Cost-Effectiveness of Colchicine Prophylaxis for Gout Flares When Commencing Allopurinol.

OBJECTIVE: Colchicine prophylaxis to prevent gout flares when commencing urate-lowering therapy is recommended by international rheumatology society guidelines. Whether this is a cost-effective intervention is currently unknown. Our objective was to perform a cost-effectiveness analysis using both a US cost input model and an Australian cost input model. METHODS: This cost-effectiveness analysis was completed from the point of view of the third-party payer. We used a 2-arm decision tree with 1 arm commencing allopurinol with no colchicine prophylaxis and the other with colchicine prophylaxis. Model inputs were drawn from published literature where available. We completed a univariate and probabilistic sensitivity analysis to confirm the robust nature of the modeling. The time frame for the model was 6 months. RESULTS: The colchicine prophylaxis arm resulted in a cost of $1,276 and 0.49 quality-adjusted life-years (QALYs), while in the placebo arm the cost was $516 and 0.47 QALYs, with an incremental cost-effectiveness ratio of $34,004 per QALY gained. In Australia, where cost of colchicine was much lower, the colchicine arm dominated the placebo ($208 [Australian] in the colchicine arm versus $415 [Australian] in the placebo). Univariate and probability sensitivity analysis demonstrated that results were robust to changes in input parameters. In the probabilistic sensitivity analysis, the probability of colchicine prophylaxis being the most cost-effective option was 93% in the US and 100% in the Australian setting. CONCLUSION: Colchicine prophylaxis to prevent gout flares while commencing allopurinol in gout is very cost-effective.

Prescription of Colchicine with Other Dangerous Concomitant Medications: A Nation-Wide Survey Using the Japanese Claims Database.

The anti-inflammatory agent colchicine may cause toxic effects such as rhabdomyolysis, pancytopenia, and acute respiratory distress syndrome in cases of overdose and when patients have renal or liver impairment. As colchicine is a substrate for CYP3A4 and P-glycoprotein (P-gp), drug-drug interactions are important factors that cause fatal colchicine-related side effects. Thus, we conducted a nation-wide survey to determine the status of inappropriate colchicine prescriptions in Japan. Patients prescribed the regular use of colchicine from April 2014 to March 2017 were identified using the Japanese large health insurance claims database. As the primary endpoint, we evaluated the concomitant prescription proportions of strong CYP3A4 and/or P-gp inhibitors classified as "contraindications for co-administration" with colchicine in patients with renal or liver impairment. We defined these cases as "inappropriate colchicine prescriptions." Additionally, factors affecting inappropriate colchicine prescriptions were analyzed. Among the 3302 enrolled patients, 43 (1.30%) were inappropriately prescribed colchicine. Of these 43 patients, 11 had baseline renal and/or liver impairment. By multiple regression analysis, the primary diseases "gout" and "Behçet's disease" were extracted as independent factors for inappropriate colchicine prescriptions with odds ratios of 0.40 (95% confidence interval: 0.19-0.84) and 4.93 (95% confidence interval: 2.12-11.5), respectively. We found that approximately 1% of patients had important colchicine interactions. Particularly, Behçet's disease was a risk factor for inappropriate prescriptions, with approximately 25% of patients showing renal and/or liver impairment (classified as "contraindications for co-administration"). These findings may be useful for medical professionals who prescribe colchicine therapy.

In older adults, new use of allopurinol or febuxostat was linked to hypersensitivity reactions versus colchicine.

SOURCE CITATION: Singh JA, Cleveland JD. Hypersensitivity reactions with allopurinol and febuxostat: a study using the Medicare claims data. Ann Rheum Dis. 2020;79:529-35. 32024648.

Hypersensitivity reactions with allopurinol and febuxostat: a study using the Medicare claims data.

OBJECTIVE: To assess the risk of hypersensitivity reactions (HSRs) with allopurinol and febuxostat in a population-based study. METHODS: We used the 5% Medicare beneficiary sample (≥65 years) from 2006 to 2012 to identify people with a newly filled prescription for allopurinol, febuxostat or colchicine. We used multivariable-adjusted Cox regression analyses to compare the hazard ratio (HR) of incident HSRs with allopurinol or febuxostat use versus colchicine use; separate analyses were done in people exposed to allopurinol. Propensity-matched analyses (5:1) compared hazards with allopurinol versus febuxostat. RESULTS: Crude incidence rates of HSRs were as follows: allopurinol, 23.7; febuxostat, 30.7; and colchicine, 25.6 per 1000 person-years. Compared with colchicine, allopurinol, febuxostat and febuxostat+colchicine were associated with significantly higher HRs of HSRs, 1.32 (95% CI: 1.10 to 1.60) and 1.54 (95% CI: 1.12 to 2.12) and 2.17 (95% CI: 1.18 to 3.99), respectively. In propensity-matched analyses, febuxostat did not significantly differ from allopurinol; HR for HSRs was 1.25 (95% CI: 0.93 to 1.67). Compared with allopurinol start dose <200 mg/day, allopurinol start dose ≥300 mg/day, diabetes and female sex were associated with significantly higher hazard of HSRs, 1.27 (95% CI: 1.12 to 1.44), 1.21 (95% CI: 1.00 to 1.45) and 1.32 (95% CI: 1.17 to 1.48), respectively. The majority (69%) of HSRs occurred in the outpatient setting. CONCLUSIONS: Compared with colchicine, allopurinol and febuxostat similarly increased the risk of HSRs. Allopurinol and febuxostat did not differ from each other. In allopurinol users, starting dose, female sex and diabetes increased this risk, findings that need further study.

Assessment of effectiveness of anakinra and canakinumab in patients with colchicine-resistant/unresponsive familial Mediterranean fever

Abstract İntroduction: Familial Mediterranean fever (FMF) is a hereditary auto-inflammatory disease characterized by recurrent fever and serosal inflammation. Anti-interleukin-1 (Anti-IL-1) treatments are recommended in colchicine resistant and/or intolerant FMF patients. This study aims to evaluate the efficacy of anakinra and canakinumab in FMF patients that are resistant/intolareted to colchicine or complicated with amyloidosis. Methods: Between January 2014 and March 2019, 65 patients following-up at Sivas Cumhuriyet University (Medical Faculty Rheumatology-Internal Medicine Department) who were diagnosed with FMF according to the criteria of Tel-Hashomer were included in the study. The laboratory values and clinical features of patients and disease activities were recorded at least every 3 months, and these data were analyzed. Results: Forty-one (63.1%) patients used anakinra (100 mg/day) and 24 (36.9%) patients used canakinumab (150 mg/8 week). The median duration of anti-IL-1 agents use was 7 months (range, 3-30). Fifteen (23.1%) cases were complicated with amyloidosis. Seven (10.8%) patients had renal transplantation. Overall, the FMF 50 score response was 96.9%. In the group that had a glomerular filtration rate (GFR) ≥ 60 ml/min/m2, the median proteinuria decreased from 2390 mg/day (range, 1400-7200) to 890 mg/day (range, 120-2750) (p = 0.008). No serious infections were detected, except in one patient. Conclusions: Anti-IL-1 agents are effective and safe in the treatment of FMF patients. These agents are particularly effective at reducing proteinuria in patients with GFR ≥ 60 ml/min/m2, but less effective in cases with FMF associated with arthritis and sacroiliitis. Large and long follow-up studies are now needed to establish the long-term effects of these treatments.

Effects of colchicine on risk of cardiovascular events and mortality among patients with gout: a cohort study using electronic medical records linked with Medicare claims.

BACKGROUND: Colchicine may have beneficial effects on cardiovascular (CV) disease, but there are sparse data on its CV effect among patients with gout. We examined the potential association between colchicine and CV risk and all-cause mortality in gout. METHODS: The analyses used data from an electronic medical record (EMR) database linked with Medicare claims (2006-2011). To be eligible for the study cohort, subjects must have had a diagnosis of gout in the EMR and Medicare claims. New users of colchicine were identified and followed up from the first colchicine dispensing date. Non-users had no evidence of colchicine prescriptions during the study period and were matched to users on the start of follow-up, age and gender. Both groups were followed for the primary outcome, a composite of myocardial infarction, stroke or transient ischaemic attack. We calculated HRs in Cox regression, adjusting for potential confounders. RESULTS: We matched 501 users with an equal number of non-users with a median follow-up of 16.5 months. During follow-up, 28 primary CV events were observed among users and 82 among non-users. Incidence rates per 1000 person-years were 35.6 for users and 81.8 for non-users. After full adjustment, colchicine use was associated with a 49% lower risk (HR 0.51, 95% CI 0.30 to 0.88) in the primary CV outcome as well as a 73% reduction in all-cause mortality (HR 0.55, 95% CI 0.35 to 0.85, p=0.007). CONCLUSIONS: Colchicine use was associated with a reduced risk of a CV event among patients with gout.

Assessment of the association between colchicine therapy and serious adverse events.

STUDY OBJECTIVE: As data that prompted a 2009 labeling change detailing contraindications, precautions, and dosing recommendations for the first branded colchicine product were limited to case reports of myotoxicity and blood dyscrasias ascribed to the drug, we sought to quantify the association of colchicine therapy with serious adverse outcomes in a cohort of insured patients. DESIGN: Case-control study. DATA SOURCE: Kaiser Permanente Colorado electronic data warehouses and electronic medical records. PATIENTS: Cases were patients with a creatine kinase (CK) level of at least 2000 U/L or who developed a clinically significant non-cancer-related blood dyscrasia (thrombocytopenia, neutropenia, leukopenia, aplastic anemia, or pancytopenia) between January 1, 2006, and June 30, 2009 (954 cases). Each case was matched to up to 10 controls by age, sex, and index date (date of the increased CK level or blood dyscrasia-supporting laboratory value). Controls were patients without elevated CK levels or blood dyscrasias who had a routine health maintenance examination during the same time period (index date was the date of their health maintenance examination [9007 controls]). MEASUREMENTS AND MAIN RESULTS: The primary study outcome was colchicine exposure, defined as a colchicine prescription purchase in the 100 days before the index date. The likelihood of colchicine exposure was examined with conditional logistic regression. Cases experienced a higher rate of previous colchicine exposure compared with controls (0.6% vs 0.2%, odds ratio 3.9, 95% confidence interval 1.4-10.7). In addition, cases had higher hospitalization rates (14.9% vs 5.0%, p<0.001), higher mean chronic disease scores (2.5 vs 0.0, p<0.001), and were more likely to have been exposed to drugs that may increase the risk of adverse events due to an interaction with a CYP3A4 inhibitor drug (6.9% vs 2.3%, p<0.001). CONCLUSION: Patients with confirmed elevations in CK level and/or blood dyscrasias had a higher rate of previous colchicine exposure, although low overall, and greater hospitalization rates and exposure to drugs that may increase the risk of adverse events compared with controls. These findings support the 2009 United States Food and Drug Administration labeling for the first branded colchicine product, cautioning use in patients with liver impairment or renal dysfunction and/or those receiving concurrent drugs that may increase risk of adverse events.

Assessment of efficacy and psychomotor performances of thiocolchicoside and tizanidine in patients with acute low back pain.

Objectives of this study were to assess efficacy and effects on psychomotor performances of thiocolchicoside (TCC) and tizanidine (TZ) compared to placebo. Patients complaining of acute low back pain (LBP) associated with muscle spasm were enrolled in this randomised, double-blind clinical trial, comparing the effects of oral TCC, TZ and placebo on psychomotor performances assessed by a visual analogue scale of tiredness, drowsiness, dizziness and alertness and by psychometric tests after 2 and 5-7 days of treatment. The efficacy assessments, both TCC and TZ, were more effective than placebo in improving pain at rest, hand-to-floor distance, Schober test and decreased paracetamol consumption. There were significant differences among the treatment groups in favour of TCC compared to TZ in visual analog scale-parameters. TZ-induced reduction of psychomotor performances of the patients was confirmed by psychometric tests, which showed significant differences among groups. This study showed that TCC is at least as effective as TZ in the treatment of acute LBP, while it appears devoid of any sedative effect in contrast to TZ.

An unusual case of diarrhoea.

Case histories are based on actual medical negligence claims, however certain facts have been omitted or changed by the author to ensure the anonymity of the parties involved. Medication errors in general practice are relatively common. This article describes a medication error that led to a patient complaint and claim.