Jt Joensuu

The cost-effectiveness of biologics for the treatment of rheumatoid arthritis: a systematic review.

Background and Objectives Economic evaluations provide information to aid the optimal utilization of limited healthcare resources. Costs of biologics for Rheumatoid arthritis (RA) are remarkably high, which makes these agents an important target for economic evaluations. This systematic review aims to identify existing studies examining the cost-effectiveness of biologics for RA, assess their quality and report their results systematically. Methods A literature search covering Medline, Scopus, Cochrane library, ACP Journal club and Web of Science was performed in March 2013. The cost-utility analyses (CUAs) of one or more available biological drugs for the treatment of RA in adults were included. Two independent investigators systematically collected information and assessed the quality of the studies. To enable the comparison of the results, all costs were converted to 2013 euro. Results Of the 4890 references found in the literature search, 41 CUAs were included in the current systematic review. While considering only direct costs, the incremental cost-effectiveness ratio (ICER) of the tumor necrosis factor inhibitors (TNFi) ranged from 39,000 to 1 273,000 €/quality adjusted life year (QALY) gained in comparison to conventional disease-modifying antirheumatic drugs (cDMARDs) in cDMARD naïve patients. Among patients with an insufficient response to cDMARDs, biologics were associated with ICERs ranging from 12,000 to 708,000 €/QALY. Rituximab was found to be the most cost-effective alternative compared to other biologics among the patients with an insufficient response to TNFi. Conclusions When 35,000 €/QALY is considered as a threshold for the ICER, TNFis do not seem to be cost-effective among cDMARD naïve patients and patients with an insufficient response to cDMARDs. With thresholds of 50,000 to 100,000 €/QALY biologics might be cost-effective among patients with an inadequate response to cDMARDs. Standardization of multiattribute utility instruments and a validated standard conversion method for missing utility measures would enable better comparison between CUAs.

Rates of Serious Infections and Malignancies Among Patients with Rheumatoid Arthritis Receiving Either Tumor Necrosis Factor Inhibitor or Rituximab Therapy

Objective. Because of the role of tumor necrosis factor (TNF) in host defense, it was hypothesized that its inhibition might lead to an increased risk of malignancies and infections. The objective of our study was to assess the incidence of serious infections leading to hospitalization and malignancies among patients with rheumatoid arthritis (RA) receiving either TNF inhibitor or rituximab (RTX) therapy. Methods. The study population was identified from the National Register for Biologic Treatment in Finland and the hospital records of Central Finland Central Hospital for conventional disease-modifying antirheumatic drug (cDMARD) users. Data on infections and malignancies were acquired from national healthcare registers. A Poisson model was used to calculate the adjusted incidence rate ratios (aIRR) and was composed of age, sex, time from diagnosis, year of the beginning of the followup, rheumatoid factor status, Disease Activity Score at 28 joints, Health Assessment Questionnaire, prior malignancy, prior serious infection, prior biologic use, and time-updated use of methotrexate, sulfasalazine, hydroxychloroquine, and oral corticosteroids as confounders. Results. In total, during the followup of 10,994 patient-years, 92 malignancies and 341 serious infections were included in the analyses. The aIRR of infections compared to cDMARD users were 1.2 (95% CI 0.63–2.3), 0.84 (95% CI 0.53–1.3), 0.98 (95% CI 0.60–1.6), and 1.1 (95% CI 0.59–1.9) for the patients treated with infliximab (IFX), etanercept, adalimumab, and RTX, respectively. The crude rates of malignancies were highest among the users of cDMARD and RTX, and lowest among patients treated with IFX with no differences in aIRR. Conclusion. Our results provide some reassurance of the safety of biologic treatments in the treatment of RA.

Effectiveness and Drug Survival of TNF Inhibitors in the Treatment of Ankylosing Spondylitis: A Prospective Cohort Study

Objective. The aim of this research was to describe the effectiveness and drug survival of tumor necrosis factor (TNF) inhibitors in the treatment of ankylosing spondylitis (AS) and to analyze the effect of concomitant treatment with conventional disease-modifying antirheumatic drugs. Methods. Patients with AS identified from the National Register for Biologic Treatment in Finland starting their first TNF inhibitor treatment between July 2004 and December 2011 were included. Treatment response was measured as an improvement of 50% (or 20 mm) after 6 months of treatment onset compared to the baseline Bath AS Disease Activity Index (BASDAI) score. Treatment response and 2-year drug survival were modeled with logistic regression and time-dependent Cox proportional hazard models, respectively. Results. The study comprised 543 patients, of whom 123 also commenced a second TNF inhibitor during the followup. Treatment was discontinued within 24 months by 25% and 28% of the users of the first and the second TNF inhibitors, respectively. BASDAI response at 6 months was achieved by 52% and 25% of the users of the first and the second TNF inhibitors, respectively. Etanercept (ETN; HR 0.42, 95% CI 0.29–0.62) and adalimumab (ADA; HR 0.48, 95% CI 0.30–0.77) were associated with better drug survival in comparison to infliximab (IFX). Also, concurrent use of sulfasalazine (SSZ; HR 0.70, 95% CI 0.49–0.99) decreased the hazard for treatment discontinuation. Conclusion. TNF inhibitors are equipotent in the treatment of AS; however, ETN and ADA were found superior to IFX in drug survival. The use of SSZ improves treatment continuation.

Effectiveness and drug survival of TNF-inhibitors in the treatment of psoriatic arthritis: A prospective cohort study

BACKGROUND AND OBJECTIVES Tumor necrosis factor (TNF)-inhibitors are used to treat psoriatic arthritis (PsA), but only a limited number of observational studies on this subject have been published thus far. The aim of this research was to analyze the effectiveness and drug survival of TNF-inhibitors in the treatment of PsA. METHODS PsA patients identified from the National Register for Biologic Treatment in Finland (ROB-FIN) starting their first, second, or third TNF-inhibitor treatment between 2004 and 2014 were included. Effectiveness was measured using ACR and EULAR response criteria and modeled using ordinal logistic regression. Treatment persistence was analyzed using Kaplan-Meier survival analysis and Cox proportional hazards model. RESULTS The study comprised 765 patients and 990 TNF-inhibitor treatment courses. EULAR moderate treatment responses at 6 months were achieved by 68% and 37% of the users of the first and the second or the third biologic, respectively. The probabilities of discontinuing the treatment within 12 and 24 months were 20% and 28%, respectively. Adjusted treatment responses to all TNF-inhibitors were similar; however, co-therapy with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) was not associated with better effectiveness. Adalimumab [hazard ratio (HR) = 0.62; 95% confidence interval (CI): 0.44-0.88] was superior to infliximab in drug survival while etanercept (HR = 0.77, 95% CI: 0.55-1.1) and golimumab (HR = 0.75, 95% CI: 0.46-1.2) did not differ from it. Co-medication with csDMARDs did not statistically improve drug survival. CONCLUSION All available TNF-inhibitors showed similar treatment responses with or without csDMARDs. Adalimumab was associated with better drug survival when compared to infliximab.

Drug survival on tumour necrosis factor inhibitors in patients with rheumatoid arthritis in Finland.

Objective: A systematic review found that an average of 27% of rheumatoid arthritis (RA) patients using tumour necrosis factor (TNF) inhibitors discontinue their treatment within 1 year. The aim of this study was to assess drug survival on TNF inhibitors among patients with RA. Methods: Patients were identified from the National Register for Biologic Treatment in Finland (ROB-FIN), which is a longitudinal cohort study established to monitor the effectiveness and safety of biologic drugs in rheumatic diseases. Inclusion was limited to TNF-inhibitor treatments started as the patient’s first, second, or third biologic treatment between 2004 and 2014. Follow-up was truncated at 36 months. The results of a time-dependent Cox proportional hazards model were reported as adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Results: Of the 4200 TNF-inhibitor treatment periods identified from ROB-FIN, 3443 periods from 2687 patients met the inclusion criteria. Twenty-seven per cent of the patients discontinued their treatment within 12 months. Infliximab (HR 1.8, 95% CI 1.3–2.5) and certolizumab pegol (HR 1.7, 95% CI 1.2–2.3) had lower drug survival compared to golimumab. A similar trend was seen with adalimumab (HR 1.2, 95% CI 0.90–1.7) and etanercept (HR 1.2, 95% CI 0.87–1.6). Concomitant use of methotrexate (MTX) was associated with improved drug survival (HR 0.76, 95% CI 0.64–0.90) in comparison with TNF-inhibitor monotherapy. Conclusions: Golimumab was better in terms of drug survival than infliximab or certolizumab pegol and at least as good as adalimumab and etanercept. Concomitant use of MTX improved drug survival on TNF inhibitors.

Cost-effectiveness of biologic compared with conventional synthetic disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis: a Register study

OBJECTIVE The aim of this study was to explore the cost-effectiveness of biological DMARDs (bDMARDs) compared with conventional synthetic DMARDs (csDMARDs) for RA using real-world data from Finnish registers. METHODS RA patients starting their first bDMARD and comparator patients using csDMARDs during 2007-11 were obtained from the National register of biologic treatments in Finland and the Jyväskylä Central Hospital patient records. Propensity score matching was applied to adjust for differences between bDMARD and csDMARD users. Effectiveness was measured in quality-adjusted life years (QALY) and based on the register of biologic treatments in Finland and Jyväskylä Central Hospital patient records, whereas the direct costs were obtained from relevant Finnish national registers. Patients were followed up for 2 years, and both costs and effectiveness for the second year were discounted at 3%. The incremental cost-effectiveness ratio (ICER) with 95% CI was calculated based on bootstrapped mean costs and effectiveness. RESULTS Of 1581 RA patients meeting study inclusion criteria, 552 bDMARD and 220 csDMARD users were included in analyses after matching. Mean costs for bDMARDs and csDMARDs were €55 371 and €24 879, while mean effectiveness was 1.23 and 1.20 QALYs, respectively. Consequent ICER was €902 210/QALY. Results were confirmed in sensitivity analyses. CONCLUSION The high incremental cost and the small, non-significant difference in effectiveness resulted in high ICER, suggesting that bDMARDs are not cost-effective. Regardless of matching, latent confounders may introduce bias to the results.

THU0178 Rates of Serious Infections and Malignancies among Rheumatoid Arthritis Patients Receiving Either Tnf-Blocker or Rituximab Therapy in Finland

Background While randomized clinical trials have not showed an increased risk for serious infections among TNF-blocker users in comparison to methotrexate, we sought to confirm the results in Finnish routine care [1]. Objectives The objective of the study was to investigate the incidence of serious infections and malignancies among patients with rheumatoid arthritis (RA) using either TNF-blockers, rituximab or conventional disease modifying anti-rheumatic drugs (cDMARD). Methods Study protocol restricted inclusion to the current users of infliximab, etanercept, adalimumab or rituximab. Additionally, biologic-naïve cDMARD users were recruited as a control group. Furthermore, treatments prior to the first recorded out-patient specialized care visit were excluded from the analyses. The follow-up time included a six month lag-time to capture adverse events that occur after discontinuation but may have been due to the exposure. The study population was identified from the National Register of biological treatment in Finland (ROB-FIN) and from the hospital records of Jyväskylä Central Hospital, the latter providing all the cDMARD patients. Records on serious infections and malignancies were retrieved from the National Hospital Discharge Register and the National Cancer Register, respectively. Data from different registers were merged on the patient level using unique social security numbers. The results are presented as counts, incidence rates per 1000 patient-years (IR) and adjusted hazard ratios (HR) along with their respective 95% confidence intervals. The confounding factors included in the model comprised age, sex, disease activity, time from diagnosis, use of cortisone as well as prior infections and malignancies. Results The study comprised 3,542 patients accumulating 11,337 patient years, including switchers. Between 1999 and 2011 there were 100 (IR 31, 25-38), 179 (IR 24, 21-28; HR 0.9, 0.6-1.3) and 26 (IR 35, 23-51; HR 0.8, 0.4-1.5) serious infections in the DMARD, TNF-blocker and rituximab groups, respectively. The most common serious infections included erysipelas, sepsis, gastroenteritis, bronchitis along with tuberculosis. The results for new-onset malignancies among cDMARD, TNF-blocker and rituximab groups were 39 (IR 12, 9-17), 45 (IR 6, 4-8; HR 1.2, 0.67-2.4) and 7 (IR 9, 4-19; HR 0.7, 0.2-3.0), respectively. Conclusions Nor the unadjusted or adjusted results found evidence of increased risk for serious infections or malignancies among TNF-blocker or rituximab users compared to the cDMARD users. References Aaltonen KJ, Virkki LM, Malmivaara A, et al. Systematic Review and Meta-Analysis of the Efficacy and Safety of Existing TNF Blocking Agents in Treatment of Rheumatoid Arthritis. PLoS One 2012;7:e30275. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.2568

Biological treatment in ankylosing spondylitis in the Nordic countries during 2010–2016: a collaboration between five biological registries

Objectives: Large-scale observational cohorts may be used to study the effectiveness and rare side effects of biological disease-modifying anti-rheumatic drugs (bDMARDs) in ankylosing spondylitis (AS), but may be hampered by differences in baseline characteristics and disease activity across countries. We aimed to explore the research infrastructure in the five Nordic countries regarding bDMARD treatment in AS. Method: This observational cohort study was based on data from biological registries in Denmark (DANBIO), Sweden (SRQ/ARTIS), Finland (ROB-FIN), Norway (NOR-DMARD), and Iceland (ICEBIO). Data were collected for the years 2010–2016. Registry coverage, registry inventory (patient characteristics, disease activity measures), and national guidelines for bDMARD prescription in AS were described per country. Incident (first line) and prevalent bDMARD use per capita, country, and year were calculated. In AS patients who started first line bDMARDs during 2010–2016 (n = 4392), baseline characteristics and disease activity measures were retrieved. Results: Registry coverage of bDMARD-treated patients ranged from 60% to 95%. All registries included extensive prospectively collected data at patient level. Guidelines regarding choice of first line drug and prescription patterns varied across countries. During the period 2010–2016 prevalent bDMARD use increased (p < 0.001), whereas incident use tended to decrease (p for trend < 0.004), with large national variations (e.g. 2016 incidence: Iceland 10.7/100 000, Finland 1.7/100 000). Baseline characteristics were similar regarding C-reactive protein, but differed for other variables, including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (range 3.5–6.3) and Ankylosing Spondylitis Disease Activity Score (ASDAS) (2.7–3.8) (both p < 0.0001). Conclusion: Collaboration across the five Nordic biological registries regarding bDMARD use in AS is feasible but national differences in coverage, prescription patterns, and patient characteristics must be taken into account depending on the scientific question.

Cost-Effectiveness of Biologics Compared to Conventional Disease-Modifying Antirheumatic Drugs for Treatment of Rheumatoid Arthritis in Finland.

could influence the cost and quality of life of patients. To assess the cost-effectiveness of adding a PPI compared to no PPI co-treatment in older patients LDASA. Methods: A cost-effectiveness study was conducted with a Markov model for PPI co-medication (intervention) compared to no PPI co-medication (usual care) in LDASA users. The base case analysis was performed for patients of 70 years old. The models addressed chronic LDASA use of five years. Incremental cost-utility ratio’s (ICURs), expressed as costs per QALY gained, were calculated for different age categories (60 up to 80 years) accounting for different risk rates for side effects from LDASA or PPI use. These side effects included gastrointestinal bleeding, dyspepsia, pneumonia and hip fractures. Finally, a budget impact analysis was performed to assess the health care expenditures to add PPIs in all current patients using LDASA above the age of 60 years in the Netherlands. Results: Adding a PPI to LDASA, compared to not adding a PPI, resulted in incremental costs of € 71,84 and incremental effects of 0,006 QALY’s and an ICUR of € 11,491.53/QALY gained for the base case analysis. The ICUR for 60and 80-year old patients was € 11,491.53/QALY and € 53,860.85/QALY, respectively. The total budget impact of adding a PPI to current LDASA users (≥ 60 years) was € 174,475,296. ConClusions: Adding a PPI to LDASA users may be a cost-effective approach in patients from 60 up to 80 years old. However, with increasing age the costs became higher and the effects lower, due to higher risks of the different side effects.