The influence of biological DMARDs on aseptic arthroplasty loosening: a retrospective cohort study.

OBJECTIVE: To investigate whether biological DMARDs affect the risk of aseptic loosening after total hip/knee arthroplasty (THA/TKA) in patients with RA. METHODS: We retrospectively identified all patients suffering from RA who underwent THA/TKA at our academic centre between 2002 and 2015 and linked them with an existing prospective observational RA database at our institution. The risk of aseptic loosening was estimated using radiological signs of component loosening (RCL). A time-dependent Cox regression analysis was used to compare the risk of implant loosening between patients treated with traditional DMARDS and biological DMARDs, or alternately both over time. RESULTS: A total of 155 consecutive total joint arthroplasties (TJAs) (103 TKA vs 52 THA) was retrospectively included in the study. Mean age at implantation was 59 ± 13 years. Mean follow-up time was 69 ± 43 months. Overall, 48 (31%) TJAs showed signs of RCL, with 28 (27.2%) RCLs occurring after TKA compared with 20 after THA (38.5%). A significant difference regarding the incidence of RCL between the traditional DMARDs group (39 cases of RCL, 35%) and the biological DMARDs group (nine cases of RCL, 21%) (P = 0.026) was observed using the log-rank test. This was also true when using a time-dependent Cox regression with therapy as well as arthroplasty location (hip vs knee) as variables (P = 0.0447). CONCLUSION: Biological DMARDs may reduce the incidence of aseptic loosening after TJA in patients with RA compared with traditional DMARDs. This effect seems to be more pronounced after TKA than THA.

"Long-term MRI findings in Ankylosing spondylitis patients treated with TNF inhibitors for a decade".

OBJECTIVE: This study aims to evaluate the active and chronic lesions in sacroiliac joints and lumbar spine over a decade of TNFi therapy in patients with AS. METHODS: The study enrolled patients with AS under treatment with a TNFi for over a decade. The patients underwent a new MRI scan of their lumbar spine and sacroiliac joint (SIJ). Two readers evaluated all images. Inflammation of SIJ (SIS), SIJ structural damage (SSS) including Fat Metaplasia, Erosions, Backfill and Ankylosis, and Spondyloarthritis Research Consortium of Canada Bone marrow edema (SPARCC) spine score were recorded. RESULTS: In the study, 15 patients were included, with 80% being male. The mean age during their first MRI was 38.1 (± 11.9) years old, and the majority (86.7%) tested positive for HLA-B27. While TNFi improved both BASDAI and BASFI scores, there was a noticeable increase in MRI acute lesions in the SIJ over time, where the median score increased from 0 (0-4) to 3 (0-10) after ten years (p = 0.028). After a decade of treatment, the median SPARCC spine score also increased from 0 (0-9) to 5 (0-16), p = 0.093. Finally, it was observed that there was a significant positive correlation between ESR and SIS erosions in cases of chronic lesions (r = 0.819, p < 0.001). CONCLUSIONS: While TNFi have significantly improved the treatment of AS, this study shows that acute lesions can still develop despite treatment. A personalized approach that adapts MRI assessment to each patient's specific requirements may help detect changes early and enable doctors to intervene promptly to prevent further damage.

Systematic review for the treatment of older rheumatoid arthritis patients informing the 2024 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis.

OBJECTIVES: To update an evidence base informing the 2024 JCR clinical practice guidelines (CPGs) for the management of rheumatoid arthritis (RA) in older adults. METHODS: Four clinical questions (CQs) regarding efficacy and safety of drug treatment were evaluated, with CQ1 addressing methotrexate (MTX), CQ2 biological disease-modifying antirheumatic drugs (bDMARDs), CQ3 Janus kinase (JAK) inhibitors, and CQ4 glucocorticoids (GCs). Quality of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system. RESULTS: Observational studies confirmed a pivotal role of MTX in the treatment of older RA patients. The meta-analysis showed that tumor necrosis factor inhibitors and JAK inhibitors were unequivocally effective in older RA patients. No data indicated that bDMARDs were unsafe for older patients. No safety data for JAK inhibitor use in older patients were available. One randomized controlled trial demonstrated that long-term treatment with low-dose GCs increased risks of GC-associated adverse events. The certainty of overall evidence was very low for all CQs. CONCLUSION: This systematic review provides the necessary evidence for developing 2024 JCR CPGs for managing older patients with RA. Continued updates on the evidence of JAK inhibitors and GC are desired.

Evaluation of the Synovial Effects of Biological and Targeted Synthetic DMARDs in Patients with Psoriatic Arthritis: A Systematic Literature Review and Meta-Analysis.

The aims of this systematic literature review (SLR) were to identify the effects of approved biological and targeted synthetic disease modifying antirheumatic drugs (b/tsDMARDs) on synovial membrane of psoriatic arthritis (PsA) patients, and to determine the existence of histological/molecular biomarkers of response to therapy. A search was conducted on MEDLINE, Embase, Scopus, and Cochrane Library (PROSPERO:CRD42022304986) to retrieve data on longitudinal change of biomarkers in paired synovial biopsies and in vitro studies. A meta-analysis was conducted by adopting the standardized mean difference (SMD) as a measure of the effect. Twenty-two studies were included (19 longitudinal, 3 in vitro). In longitudinal studies, TNF inhibitors were the most used drugs, while, for in vitro studies, JAK inhibitors or adalimumab/secukinumab were assessed. The main technique used was immunohistochemistry (longitudinal studies). The meta-analysis showed a significant reduction in both CD3+ lymphocytes (SMD -0.85 [95% CI -1.23; -0.47]) and CD68+ macrophages (sublining, sl) (SMD -0.74 [-1.16; -0.32]) in synovial biopsies from patients treated for 4-12 weeks with bDMARDs. Reduction in CD3+ mostly correlated with clinical response. Despite heterogeneity among the biomarkers evaluated, the reduction in CD3+/CD68+sl cells during the first 3 months of treatment with TNF inhibitors represents the most consistent variation reported in the literature.

Socioeconomic impact of treatment with biological disease-modifying antirheumatic drugs in Japanese patients with rheumatoid arthritis.

OBJECTIVES: We evaluate the socioeconomic impact of treatment with biological and targeted synthetic disease-modifying antirheumatic drugs in Japanese patients with rheumatoid arthritis. METHODS: We analysed data retrospectively from the prospective observational CorEvitas RA Japan Registry (March 2016-February 2020). Patients were categorised into paid workers (PWs) and home workers (HWs) and further based on drug classes. We assessed medication persistence, treatment outcomes, health care resource utilisation, and socioeconomic impact over 12 months, including direct (drugs and health care resource utilisation) and indirect (loss of productivity) costs. RESULTS: Overall, 187 PWs and 114 HWs were identified. Over 12 months, medication persistence was high, treatment outcomes improved, and outpatient visits reduced in both groups. Following treatment initiation, direct costs increased, whereas indirect (loss of productivity) costs decreased in both groups. The unadjusted socioeconomic impact [Japanese yen (JPY)] increased across all drug classes in PWs (range: 29,700-151,700) and HWs (range: -28,700 to 83,000). Adjusted change in monthly socioeconomic impact was JPY 29,700-138,900 for PWs and JPY -28,000 to 92,800 for HWs. CONCLUSIONS: In this study of Japanese patients with rheumatoid arthritis, the socioeconomic burden increased across patient groups and drug classes. The decrease in indirect (loss of productivity) costs partially offset the increase in direct costs.

Response to secukinumab on synovitis using Power Doppler ultrasound in psoriatic arthritis: 12-week results from a phase III study, ULTIMATE.

OBJECTIVES: To investigate the dynamics of response of synovitis to IL-17A inhibition with secukinumab in patients with active PsA using Power Doppler ultrasound. METHODS: The randomized, placebo-controlled, Phase III ULTIMATE study enrolled PsA patients with active ultrasound synovitis and clinical synovitis and enthesitis having an inadequate response to conventional DMARDs and naïve to biologic DMARDs. Patients were randomly assigned to receive either weekly subcutaneous secukinumab (300 or 150 mg according to the severity of psoriasis) or placebo followed by 4-weekly dosing thereafter. The primary outcome was the mean change in the ultrasound Global EULAR and OMERACT Synovitis Score (GLOESS) from baseline to week 12. Key secondary endpoints included ACR 20 and 50 responses. RESULTS: Of the 166 patients enrolled, 97% completed 12 weeks of treatment (secukinumab, 99%; placebo, 95%). The primary end point was met, and the adjusted mean change in GLOESS was higher with secukinumab than placebo [-9 (0.9) vs -6 (0.9), difference (95% CI): -3 (-6, -1); one-sided P=0.004] at week 12. The difference in GLOESS between secukinumab and placebo was significant as early as one week after initiation of treatment. All key secondary endpoints were met. No new or unexpected safety findings were reported. CONCLUSION: This unique ultrasound study shows that apart from improving the signs and symptoms of PsA, IL-17A inhibition with secukinumab leads to a rapid and significant reduction of synovitis in PsA patients. TRIAL REGISTRATION: ClinicalTrials.gov; NCT02662985.

Rheumatoid arthritis with nontuberculous mycobacterial pulmonary disease: a retrospective, single-centre cohort study.

OBJECTIVES: Nontuberculous mycobacterial pulmonary disease (NTM-PD) is a rare but important comorbidity of rheumatoid arthritis (RA). Our objective was to investigate the association between NTM-PD and RA, especially regarding the immunosuppressive treatment of RA such as biological disease-modifying antirheumatic drugs (bDMARDs). METHODS: We conducted a retrospective, single-centre cohort study. All RA patients regularly followed up at our rheumatology division in December 2012 were included in the study, and followed for 5 years. RESULTS: At baseline, 26 of 1639 RA patients had NTM-PD. During the observation period, 14 were newly diagnosed with NTM-PD. For new diagnosis of NTM-PD, bDMARD use at baseline was not a significant risk factor. Among the 40 patients with NTM-PD, 16 were treated with a total of 27 bDMARDs after NTM-PD diagnosis. They did not present with a greater exacerbation of NTM-PD than those not treated with bDMARDs (25 vs. 17%, p = .52). A total of 55 patients died, but nobody died of NTM-PD. NTM-PD was not associated with worse mortality in multivariate analysis (hazard ratio, 2.0; 95% CI, 0.6-6.4; p = .26). CONCLUSIONS: Biological DMARD was not associated with worse prognosis of NTM-PD. Careful use of bDMARDs could be tolerated in RA patients with NTM-PD.

Factors associated with impaired physical function in elderly rheumatoid arthritis patients who had achieved low disease activity.

OBJECTIVE: We aimed to investigate factors associated with impaired physical function (defined as HAQ Disability Index [HAQ-DI] >0.5) of old-old (aged 75-84) patients with rheumatoid arthritis (RA). METHODS: Data from 15,185 RA patients in the National Database of Rheumatic Disease in Japan were extracted from 2017 to 2018. We enrolled 3,708 patients aged 55-84 in simplified disease activity index (SDAI) ≤11 and Steinbrocker stage I/II. Factors associated with HAQ-DI >0.5 were analyzed by multivariable logistic regression. RESULTS: About half of the old-old patients received methotrexate, which was lower than middle-aged (55-64) and young-old patients (65-74). The proportion of glucocorticoids in the old-old patients was highest among the three groups, and biological disease-modifying anti-rheumatic drugs were similarly used. The prevalence of HAQ-DI >0.5 was significantly higher in old-old patients with low disease activity than in those with remission. The same was true in the middle-aged and young-old patients. Multivariable analysis showed age, higher SDAI, glucocorticoid use, and methotrexate non-use were significantly associated with HAQ-DI >0.5 in the old-old patients. CONCLUSIONS: SDAI remission was an ideal goal for old-old patients in terms of physical function. Glucocorticoids and a low proportion of methotrexate use may influence the physical function of old-old patients.

Treatment strategies for elderly-onset rheumatoid arthritis in the new era.

Elderly-onset rheumatoid arthritis (EORA) is characterized by acute onset and clinical features of high disease activity. Anti-cyclic citrullinated peptide antibody (ACPA) positivity or the presence of bone erosions predicts a radiological joint destruction of EORA, but ACPA-negative EORA with a polymyalgia rheumatica (PMR) phenotype may also present. Biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors were beneficial both in older and in younger patients in terms of risk-benefit balance. Implementation of a treat-to-target strategy could improve EORA outcomes, but older patients have more age-related comorbidities and interstitial lung disease than younger patients. Baseline comorbidities, more frequent methotrexate dose-dependent adverse events, serious infections, cardiovascular disease events, and malignancy all influence the choice of treatment and the treatment goals for older patients. Based on articles reviewed here, it is suggested that current treatment strategies for younger patients are also useful for ACPA-positive EORA and for ACPA-negative EORA with bone erosion. Differential diagnosis of ACPA-negative EORA without erosive arthritis and PMR with peripheral manifestations is challenging, and the treatment strategy of patients presenting with this overlap phenotype remained unclear. An appropriate treatment strategy for all patients with EORA still needs to be developed.

Systematic review for the treatment of older rheumatoid arthritis patients informing the 2020 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis.

OBJECTIVES: To provide an evidence base for clinical practice guidelines (CPG) for the management of rheumatoid arthritis (RA) in older adults. METHODS: PubMed, Cochrane library, and Japan Centra Revuo Medicina databases were searched for articles published between 1990 and 2019. Quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation system, with some modifications. RESULTS: Among 702 identified articles, there were 5 post-hoc analyses of randomized controlled trials and 10 observational studies. Meta-analysis of the former yielded a mean difference of the van der Heijde-modified total Sharp score of -2.79 (95% confidence interval [CI] - 3.74 to -1.84) for treatment with tumor necrosis factor inhibitors. The risk ratio (RR) for the American College of Rheumatology 50% response rate, and for serious adverse events was 2.83 (95%CI 1.90-4.21) and 1.32 (95%CI 0.53-3.31), respectively, for Janus kinase inhibitors. Meta-analysis of the observational studies yielded an RR for disease activity score-28 remission and serious infections of 0.76 (95%CI 0.64-0.91) and 1.92 (95%CI 1.31-2.81) for older-versus-younger patients receiving biological disease-modifying antirheumatic drugs, respectively. CONCLUSION: This systematic review provides the necessary evidence for developing CPG for the management of RA in older adults.

Trabecular and cortical bone involvement in rheumatoid arthritis by DXA and DXA-based 3D modelling.

Rheumatoid arthritis (RA) patients had a higher risk of developing low bone mineral density (BMD) or osteoporosis. RA patients on classic disease-modifying antirheumatic drug (c-DMARD) therapy showed significantly lower BMD than controls, while no significant differences in most parameters were found between RA patients receiving biological disease-modifying antirheumatic drugs (b-DMARDs) and controls. The 3D analysis allowed us to find changes in the trabecular and cortical compartments. INTRODUCTION: To evaluate cortical and trabecular bone involvement of the hip in RA patients by dual-energy X-ray absorptiometry (DXA) and 3D analysis. The secondary end-point was to evaluate bone involvement in patients treated with classic (c-DMARD) or biological (b-DMARD) disease-modifying antirheumatic drug therapies and the effect of the duration of the disease and corticosteroid therapy on 3D parameters. METHODS: A cross-sectional study of 105 RA patients and 100 subjects as a control group (CG) matched by age, sex, and BMI was carried out. BMD was measured by DXA of the bilateral femoral neck (FN) and total hip (TH). The 3D analyses including trabecular and cortical BMD were performed on hip scans with the 3D-Shaper software. RESULTS: FN and TH BMD and trabecular and cortical vBMD were significantly lower in RA patients. The c-DMARD (n = 75) group showed significantly lower trabecular and cortical vBMD than the CG. Despite the lower values, the b-DMARD group (n = 30) showed no significant differences in most parameters compared with the CG. The trabecular and cortical 3D parameters were significantly lower in the group with an RA disease duration of 1 to 5 years than in the CG, and the trabecular vBMD was significantly lower in the group with a duration of corticosteroid therapy of 1 to 5 years than in the CG, while no significant differences were found by standard DXA in the same period. CONCLUSIONS: RA patients had a higher risk of developing low BMD or osteoporosis than controls. RA patients receiving c-DMARD therapy showed significantly lower BMD than controls, while no significant differences in most parameters were found between RA patients receiving b-DMARDs and controls. 3D-DXA allowed us to find changes in trabecular and cortical bone compartments in RA patients.

A rapid monitoring plan following a shift in coverage from brand name to biosimilar drugs for rheumatoid arthritis in British Columbia.

PURPOSE: To describe a rapid monitoring plan to assess the impacts of a shift in drug coverage for biosimilar drugs in British Columbia following the introduction of a new policy on 27 May 2019. The Biosimilars Initiative requires users of originator infliximab or etanercept to switch to biosimilar versions of those drugs to maintain coverage. We propose a signal-detection method to provide near-real-time information to policymakers on the impacts of the policy change. METHODS: The exposure will be the Biosimilars Initiative, a policy affecting patients using originator infliximab (Remicade) and etanercept (Enbrel) for approved rheumatologic or dermatologic indications. Two policy cohorts and six historical control cohorts of patients using originator infliximab or etanercept will be assembled using linked and de-identified data from the British Columbia Ministry of Health. Patients will be identified during the 6-month period before the policy anniversary. Outcomes will include medication refills and switching, hospital admissions, emergency department visits, and physician visits. Summary outcome measures, such as cumulative incidence or average quantity as applicable, will be examined daily and reported monthly for 1 year. Outcomes in the policy cohorts will be compared with historical controls using likelihood ratios. RESULTS: The results of this rapid monitoring plan will be based on analyses involving approximately 9000 patients: four infliximab cohorts of approximately 430 patients and four etanercept cohorts of approximately 1800 patients. CONCLUSIONS: Rapid monitoring results will inform ongoing policy decisions related to the Biosimilars Initiative, in terms of impacts on both patient health and health services utilization.

Rapid monitoring of health services utilization following a shift in coverage from brand name to biosimilar drugs in British Columbia-An interim report.

PURPOSE: We explored changes in health services utilization associated with the Biosimilars Initiative introduced in British Columbia on May 27, 2019. To maintain drug coverage, the policy requires users of originator infliximab or etanercept to transition to biosimilar versions. We present a three-month interim analysis of this initiative. METHODS: We conducted a rapid monitoring analysis to evaluate changes in health services utilization three months after the policy was introduced compared with a three-year period before the policy's introduction. Using the administrative claims data of the British Columbia Ministry of Health, we assembled three historical cohorts and one policy cohort of users of each originator drug (8 cohorts in total). Cumulative incidences of medication refills, switching, and visits to physicians were the outcome measures used to compare policy and historical cohorts. Likelihood ratios were used to quantify statistical differences between each policy cohort and its respective historical controls. Likelihood ratios above 7.1 were considered statistically significant. RESULTS: The four infliximab cohorts included 436 patients on average, mean age 56 to 59, 53% to 55% females. The four etanercept cohorts included 1826 patients on average, mean age 57 to 58, 60% to 63% females. Three months after the policy's introduction, 21% of patients treated in the policy cohorts transitioned to the biosimilar versions. Health services utilization in the policy cohorts were consistent with the historical cohorts. CONCLUSIONS: An increase in visits to physicians was expected but not detected in the first three months of the Biosimilars Initiative. The impacts of the policy will continue to be monitored.

Leukocytapheresis for rheumatoid arthritis cases that are super-resistant to any class of biological drugs and tofacitinib.

Many biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) are currently available as treatment options for rheumatoid arthritis (RA), but a subset of RA patients shows inadequate responses to any of these DMARDs. This phenomenon, which we call super-resistance, is becoming a serious concern. In this study, I present two cases of super-resistant RA in which patients failed to respond to treatment with bDMARDs of any class as well as to tsDMARD therapy with tofacitinib. In these cases, leukocytapheresis (LCAP), a treatment that removes overabundant leukocytes from the body, rapidly induced low disease activity and made patients subsequently responsive to previously ineffective DMARDs. My experience with the present cases suggests that LCAP is worth considering as an alternative therapeutic option for the management of RA patients with super-resistance to DMARD therapies.

Clinical effectiveness and long-term retention of abatacept in elderly rheumatoid arthritis patients: Results from a multicenter registry system.

Objective: To study the clinical effectiveness and long-term retention rate of abatacept (ABA) in elderly rheumatoid arthritis (RA) patients in daily clinical practice.Methods: A retrospective cohort study was performed using data from a multicenter registry. Our study population comprised 500 consecutive RA patients treated with ABA. We compared clinical effectiveness and ABA retention rates between the Young (≤62 years), Middle (62 to 72 years), and Elderly (≥72 years) groups. We also performed separate examinations to identify predictive factors for ABA discontinuation in those with versus those without concomitant methotrexate (MTX) treatment.Results: Mean age was 52.7 years in the Young group, 67.7 years in the Middle group, and 78.1 years in the Elderly group. No significant group-dependent differences were found in mean DAS28 score, categorical distribution of DAS28, and EULAR response rate across the 52 weeks. The ABA retention rates at three years as determined by the Kaplan-Meier method were similar in all three groups. Patient age was not a significant predictor of ABA discontinuation due to adverse events in patients with concomitant MTX; however, it was found to be a significant predictor for those who did not use MTX (Cox hazard model).Conclusion: ABA would be a reasonable treatment option for elderly RA patients from the viewpoints of both clinical effectiveness and long-term retention. However, physicians should watch carefully for any serious adverse reactions in elderly RA patients with intolerance to MTX.

Predictive factors for structural remission using abatacept: Results from the ABROAD study.

OBJECTIVE: To investigate the effect of abatacept (ABA) on preventing joint destruction in biological disease-modifying anti-rheumatic drug (bDMARD)-naïve rheumatoid arthritis (RA) patients in real-world clinical practice. PATIENTS AND METHODS: RA patients were collected from the ABROAD (ABatacept Research Outcomes as a First-line Biological Agent in the Real WorlD) study cohort. They had moderate or high disease activity and were treated with ABA as a first-line bDMARD. Radiographic change between baseline and 1 year after ABA treatment was assessed with the van der Heijde's modified Total Sharp Score (mTSS). Predictive factors for structural remission (St-REM), defined as ΔmTSS ≤0.5/year, were determined. RESULTS: Among 118 patients, 81 (67.5%) achieved St-REM. Disease duration <3 years (odds ratio (OR) = 3.152, p = .007) and slower radiographic progression (shown as 'baseline mTSS/year <3', OR = 3.727, p = .004) were independently significant baseline predictive factors for St-REM irrespective of age and sex. St-REM prevalence increased significantly if clinical remission based on the Simplified Disease Activity Index was achieved at least once until 24 weeks after ABA treatment. CONCLUSION: Shorter disease duration, smaller radiographic progression at baseline, and rapid clinical response were predictive factors for sustained St-REM after ABA therapy in bDMARD-naïve RA patients.

Serious infusion-related reaction after rituximab, abatacept and tocilizumab in rheumatoid arthritis: prospective registry data.

Objective: The aim was to evaluate the incidence of serious infusion-related reactions (SIRRs) in RA treated by non-TNF-targeted biologics. Methods: We analysed data from three independent prospective registers, namely autoimmunity and rituximab, Orencia (abatacept) and RA (ORA) and Registry RoAcTEmra (tocilizumab), promoted by the French Society of Rheumatology and including patients with RA. SIRRs were defined by an occurrence during or within 24 h of an infusion and requiring discontinuation of treatment. Characteristics of patients with SIRRs were extracted from the electronic database. Results: Among the 4145 patients, SIRRs occurred in 100 patients: 56 patients with the rituximab cohort (2.8% or 0.7/100 patient-years), 15 with the abatacept cohort (1.5% or 0.6/100 patient-years) and 29 with tocilizumab (1.9% or 1/100 patient-years). No fatal SIRR occurred. A previous mild infusion reaction to non-TNF-targeted biologics was observed in a quarter of patients with SIRRs. After pooled multivariate analysis, positive anti-CCP was associated with a higher risk of SIRR (odds ratio = 2.5; 95% CI: 1.01, 6.17). Absence of concomitant treatment with a synthetic DMARD tended to be associated with a higher risk of SIRR (odds ratio = 1.67; 95% CI: 1.00, 2.86). Conclusion: In daily practice, SIRRs are slightly more frequent than in clinical trials and rarely life threatening. In common practice, serological status (anti-CCP positivity) and absence of concomitant treatment with a synthetic DMARD increase the risk of SIRR.

Safety and effectiveness of tacrolimus add-on therapy for rheumatoid arthritis patients without an adequate response to biological disease-modifying anti-rheumatic drugs (DMARDs): Post-marketing surveillance in Japan.

OBJECTIVES: Post-marketing surveillance (PMS) was conducted to assess the safety and effectiveness of tacrolimus (TAC) add-on therapy for patients with rheumatoid arthritis (RA) and an inadequate response to biological disease-modifying anti-rheumatic drugs (DMARDs). METHODS: Patients with RA from 180 medical sites across Japan were registered centrally with an electronic investigation system. The observational period was 24 weeks from the first day of TAC administration concomitantly with biological DMARDs. RESULTS: Safety and effectiveness populations included 624 and 566 patients, respectively. Patients were predominantly female (81.1%), with a mean age of 61.9 years. Overall, 125 adverse drug reactions (ADRs) occurred in 94 patients (15.1%), and 15 serious ADRs occurred in 11 patients (1.8%). These incidences were lower compared with previously reported incidences after TAC treatment in PMS, and all of the observed ADRs were already known. A statistically significant improvement was observed in the primary effectiveness variable of Simplified Disease Activity Index after TAC treatment; 62.7% of patients achieved remission or low disease activity at week 24. CONCLUSIONS: TAC is well tolerated and effective when used as an add-on to biological DMARDs in Japanese patients with RA who do not achieve an adequate response to biological DMARDs in a real-world clinical setting.

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.

Risk factors for surgical site infection and delayed wound healing after orthopedic surgery in rheumatoid arthritis patients.

OBJECTIVE: To investigate the prevalence and the risk factors of surgical-site infection (SSI) and delayed wound healing (DWH) in patients with rheumatoid arthritis (RA) underwent orthopedic surgery. METHODS: We reviewed the records of 1036 elective orthopedic procedures undertaken in RA patients. Risk factors for SSI and DWH were assessed by logistic regression analysis using age, body mass index, disease duration, pre-operative laboratory data, surgical procedure, corticosteroid use, co-morbidity, and use of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and biological DMARDs (bDMARDs) as variables. RESULTS: SSI and DWH were identified in 19 cases and 15 cases, respectively. One case of SSI and three cases of DWH were recorded among 196 procedures in patients using bDMARDs. Foot and ankle surgery was associated with an increased risk of SSI (odds ratio (OR), 3.167; 95% confidence interval (CI), 1.256-7.986; p = 0.015). Total knee arthroplasty (TKA; OR, 4.044; 95% CI, 1.436-11.389; p = 0.008) and disease duration (OR, 1.004; 95% CI, 1.000-1.007; p = 0.029) were associated with an increased risk of DWH. CONCLUSIONS: Our results indicated foot and ankle surgery, and TKA and disease duration as risk factors for SSI and DWH, respectively. bDMARDs was not associated with an increased risk of SSI and DWH.