Correction: Low dose naltrexone: Effects on medication in rheumatoid and seropositive arthritis. A nationwide register-based controlled quasi-experimental before-after study.
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ABSTRACT:
SUBMITTER: Raknes G
PROVIDER: S-EPMC6772034 | biostudies-literature | 2019
REPOSITORIES: biostudies-literature
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Correction: Low dose naltrexone: Effects on medication in rheumatoid and seropositive arthritis. A nationwide register-based controlled quasi-experimental before-after study.
Raknes Guttorm G Småbrekke Lars L
PloS one 20191001 10
[This corrects the article DOI: 10.1371/journal.pone.0212460.]. ...[more]
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Project description:In recent years, low dose naltrexone (LDN) has been used as an off-label therapy for several chronic diseases. Results from small laboratory and clinical studies indicate some beneficial effects of LDN in autoimmune diseases, but clinical research on LDN in rheumatic disease is limited. Using a pharmacoepidemiological approach, we wanted to test the hypothesis that starting LDN leads to reduced dispensing of medicines used in the treatment of rheumatic disease. We performed a controlled before-after study based on the Norwegian Prescription Database (NorPD) to compare prescriptions to patients one year before and one year after starting LDN in 2013. The identified patients (n = 360) were stratified into three groups based on LDN exposure. Outcomes were differences in dispensing of medicines used in rheumatic disease. In persistent LDN users, there was a 13% relative reduction in cumulative defined daily doses (DDD) of all medicines examined corresponding to -73.3 DDD per patient (95% CI -120,2 to -26.4, p = 0.003), and 23% reduction of analgesics (-21.6 DDD (95% CI -35.5 to -7.6, p<0.009)). There was no significant DDD change in patients with lower LDN exposure. Persistent LDN users had significantly reduced DDDs of NSAID and opioids, and a lower proportion of users of DMARDs (-6.7 percentage points, 95% CI -12.3 to-1.0, p = 0.028), TNF-? antagonists and opioids. There was a decrease in the number of NSAID users among patients with the least LDN exposure. Important limitations are that prescription data are proxies for clinical effects and that a control group unexposed to LDN is lacking. The results support the hypothesis that persistent use of LDN reduces the need for medication used in the treatment of rheumatic and seropositive arthritis. Randomised clinical trials on LDN in rheumatic disease are warranted.
| S-EPMC6375629 | biostudies-literature
Project description:Our objective was to estimate the risk of developing rheumatoid arthritis (RA) associated with a family history of non-RA arthritis-related diseases. This familial co-aggregation is of clinical interest since it is often encountered when assessing family history of RA specifically, but also informative on the genetic overlap between these diseases. Since anticitrullinated peptide antibodies/rheumatoid factor (RF)-positive and RF-negative RA have both specific and shared genetic factors, the familial co-aggregation was assessed separately for seropositive and seronegative disease.Nested case-control study in prospectively recorded Swedish total population data. The Multi-Generation Register identified first-degree relatives. RA and arthritis-related diseases were ascertained through the nationwide patient register. RA serology was based on International Classification of Diseases tenth revision coded diagnoses, mainly reflecting RF. Familial risks were calculated using conditional logistic regression. Results were replicated using the Swedish rheumatology register.Familial co-aggregation was found between RA and every studied arthritis-related disease, but the magnitude varied widely, from juvenile idiopathic arthritis (JIA) (seropositive RA OR=3.98 (3.01 to 5.26); seronegative RA OR=5.70 (3.47 to 9.36)) to osteoarthritis (seropositive RA OR=1.03 (1.00 to 1.06); seronegative RA OR=1.05 (1.00 to 1.09)). The familial co-aggregation pattern of non-RA arthritis-related diseases was overall similar for seropositive and seronegative RA. Among those with family history of RA, relatives' other arthritis-related diseases conferred little or no additional risk.Although family history of several arthritis-related diseases may be useful to predict RA (eg, lupus and JIA), others (eg, osteoarthritis and arthralgia) are less useful. Seropositive and seronegative RA had rather similar familial co-aggregation patterns with arthritis-related diseases, suggesting that the two RA subsets are similar in the genetic factors that overlap with these diseases.
| S-EPMC4465879 | biostudies-literature
Project description:The purpose of this longitudinal follow-up study was to investigate the risk of ischemic stroke nationwide in patients with seropositive rheumatoid arthritis (RA) and controls who were matched in age and sex. Patient data were collected from the National Health Insurance Service (NHIS) Health Screening (HEALS) cohort. Using the International Classification of Diseases code M05 (seropositive RA), with a prescription of any disease-modifying anti-rheumatic drug (DMARD), RA was identified. A total of 2,765 patients and 13,825 control subjects were included in our study. The 12-year incidence of ischemic stroke in each group was calculated using the Kaplan-Meier method. The risk ratio of ischemic stroke was estimated using Cox proportional hazards regression. Sixty-four patients (2.31%) in the seropositive RA group and 512 (3.70%) in the control group experienced ischemic stroke (P < 0.001) during the follow-up period. The hazard ratio of ischemic stroke in the seropositive RA group was 1.32 (95% confidence interval (CI), 1.02-1.73) after adjusting for age and sex. The adjusted hazard ratio of ischemic stroke in the seropositive RA group was 1.40 (95% CI, 1.07-1.82) after adjusting for demographics and comorbid medical disorders. According to the subgroup analysis, the hazard ratios of ischemic stroke risks in the female and hypertensive subgroups were 1.44 (95% CI, 1.05-1.97) and 1.66 (95% CI, 1.16-2.38), respectively. In the non-diabetes and non-dyslipidemia subgroups, the corresponding hazard ratios of ischemic stroke were 1.47 (95% CI, 1.11-1.95) and 1.43 (95% CI, 1.07-1.91). Seropositive RA patients have an increased risk of ischemic stroke. In female, hypertension, non-diabetes, and non-dyslipidemia RA subgroups, even without the traditional risk factors for stroke (except for hypertension), increased the risk, which could be potentially attributed to RA.
| S-EPMC8128246 | biostudies-literature
Project description:Background and Aims:Low-dose naltrexone [LDN] is a controversial off-label treatment used by many Crohn's disease [CD] and ulcerative colitis [UC] patients. A small number of preliminary studies indicate that LDN might be beneficial in CD, but evidence is too scarce to demonstrate efficacy. We sought to examine whether initiation of LDN therapy by patients with inflammatory bowel disease [IBD] was followed by changes in dispensing of relevant medication. Methods:We performed a quasi-experimental before-and-after study following a sudden increase in LDN use in the Norwegian population in 2013. IBD patients were identified from among all the patients who had at least one LDN prescription recorded in the Norwegian Prescription Database [NorPD] in 2013. Drug dispensing 2 years before and after the first LDN prescription was compared. Results :We identified 582 IBD patients who had received LDN. Of the 256 patients who became persistent LDN users, there were reductions in the number of users for [i] all examined drugs [-12%], [ii] intestinal anti-inflammatory agents [-17%], [iii] other immunosuppressants [-29%], [iv] intestinal corticosteroids [-32%] and [v] aminosalicylates [-17%]. In subgroups of identified CD and UC patients, there were significant reductions in the number of users of intestinal corticosteroids [CD: -44%, UC: -53%] and systemic corticosteroids [UC: -24%]. No significant differences in cumulative defined daily doses were observed. Conclusions :Our findings imply that the initiation of LDN in IBD is followed by reduced dispensing of several drugs considered essential in the treatment of CD and UC.
| S-EPMC5972567 | biostudies-literature
Project description:BACKGROUND:We investigated the mortality and disability rate, as well as the healthcare expenditure, for patients with newly diagnosed seropositive rheumatoid arthritis (RA) who were followed-up for up to 10 years, compared to the general population in Korea. METHODS:We conducted a nationwide population-based study using a National Health Insurance Service-National Sample Cohort of the Korean population, consisting of 1 million individuals who submitted medical care claims between 2002 and 2013. RA was identified using as the International Classification of Diseases code M05 (seropositive RA), with prescription of any disease-modifying anti-rheumatic drug (DMARD). Our analysis was based on the data of 1655 patients with incident seropositive RA and 8275 non-RA controls. The controls were matched to the RA cohort by sex, age at the time of diagnosis, duration of follow-up, geographic region, type of social security, and household income. RESULTS:The most commonly used conventional synthetic DMARDs were hydroxychloroquine (71.30%) and methotrexate (69.5%), with adalimumab being the most commonly used biologic DMARD (2.54%). The mortality rate was significantly higher in the RA than the control group (incidence rate ratio [IRR] 1.29, 95% confidence interval [CI] 1.02-1.64) in the first 10 years after diagnosis. Specifically, mortality due to infectious diseases (IRR 4.41, 95% CI 1.60-12.17) and pneumonia (IRR 3.92, 95% CI 1.46-10.53) was significantly higher in the RA than control group. The disability rate was higher in the RA than control group over the first 10 years of the disease (IRR 2.27, 95% CI 1.77-2.92), which was attributed to a higher incidence of physical disability (IRR 3.81, 95% CI 2.81-5.15). Annual health expenditure was greater for the RA than the control group. CONCLUSIONS:Therefore, the rate of mortality and disability, as well as healthcare expenditure, are higher for patients with RA over the first 10 years of the disease onset, than the general population of Korea. The use of claim data has limited the quality of information and there is a limit to the observation period, and we expect the prospective national-wide multicenter cohort for longer period to overcome these limitations.
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Project description:We described the case of a 23-year-old Nepalese man with seropositive rheumatoid arthritis and abnormal x-ray findings, found to be due to a very rare bone disease: Camurati Engelmann disease or progressive diaphyseal dysplasia (PDD). This is the first case reported in the Gulf area, although approximately 300 cases have been described worldwide. These patients usually present with limb pain and easy fatigability. Our patient first presented with bilateral, symmetrical inflammatory polyarthritis involving the knees, ankles and wrists but sparing the hands and feet. The diagnosis of PDD in our case was based on the classic radiological findings and a bone scan. LEARNING POINTS:Rheumatoid arthritis is a common condition with typical radiological findings.Any unusual radiological finding should be carefully assessed and explained.In our case the unusual findings were due to progressive diaphyseal dysplasia.
| S-EPMC6346779 | biostudies-literature
Project description:Low dose naltrexone (LDN) has become a popular off-label therapy for multiple sclerosis (MS). A few small, randomized studies indicate that LDN may have beneficial effects in MS and other autoimmune diseases. If proven efficacious, it would be a cheap and safe alternative to the expensive treatments currently recommended for MS. We investigated whether a sudden increase in LDN use in Norway in 2013 was followed by changes in dispensing of other medications used to treat MS. We performed a quasi-experimental before-and-after study based on population data from the Norwegian Prescription Database (NorPD). We included all patients that collected at least one LDN prescription in 2013, and had collected at least two medications with a reimbursement code for MS, or collected a medication with MS as the only indication in 2009 or 2010. Outcomes were differences in cumulative dispensed doses and incidence of users of disease modifying MS therapies, and medications used to treat MS symptoms two years before and two years after dispensing the initial LDN prescription. The eligible 341 patients collected 20 921 prescriptions in the observation period. Apart from changes in line with general trends in MS therapy in Norway, there was no difference in neither dispensed cumulative doses or number of prevalent users of MS specific medication. Initiation of LDN was not followed by reductions of other medications used to treat symptoms associated with MS.
| S-EPMC5669439 | biostudies-literature
Project description:Recent discoveries of risk alleles have made it possible to define genetic risk profiles for patients with rheumatoid arthritis (RA). This study examined whether a cumulative score based on 22 validated genetic risk alleles for seropositive RA would identify high-risk, asymptomatic individuals who might benefit from preventive interventions.Eight human leucocyte antigen (HLA) alleles and 14 single-nucleotide polymorphisms representing 13 validated RA risk loci were genotyped among 289 white seropositive cases and 481 controls from the US Nurses' Health Studies (NHS) and 629 white cyclic-citrullinated peptide antibody-positive cases and 623 controls from the Swedish Epidemiologic Investigation of Rheumatoid Arthritis (EIRA). A weighted genetic risk score (GRS) was created, in which the weight for each risk allele is the log of the published odds ratio (OR). Logistic regression was used to study associations with incident RA. Area under the curve (AUC) statistics were compared from a clinical-only model and clinical plus genetic model in each cohort.Patients with GRS >1.25 SD of the mean had a significantly higher OR of seropositive RA in both NHS (OR=2.9, 95%CI 1.8 to 4.6) and EIRA (OR 3.4, 95% CI 2.3 to 5.0) referent to the population average. In NHS, the AUC for a clinical model was 0.57 and for a clinical plus genetic model was 0.66, and in EIRA was 0.63 and 0.75, respectively.The combination of 22 risk alleles into a weighted GRS significantly stratifies individuals for RA risk beyond clinical risk factors alone. Given the low incidence of RA, the clinical utility of a weighted GRS is limited in the general population.
| S-EPMC2933175 | biostudies-literature
Project description:Both rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) are associated with poor radiologic outcomes in patients with rheumatoid arthritis (RA). In general, RA patients positive for RF or ACPA (SPRA) are considered to manifest an aggressive disease course compared with seronegative RA patients (SNRA). However, the relationship between seropositivity and measures of disease severity other than radiologic outcome is disputed. In this study, we sought to compare the clinical presentations and treatment outcomes of SNRA and SPRA patients. A total of 241 patients diagnosed with DMARD-naïve RA under either 1987 American College of Rheumatology (ACR) criteria or 2010 ACR/European League Against Rheumatism (EULAR) criteria were identified (40 with SNRA and 201 with SPRA). We investigated the disease activity measures including ESR, CRP, patient VAS, 28 tender/swollen joint count (28 TJC, 28 SJC) and DAS28 as well as radiologic outcomes at baseline, 1 and 2 years after conventional treatment with DMARD. Age, sex and disease duration were similar between SNRA and SPRA. However, the baseline 28 TJC (4.7±2.9 vs. 3.3±2.7, p = 0.004), 28 SJC (4.3±3.0 vs. 2.9±2.3, p = 0.001) and DAS28 (5.1±1.0 vs. 4.7±1.0, p = 0.043) components were significantly higher in SNRA than in SPRA. Over 2 years of similar treatment with DMARDs, all disease activity measures significantly improved in both groups. Comparison among populations matched for baseline disease activity showed that ?DAS28 at 1 year was greater in SNRA than in SPRA (-2.84±1.32 vs. -3.70±1.29, p = 0.037) in high disease activity population (DAS28-ESR>5.1). Radiologic outcomes at baseline and at 1- or 2-year follow-up were similar between the 2 groups. In conclusion, SNRA patients manifested more active disease at baseline, but showed a better response to treatment compared with SPRA. SNRA does not appear to be a benign subtype of RA.
| S-EPMC5889180 | biostudies-literature
Project description:BACKGROUND:Human cytomegalovirus (HCMV) seropositivity has been associated with higher inflammation during rheumatoid arthritis (RA). However, no data are available on the impact of HCMV seropositivity on bone erosion progression during RA. METHODS:We selected 487 individuals of ESPOIR cohort who fulfilled the 2010 ACR/EULAR criteria for RA. HCMV serology for these patients was determined using Architect CMV IgG assay. Baseline and 1-year central X-ray reading using modified Total Sharp Score (mTSS), Erosion Sharp Score, and joint space narrowing Sharp score were used to quantify structural damage progression. We performed univariate and multivariate analyses to investigate the association between HCMV status and bone erosion progression. RESULTS:We analyzed 273 HCMV seropositive (HCMV+) and 214 HCMV seronegative (HCMV-) RA patients. At inclusion, HCMV+ patients were less frequently ACPA+ (49.8% versus 58.9%, p < 0.0465) and had a higher DAS28-ESR (5.55 ± 1.24 versus 5.20 ± 1.14, p < 0.0013) in comparison with HCMV-. At 1 year, bone erosion progression (delta erosion Sharp score > 1 point) was lower in HCMV+ patients (16.1% versus 25.2%, p = 0.0128) in comparison with HCMV-. HCMV+ status remained independently associated with lower bone erosion progression in multivariate analysis. CONCLUSIONS:Our findings suggest that, independently of other confounding factors, HCMV seropositivity is associated with a lower progression of bone erosion during RA.
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