology care. Conclusion: System‐level improvement initiatives should focus on maintaining ongoing access to rheumatology specialty care. Further investigation into causes of loss to rheumatology follow‐up is needed. [ABSTRACT FROM AUTHOR]

Second‐line ipilimumab has been publicly funded in Ontario for metastatic melanoma (MM) since September 2012. We examined real‐world toxicity of second‐line ipilimumab compared to standard second‐line treatments prior to funding. MM patients who received systemic treatment from April 2005 to March 2015 were included. Patients receiving second‐line ipilimumab after September 2012 were considered as cases, and those who received second‐line treatment prior to the funding date were included as historical controls. Outcomes assessed include treatment‐related mortality, any‐cause hospital visits, ipilimumab‐related hospital visits and specialist visits (eg, endocrinologists, ophthalmologists, gastroenterologists, rheumatologists and respirologists), which were captured from up to 30 and/or 90 days after end of second‐line treatment. Inverse probability of treatment weighting was used to adjust for baseline differences between groups. Odds ratios (ORs) from logistic regressions and rate ratios (RRs) from rate regressions were used to assess differences between groups. We identified 329 MM patients who received second‐line treatments (ipilimumab: 189; controls: 140). Ipilimumab was associated greater any‐cause (60.1% vs 45.7%; OR = 1.81; P value =.019) and ipilimumab‐related (47.2% vs 31.9%; OR = 1.91; P value =.011) hospital visits. Adjusting for different follow‐up days, ipilimumab was associated with higher rates of all‐cause (RR = 1.56 [95%CI: 1.12‐2.16]), and ipilimumab‐related (RR = 2.18 [95% CI: 1.45‐3.27]) hospital visits. Patients receiving ipilimumab were more likely to visit specialist involved in immunotherapy toxicity management (23.5% vs 13.7%; P value =.04). Compared to historical second‐line treatments, second‐line ipilimumab was associated with more health service utilization (specifically hospital visits and specialist visits), suggestive of potentially increased toxicity in the real world. What's new? Ipilimumab improves overall survival in metastatic melanoma. But how toxic is it in real‐world use? In this population‐based, comparative study, the authors found that patients receiving second‐line ipilimumab required more hospital (all‐cause and drug‐related) and specialist visits compared to historical controls. These findings suggest that ipilimumab is associated with greater toxicity and resource utilization than conventional treatments. Given that patients in actual clinical practice may have additional comorbidities compared to patients selected for clinical trials, it is important to further examine toxicity in a real‐world setting in order to better understand the risks. [ABSTRACT FROM AUTHOR]

Summary: Preclinical data suggests anti‐lymphoma potential for statins, metformin and cyclooxygenase‐2 (COX‐2) inhibitors. We performed a retrospective population‐based study of all adults aged ≥66 years diagnosed with diffuse large B‐cell lymphoma (DLBCL) or transformed lymphoma treated with a rituximab containing regimen, between 2005 and 2015 in Ontario, Canada. Using administrative databases, we assessed the impact of medication exposures, prior to chemo‐immunotherapy, on lymphoma survival. Cox regression analyses, controlling for sociodemographic factors and comorbidities, examined the relationship between medication exposure and survival. In total, 4913 patients were treated with curative intent (median age 75 years, 51% male) and 52·2% died at a median of 1 year from treatment initiation (67% due to DLBCL). In the year prior to commencing treatment, 45·7% received statins, 16·3% metformin, and 25·0% a COX‐2 inhibitor. Adjusting for confounders, exposure to statin and COX‐2 inhibitors prior to chemo‐immunotherapy independently conferred a survival advantage: statin exposure for 30 days (hazard ratio [HR] 0·97, 95% confidence interval [CI] 0·96–0·98), 180 days (HR 0·84, 95% CI 0·80–0·89) and 365 days (HR 0·71, 95% CI 0·63–0·79) and COX‐2 inhibitor exposure for 30 days (HR 0·95, 95% CI 0·95–0·98), 180 days (HR 0·76, 95% CI 0·66–0·86) and 365 days (HR 0·57, 95% CI 0·43–0·74). Metformin had no significant impact. This population‐based study found a dose‐related survival benefit of exposure to statins and COX‐2 inhibitors prior to chemo‐immunotherapy for newly diagnosed DLBCL. [ABSTRACT FROM AUTHOR]

Vitamin B6 is important in fetal development, but little is known of the vitamin B6 status of pregnant women and newborns in North America and potential modifying factors. This prospective study determined maternal and cord plasma concentrations of pyridoxal 5′ phosphate (PLP; an indicator of vitamin B6 status) in a convenience sample of 368 Canadian pregnant women and their newborns. The association of maternal intake of vitamin B6 and fetal genetic variants with cord plasma PLP and homocysteine concentrations was also examined. Dietary and supplemental intakes of vitamin B6 were assessed in early and mid to late pregnancy. PLP concentrations were measured in maternal plasma in early pregnancy and at delivery, and in cord plasma. Six fetal variants of the MTHFR and CβS genes were assessed for their association with cord plasma PLP and homocysteine concentrations. Geometric mean (95% CI) PLP concentrations were 107 (98, 116) nmol/L in early pregnancy and 58 (53, 62) nmol/L at delivery, respectively, and 296 (275, 319) nmol/L in cord blood ( p < .0001). During early pregnancy and at delivery, 3.6% and 5.5% of women had plasma PLP concentrations <20 nmol/L, respectively. Ninety eight percent of the women with supplemental B6 intake of at least the recommended dietary allowance had PLP concentrations >20 nmol/L. Fetal genetic variants were not associated with cord PLP and homocysteine concentrations. Vitamin B6 deficiency is uncommon in a cohort of Canadian pregnant women due largely to prevalent vitamin B6 supplement use. [ABSTRACT FROM AUTHOR]

Objective Therapeutic intraarticular injections are used in the management of hip osteoarthritis (OA). Some studies suggest that their use increases the risk of infection and subsequent revision surgery after primary total hip arthroplasty (THA), while others do not. We undertook this study to clarify the relationship between prior intraarticular injection and the risk of complication in a subsequent primary THA. Methods In a cohort of patients with hip OA who underwent a primary elective THA between 2002 and 2009, we identified those who received ≥1 intraarticular injection performed by a radiologist in the 5 years preceding their THA. Multivariable Cox proportional hazards models were used to determine the relationship between receipt of a presurgical injection (no injection, 1-5 years prior to THA, or <1 year prior to THA) and the occurrence of postsurgical joint infection and revision THA in the following 2 years, while controlling for confounders. Results Of 37,881 eligible THA recipients, 2,468 (6.5%) received an intraarticular injection performed by a radiologist within 5 years of their THA (1,691 at <1 year, 777 at 1-5 years). Controlling for age, sex, comorbidity, frailty, income, and provider volume, those who had an injection in the year preceding surgery were at increased risk of infection (adjusted hazard ratio [HR] 1.37, P = 0.03) and revision THA (adjusted HR 1.53, P = 0.03) within 2 years of the primary THA, relative to patients who did not. The association between prior injection and revision arthroplasty was attenuated and became nonsignificant (adjusted HR 1.41, P = 0.13) after occurrence of postoperative infection was controlled for in the regression model. No effect was found for injection 1-5 years prior to surgery. Conclusion Intraarticular injection in the year preceding THA independently predicted increased risk of infection leading to early revision surgery. Further studies are warranted to elucidate explanations for these findings. [ABSTRACT FROM AUTHOR]

Objective To determine the relationship between surgeon experience with, and complications following, total joint arthroplasty (TJA) in patients with rheumatoid arthritis (RA). Methods Using administrative data, we assembled a cohort of patients with RA who had undergone at least 1 elective primary hip or knee replacement procedure between 2002 and 2009. Cox proportional hazards, censored on death and accounting for clustering of patients within surgeons, were used to determine the relationship between overall and 'RA-specific' surgeon TJA volume and the occurrence of a composite 'complication' outcome (revision, infection, dislocation, or periprosthetic fracture within 2 years of the initial TJA), controlling for potential confounders (patient age, sex, comorbidity, and disease severity). Results We identified 4,762 patients with RA who were eligible for TJAs (1,515 total hip arthroplasties and 3,247 total knee arthroplasties). Among these patients, 152 (3.2%) experienced a surgical complication within 2 years of the procedure. After controlling for patient and hospital factors, greater surgeon TJA volume in patients with RA (RA TJA), but not overall TJA volume (all TJA), was associated with a reduced risk of complications (for surgeon RA TJA volume per 10 cases, adjusted hazard ratio [HR] 0.81, 95% confidence interval [95% CI] 0.71-0.93, P = 0.002; for surgeon all TJA volume, adjusted HR 0.98, 95% CI 0.97-1.00, P = 0.09). Conclusion In a cohort of patients with RA who underwent hip or knee TJA, increased surgeon experience performing TJA in patients with RA, irrespective of their overall TJA experience and hospital factors, was associated with a decreased risk of surgical complications. These findings have potential implications for surgeon training and the referral practices of rheumatologists. [ABSTRACT FROM AUTHOR]

Objective Most of the evidence regarding complications following total hip arthroplasty (THA) and total knee arthroplasty (TKA) are based on patients with osteoarthritis (OA); less is known about outcomes in rheumatoid arthritis (RA). Using a validated algorithm for identifying patients with RA, we undertook this study to compare the rates of complications among THA and TKA recipients between those with RA and those without RA. Methods In patients who underwent a first primary elective THA or TKA between 2002 and 2009, those with RA were identified using a validated algorithm: a hospitalization with a diagnosis code for RA or 3 physician billing claims with a diagnosis code for RA, with at least 1 claim by a specialist (rheumatologist, orthopedic surgeon, or internist) in a 2-year period. Recipients with diagnostic codes suggesting an inflammatory arthritis, but not meeting RA criteria, were classified as having inflammatory arthritis. All remaining patients were deemed to have OA. Cox proportional hazards models, censored on death, were used to determine the relationship between the type of arthritis and the occurrence of specific complications, adjusting for potential confounders (age, sex, comorbidity, and provider volume). Results We identified 43,997 eligible THA recipients (3% with RA) and 71,793 eligible TKA recipients (4% with RA). Total joint arthroplasty recipients with RA had higher age and sex-standardized rates of dislocation following THA (2.45%, compared with 1.21% for recipients with OA) and higher age and sex-standardized rates of infection following TKA (1.26%, compared with 0.84% for recipients with OA). Controlling for potential confounders, recipients with RA remained at increased risk of dislocation within 2 years of THA (adjusted hazard ratio [HR] 1.91, P = 0.001) and remained at increased risk of infection within 2 years of TKA (adjusted HR 1.47, P = 0.03) relative to recipients with OA. Conclusion Patients with RA are at higher risk of dislocation following THA and are at higher risk of infection following TKA relative to those with OA. Further research is warranted to elucidate explanations for these findings, including the roles of medication profile, implant choice, postoperative antibiotic protocol, and method of rehabilitation following joint replacement. [ABSTRACT FROM AUTHOR]

Objective To evaluate patient predictors of good outcome following total joint arthroplasty (TJA). Methods A population cohort with hip/knee arthritis (osteoarthritis [OA] or inflammatory arthritis) ages ≥55 years was recruited between 1996 and 1998 (baseline) and assessed annually for demographics, troublesome joints, health status, and overall hip/knee arthritis severity using the Western Ontario and McMaster Universities OA Index (WOMAC). Survey data were linked with administrative databases to identify primary TJAs. Good outcome was defined as an improvement in WOMAC summary score greater than or equal to the minimal important difference (MID; 0.5 SD of the mean change). Logistic regression and Akaike's information criterion were used to determine the optimal number of predictors and the best model of that size. Log Poisson regression was used to determine the relative risk (RR) for a good outcome. Results Primary TJA was performed in 202 patients (mean age 71.0 years; 79.7% female; 82.7% with >1 troublesome hip/knee; 65.8% knee replacements). Mean improvement in WOMAC summary score was 10.2 points (SD 18.05; MID 9 points). Of these patients, 53.5% experienced a good outcome. Four predictors were optimal. The best 4-variable model included pre-TJA WOMAC, comorbidity, number of troublesome hips/knees, and arthritis type (C statistic 0.80). The probability of a good outcome was greater with worse (higher) pre-TJA WOMAC summary scores (adjusted RR 1.32 per 10-point increase; P < 0.0001), fewer troublesome hips/knees (adjusted RR 0.82 per joint; P = 0.002), OA (adjusted RR for rheumatoid arthritis versus OA 0.33; P = 0.009), and fewer comorbidities (adjusted RR per condition 0.88; P = 0.01). Conclusion In an OA cohort with a high prevalence of multiple troublesome joints and comorbidity, only half achieved a good TJA outcome, defined as improved pain and disability. A more comprehensive assessment of the benefits and risks of TJA is warranted. [ABSTRACT FROM AUTHOR]

How models of health care financing and delivery affect patterns of procedure volumes, outcomes, and volume-outcome associations is not known. We compared volume-outcome studies done in Canada, which provides residents with universal, single-payer health care, with those done in the United States, to determine whether there was a difference in the likelihood of finding statistically significant volume-outcome associations. We analyzed 142 articles, most (90.1%) of which were from the United States. The articles described a total of 291 separate analyses. After adjusting for the clustering of multiple analyses in the same study, the likelihood of finding a statistically significant volume-outcome association was substantially lower in Canadian studies as compared with those from the United States (odds ratio 0.24, 95% confidence interval 0.08 to 0.74, p = 0.01). This result persisted after adjustment for the procedure/condition studied, and the number of study subjects. Canadian volume-outcome analyses are less likely to identify statistically significant volume-outcome associations than US studies, possibly because of the smaller size of some Canadian studies. It is also possible that different models of health care financing and delivery affect patterns of procedure volumes and volume-outcome associations. By promoting competition between hospitals and providers, market-based models may exacerbate existing variations in the quality of hospital care. [ABSTRACT FROM AUTHOR]

The hallmark of chronic myelogenous leukaemia (CML) is the presence of the Philadelphia chromosome and its resultant fusion message, BCR-ABL, and fusion protein, p210. Patients with CML in blast crisis, or with Philadelphia positive acute lymphoblastic leukaemia (ALL), can have a smaller BCR-ABL fusion transcript possessing only the first exon of BCR fused to ABL. This smaller transcript encodes a 190 kD protein which is more strongly transforming than the p210 protein derived from the larger CML-associated transcript. We performed RT-PCR on samples from CML patients in chronic phase to determine the frequency and mechanism of p190 and p210 co-expression and to see if this correlated with clinical indices. We examined the peripheral blood or marrow of 67 patients with CML and found that 35 of them expressed both transcripts whereas the remainder expressed the p210-encoding transcript exclusively. Additional PCR products of an intermediate size were also frequently detected and have been isolated and sequenced. Data from two of these products indicate that they are the result of alternative splicing and include variable combinations of BCR exons. We believe that the expression of the p190-encoding transcript in the chronic phase of CML is also due to alternative splicing. A comparison of patients co-expressing the p190- and p210-encoding transcripts with those patients who expressed only the p210-encoding transcript detected significantly higher white blood cell (WBC) counts and blast cell counts at time of testing as well as significantly higher white blood cell counts at diagnosis. [ABSTRACT FROM AUTHOR]

Objective: To examine prospectively the predictors of time to total joint arthroplasty (TJA)., Methods: This was a prospective cohort study with a median followup time of 6.1 years. We included participants from an existing population-based cohort of 2,128 individuals, ages 55 years and older with disabling hip and/or knee arthritis and no prior TJA, from 2 regions of Ontario, Canada, 1 urban with low TJA rates and 1 rural with high rates. The main outcome measure was the occurrence of a TJA based on procedure codes in the hospital discharge abstract database., Results: At baseline, the mean age of the patients was 71.5 years, 67.9% had a high school education or higher, 73.4% were women, the mean arthritis severity (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) score was 41.1 (maximum possible score 100), and 20.0% were willing to consider TJA. Greater probability of undergoing TJA was associated with higher (worse) baseline WOMAC scores (hazard ratio [HR] 1.22 per 10-unit increase, P < 0.001), age (compared with age or=82 years; P < 0.05 for all), better health (HR 1.14 per 10-unit increase in Short Form 36 general health survey score, P < 0.001), and willingness to consider TJA (HR 4.92, P < 0.001). When willingness was excluded from the model, education level, but not sex or income, became a significant predictor of TJA receipt., Conclusion: Willingness to consider TJA was the strongest predictor of the time to first TJA. Given that previous research indicates that willingness is largely explained by perceptions of the indications for and risks associated with TJA and not disease severity, this finding supports the need for population education about arthritis treatments, including TJA.