Disease-modifying Antirheumatic Drugs In Patients Research Articles

P122 Secular trends in prescription of biologic and targeted synthetic disease-modifying anti-rheumatic drugs in rheumatoid arthritis: Experience from a UK regional centre (2016-2022)

Abstract Background/Aims In the past two decades, biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs) have substantially transformed the treatment landscape for rheumatoid arthritis (RA). With the emergence of new molecules, the introduction of cost-effective biosimilars, and the impact of the COVID pandemic, the treatment preferences might have shifted over time. We aim to explore the evolving trends in the prescription of biologic and targeted synthetic DMARDs in RA patients whose disease was refractory to conventional DMARDs. Methods A biologic registry was set up sourcing data from pharmacy and departmental records. Data of RA patients who were commenced on biologics or targeted synthetic DMARDs between January 2016 and December 2022 are presented descriptively without formal statistical assessments. Line plots depict prescription trends over the years. Data visualization done using R studio (v 2023.06). Results We have 1504 out of the 2345 patients in our biologic registry with RA; 827 of these patients commenced the treatment in the 7-year study period. Over the years, biosimilars are increasingly being preferred as the first-line agents. If a biosimilar for a biologic drug was available, all prescriptions were for the biosimilar in 2022. There was a significant drop (43.7%) in biologic prescriptions during the pandemic in 2020 compared to the previous year. However, by the next year, prescriptions rebounded to 91% of their pre-pandemic levels. TNF inhibitors and Janus kinase (JAK) inhibitors were the most common treatments initiated. There was a steady increase in the prescription of JAK inhibitors since their introduction in 2017. During the pandemic, JAK inhibitors were the most preferred agents for RA. However, a decline in their prescriptions was noted in 2022, down 36% from the previous year, possibly due to emerging concerns about their cardiovascular safety. While there was reduction in prescription of all biologics during pandemic, anti B cell therapy had the steepest decline (74.1% reduction in 2020 compared to previous year). This may be due to the increased risk of SARS-CoV-2 infection and impaired response to the vaccine with Rituximab. This trend is gradually reversing. Rates of prescription of abatacept and anti-IL6 agents remained fairly stable across the seven years. Conclusion Significant fluctuations are evident in the trend of prescription of biologic and targeted synthetic DMARDs in patients with rheumatoid arthritis in a regional centre in UK. We conclude that availability of biosimilars, safety data on JAK inhibitors and impact of the COVID pandemic had influenced the prescription trends. Disclosure H. Muhammed: None. H. Osborn: None. K. Hughes: None. A. Yau: None. G. Hirsch: None. S. Raizada: None. T. Sheeran: None. S. Venkatachalam: None.

Non-Invasive Assessment of Micro- and Macrovascular Function after Initiation of JAK Inhibitors in Patients with Rheumatoid Arthritis.

Janus kinase (JAK) inhibitors constitute a novel class of oral biologic disease-modifying antirheumatic drugs for patients with rheumatoid arthritis (RA). However, their use has been associated with increased risk of major cardiovascular events. We investigated whether treatment with JAK inhibitors exerts significant alterations in the micro- and microvasculature in RA patients. Thirteen patients with RA initiating treatment with JAK inhibitors were prospectively studied. Eventually, data from 11 patients who completed the study were analyzed. Procedures were performed at baseline and 3 months after treatment. Nailfold videocapillaroscopy was applied to detect alterations of the dermal capillary network. Participants underwent 24 h ambulatory blood pressure monitoring (Mobil-O-Graph device) for the assessment of blood pressure (both brachial and aortic) and markers of large artery stiffening [pulse wave velocity (PWV), augmentation index] throughout the whole 24 h and the respective day- and nighttime periods. Carotid intima-media thickness was assessed with ultrasound. Three-month treatment with JAK inhibitors was not associated with any differences in brachial and aortic blood pressure, arterial stiffness, and carotid atherosclerosis, with the only exception of nighttime PWV, which was significantly elevated at follow-up. However, three-month treatment with JAK inhibitors induced significant microvascular alterations and increased the total number of capillaroscopic abnormalities. Three-month treatment with JAK inhibitors may exert significant effects on microcirculation as assessed with nailfold videocapillaroscopy, whereas macrovascular structure and function appears largely unaffected. Further research toward this direction may add substantial information to the available literature regarding cardiovascular aspects of JAK inhibitors in RA.

Comparison of retention of biologics in Japanese patients with elderly-onset rheumatoid arthritis-the ANSWER cohort study.

This multicentre, retrospective study aimed to compare retention and reasons for discontinuation between Janus kinase inhibitors (JAKi) and biologic disease-modifying antirheumatic drugs in patients with elderly-onset rheumatoid arthritis (EORA). Patients with RA enrolled in a Japanese multicentre observational registry between 2015 and 2022 were included. EORA was defined as RA with onset at 60 or over. To adjust confounding factors by indication for initiation of tumor necrosis factor inhibitors (TNFi), interleukin-6 inhibitors (IL-6i), cytotoxic T-lymphocyte associated antigen 4 immunoglobulin (CTLA4-Ig) blockers, or JAKi, a propensity score based on baseline characteristics was used to compare drug retention. To assess the reasons for discontinuation, retention rates for ineffectiveness, adverse events, and remission were analyzed as secondary outcomes. A total of 572 patients with 835 treatment courses were identified (314 TNFi, 175 IL-6i, 228 CTLA4-Ig, and 118 JAKi). After adjusting for differences in baseline characteristics, drug retention was significantly higher for IL-6i (HR = 0.38, 95%CI = 0.27-0.55, p< 0.01) as compared with TNFi. Discontinuation due to lack of effectiveness was lower with the JAKi (HR = 0.38, 95%CI = 0.22-0.66, p< 0.01) and the IL-6i (HR = 0.29, 95%CI = 0.19-0.46, p< 0.01) as compared with the TNFi although the CTLA4-Ig had a similar HR to TNFi. The adjusted incidence of discontinuation due to adverse event was higher in the JAKi (HR = 2.86, 95%CI = 1.46-5.59, p< 0.01) than the TNFi. In EORA patients, IL-6i and JAKi had longer retention and less discontinuation due to ineffectiveness than TNFi. The potential risks of JAKi should be approached with an individualized perspective.

Predictors at diagnosis for start of biologic disease-modifying antirheumatic drugs in patients with early rheumatoid arthritis: a cohort study

ObjectivesTo investigate the relation between patient characteristics at rheumatoid arthritis (RA) diagnosis and subsequent initiation of treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs).DesignA retrospective cohort...

HSD34 Real-World Usage of Biologic Disease-Modifying Anti-Rheumatic Drugs in Patients with Axial Spondyloarthritis in Germany

HSD34 Real-World Usage of Biologic Disease-Modifying Anti-Rheumatic Drugs in Patients with Axial Spondyloarthritis in Germany

HSD60 Real-World Usage of Biologic Disease-Modifying Anti-Rheumatic Drugs in Patients with Psoriatic Arthritis in Germany

HSD60 Real-World Usage of Biologic Disease-Modifying Anti-Rheumatic Drugs in Patients with Psoriatic Arthritis in Germany

Cardiovascular risk of Janus kinase inhibitors compared with biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis without underlying cardiovascular diseases: a nationwide cohort study.

Objectives: Despite the ethnic differences in cardiovascular (CV) risks and recent increase in the prescription of Janus kinase (JAK) inhibitors, limited evidence is available for their CV outcomes in Asian patients with rheumatoid arthritis (RA). We aimed to compare the major adverse CV events (MACEs) of JAK inhibitors to those of biologic disease-modifying antirheumatic drugs (bDMARDs) in Korean patients with RA without baseline CV disease (CVD). Methods: In a nationwide retrospective cohort study, patients newly diagnosed with RA without a history of CVD between 2013 and 2018 were identified using the National Health Insurance Service database. The cohort was followed up until the end of 2019 for the development of MACEs. Hazard ratios (HRs) for MACEs such as myocardial infarction, stroke, coronary revascularization, or all-cause death, were estimated using Cox proportional hazard regression in a propensity score-matched cohort. Results: In total, 4,230 matched patients with RA were included (846 JAK inhibitor users and 3,384 bDMARD users). The crude incidence rate (95% confidence intervals, CI) per 100 patient-years for MACEs was 0.83 (0.31-1.81) and 0.74 (0.53-1.02) in the JAK inhibitor and bDMARD groups, respectively. The risk of MACEs was not significantly different between JAK inhibitor and bDMARD users with an adjusted HR (95% CI) of 1.28 (0.53-3.11). There were no significant differences in the risk of MACEs between JAK inhibitors and bDMARDs in each subgroup according to the types of bDMARDs, age, sex, Charlson comorbidity index score, and comorbidities. Conclusion: Compared to bDMARDs, JAK inhibitors were not associated with the occurrence of MACEs in Korean patients with RA without a history of CVD.

Comparative effectiveness of JAK inhibitors and biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis.

We aimed to compare the effectiveness and safety of Janus kinase inhibitors (JAKi) vs. biologic disease- modifying antirheumatic drugs (bDMARD) in Korean patients with rheumatoid arthritis (RA) who had an inadequate response to conventional synthetic DMARDs. A quasi-experimental, multi-center, prospective, non-randomized study was conducted to compare response rates between JAKi and bDMARDs in patients with RA naïve to targeted therapy. An interim analysis was performed to estimate the proportion of patients achieving low disease activity (LDA) based on disease activity score (DAS)-28- erythroid sedimentation rate (ESR) (DAS28-ESR) at 24 weeks after treatment initiation and to evaluate the development of adverse events (AEs). Among 506 patients enrolled from 17 institutions between April 2020 and August 2022, 346 (196 JAKi group and 150 bDMARD group) were included in the analysis. After 24 weeks of treatment, 49.0% of JAKi users and 48.7% of bDMARD users achieved LDA (p = 0.954). DAS28-ESR remission rates were also comparable between JAKi and bDMARD users (30.1% and 31.3%, respectively; p = 0.806). The frequency of AEs reported in the JAKi group was numerically higher than that in the bDMARDs group, but the frequencies of serious and severe AEs were comparable between the groups. Our interim findings reveal JAKi have comparable effectiveness and safety to bDMARDs at 24 weeks after treatment initiation.

Cancer risks with JAKi and biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis or psoriatic arthritis: a national real-world cohort study

ObjectiveAssess cancer risks with Janus kinase inhibitors (JAKi) versus biological disease-modifying antirheumatic drugs (bDMARDs) in clinical practice.MethodsCohort study of patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA) initiating treatment...

The First Effect of COVID-19 Pandemic on Starting Biological Disease Modifying Anti-Rheumatic Drugs: Outcomes from the TReasure Real-Life Database.

The coronavirus disease 2019 pandemic has been resulting in increased hospital occupancy rates. Rheumatic patients cannot still reach to hospitals, or they hesitate about going to a hospital even they are able to reach. We aimed to show the effect of the first wave of coronavirus disease 2019 pandemic on the treatment of biological disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis or spondyloarthritis. Patients were divided into three groups as follows: pre-pandemic (Pre-p: starting on biological disease-modifying anti-rheumatic drug therapy for the first time within 6 months before March 11, 2020); post-pandemic A (Post-p A: starting on biological disease-modifying anti-rheumatic drug therapy for the first time within the first 6 months after March 11, 2020); post-pandemic B (Post-p B: starting on biological disease-modifying anti-rheumatic drug therapy for the first time within the second 6 months). The number of rheumatoid arthritis patients in the Post-p A and B groups decreased by 51% and 48%, respectively, as compared to the Pre-p group similar rates of reduction were also determined in the number of spondyloarthritis patients. The rates of tofacitinib and abatacept use increased in rheumatoid arthritis patients in Post-p period. The number of rheumatoid arthritis and spondyloarthritis patients starting on biological disease-modifying anti-rheumatic drugs for the first time decreased during the first year of the coronavirus disease 2019 pandemic.

Real-world patient characteristics and use of disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis: a cross-national study

IntroductionRheumatoid arthritis (RA) is associated with significant morbidity and economic burden. This study aimed to compare baseline characteristics and patterns of anti-inflammatory drug use and disease-modifying anti-rheumatic drug (DMARD) use among patients with RA in Southern Italy versus the United States.MethodUsing Caserta Local Health Unit (Italy) and Optum’s de-identified Clinformatics® Data Mart (United States) claims databases, patients with ≥ 2 diagnosis codes for RA during the study period (Caserta: 2010–2018; Optum: 2010–2019) were identified. Baseline patient characteristics, as well as proportion of RA patients untreated/treated with NSAIDs/glucocorticoids/conventional DMARDs (csDMARDs)/biological/targeted synthetic DMARDs (b/tsDMARDs) during the first year of follow-up, and the proportion of RA patients with ≥ 1 switch/add-on between the first and the second year of follow-up, were calculated. These analyses were then stratified by age group (< 65; ≥ 65).ResultsA total of 9227 RA patients from Caserta and 195,951 from Optum databases were identified (two-thirds were females). During the first year of follow-up, 45.9% RA patients from Optum versus 79.9% from Caserta were exclusively treated with NSAIDs/glucocorticoids; 17.2% versus 11.3% from Optum and Caserta, respectively, were treated with csDMARDs, mostly methotrexate or hydroxychloroquine in both cohorts. Compared to 0.6% of RA patients from Caserta, 3.2% of the Optum cohort received ≥ 1 b/tsDMARD dispensing. Moreover, 61,655 (33.7%) patients from Optum cohort remained untreated compared to 748 (8.3%) patients from the Caserta cohort. The subgroup analyses stratified by age showed that 42,989 (39.8%) of elderly RA patients were untreated compared to 18,666 (24.9%) young adult RA patients in Optum during the first year of follow-up. Moreover, a higher proportion of young adult RA patients was treated with b/tsDMARDs, with and without csDMARDs, compared to elderly RA patients (Optum<65: 6.4%; Optum≥65: 1.0%; P-value < 0.001; Caserta<65: 0.8%; Caserta≥65: 0.1%; P-value < 0.001). Among RA patients untreated during the first year after ID, 41.2% and 48.4% RA patients from Caserta and Optum, respectively, received NSAIDs, glucocorticoids, and cs/b/tsDMARDs within the second year of follow-up. Stratifying the analysis by age groups, 50.6% of untreated young RA patients received study drug dispensing within the second year of follow-up, compared to only 36.7% of elderly RA patients in Optum. Interestingly, more young adult RA patients treated with csDMARDs during the first year after ID received a therapy escalation to b/tsDMARD within the second year after ID in both cohorts, compared to elderly RA patients (Optum<65: 7.8%; Optum≥65: 1.8%; Caserta<65: 3.2%; Caserta≥65: 0.6%).ConclusionsMost of RA patients, with heterogeneous baseline characteristics in Optum and Caserta cohorts, were treated with anti-inflammatory/csDMARDs rather than bDMARDs/tsDMARDs during the first year post-diagnosis, especially in elderly RA patients, suggesting a need for better understanding and dealing with barriers in the use of these agents for RA patients.Key Points• Substantial heterogeneity in baseline characteristics and access to bDMARD or tsDMARD drugs between RA patients from the United States and Italy exists.• Most of RA patients seem to be treated with anti-inflammatory/csDMARD drugs rather than bDMARD/tsDMARD drugs during the first year post-diagnosis.• RA treatment escalation is less frequent in old RA patients than in young adult RA patients.• An appropriate use of DMARDs should be considered to achieve RA disease remission or low disease activity.

Efficacy of synthetic and biological DMARDs: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis

ObjectivesTo update the evidence on efficacy of DMARDs (disease-modifying antirheumatic drugs) and inform the taskforce of the 2022 update of the European Alliance of Associations for Rheumatology (EULAR) recommendations for...

Correlation of Clinical Disease Activity Score with Ultrasound Disease Activity Score in Rheumatoid Arthritis Patients of Kashmir Valley

Abstract Background: Musculoskeletal ultrasound can aid in assessing disease activity and deciding to taper off disease-modifying antirheumatic drugs in patients of rheumatoid arthritis (RA). With this background, we conducted a study to compare Clinical Disease Activity Score 28 C-reactive protein (DAS28 CRP) with Ultrasound Disease Activity Score 28 CRP (USDAS28 CRP) and its correlation with disease parameters in RA patients. Materials and Methods: Forty-eight RA patients were subjected to clinical and ultrasound assessment of disease activity after subjecting them to history, clinical, and laboratory investigations. The clinical assessment was done by DAS28 CRP and the US assessment was done by USDAS28 CRP score. The swollen joint count and the tender joint count were replaced by GSUS (grayscale ultrasound) score and power Doppler ultrasound score, respectively, in USDAS28 CRP score. Results: The mean age of the patients was 46.31 ± 13.90 years, with a mean duration of illness being 98.3 months. Nineteen patients had inactive disease and 29 patients had active disease on clinical examination. Six out of 19 (31.6%) patients with the inactive disease on clinical assessment had activity (subclinical synovitis) on US assessment. Two out of 29 (6.89%) patients with the active disease on clinical assessment had inactive disease on US assessment. Patients with subclinical synovitis had a longer disease duration (154 ± 114.2 vs. 73.38 ± 54.9 months, P = 0.05) and higher erythrocyte sedimentation rate (28.5[23] vs. 15[5] mm/H, P = 0.017) as compared to RA patients with the inactive disease on US assessment. Correlations between clinical scales and ultrasound scales were good (Pearson’s r = 0.832, P = 0.01). Conclusion: US scoring for disease assessment is a plausible method to assess subclinical activity in RA patients with inactive disease.

Efficacy and safety of progressively reducing biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis in persistent remission: a study protocol for a non-inferiority randomized, controlled, single-blind trial

BackgroundTo compare the effects of two biologic disease-modifying antirheumatic drug (bDMARD) administration strategies on the maintenance effect and safety of patients with rheumatoid arthritis (RA) in remission, to analyze the effects of gradual drug reduction and dose maintenance treatment on clinical outcomes in patients who have achieved remission with different types of bDMARDs, to search and screen out people who may benefit from drug reduction strategies, and to provide references for drug reduction strategies and treatment options for patients with RA in remission, so as to help improve the safety of the treatment and reduce the economic burden.MethodsThe study will be a 24-month non-inferiority randomized, controlled, single-blind trial and is planned to be launched in our hospital from September 2021 to August 2023. Patients will be randomized in a ratio of 2:1 to two groups: maintenance or injection spacing by 50%/gradual reduction of dosage every 3 months up to complete stop. When the patient relapses, return to the last effective dose. If the remission can be maintained, the medication of bDMARDs can be stopped 9 months after enrollment. The primary outcome will be the persistent flare rate.DiscussionOur study may provide a reference for the selection of drug reduction strategies and treatment options for patients with RA in remission, so as to help improve the safety of the treatment and reduce the economic burden.Trial registrationChinese Clinical Trial Registry ChiCTR2100044751. Registered on 26 March 2021

Trends of adverse events and mortality after DMARDs in patients with rheumatoid arthritis: Interrupted time-series analysis.

ObjectivesPatients with rheumatoid arthritis (RA) experience adverse events because of the characteristics of the disease and the side effects of medications. We investigated the trends of adverse events and mortality associated with disease‐modifying antirheumatic drugs (DMARDs).MethodsWe used the Taiwan National Health Insurance Database to enroll patients with incident RA between 2000 and 2017. The 1‐year incident rate of gastrointestinal (GI) bleeding and 3‐year incident rates of other adverse events and mortality for each calendar‐quarter cohort were computed and adjusted using propensity score‐based stabilized weights for fair comparisons. Levels and trends of the conventional DMARD era (2000–2002, Phase 1) were compared with those of the TNFi era (2003–2012, Phase 2) and OMA era (2013–2017, Phase 3) by using interrupted time series (ITS) analysis.ResultsAll patients with RA were prescribed cDMARDs in Phase 1 (2000–2002), and 1%–3% were prescribed either TNFi in phase 2 (2003–2012) or OMAs in phase 3 (2013–2017). The cancer incidence rate was 1.90%, and its mortality rate was 4.19%. After the introduction of TNFi from 2003 to 2012, the main outcomes, except TKA, exhibited a steady or mild decrease in trends. ITS analysis revealed that the slope mildly increased in 2003–2012 compared with that in 2000–2003 by 0.13% for total knee replacement (p = .0322). In 2012–2017 (the OMA era), the events became steady.ConclusionIn patients with RA, the introduction of DMARDs was associated with stable adverse events and mortality rates. Moreover, the introduced new treatment for RA exhibited a good safety profile.

A real-life analysis of patients with rheumatologic diseases on biological treatments: Data from TURKBIO Registry.

TURKBIO registry, established in 2011, is the first nationwide biological database in Turkey. This study aimed to provide an overview of TURKBIO data collected by June 2018. The registry included adult patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), nonradiographic axial spondyloarthritis (nr-AxSpA), and psoriatic arthritis (PsA). Demographic and clinical features, disease activity markers, and other follow-up parameters, current and previous treat- ments, and adverse events were registered electronically at each visit using open-source software. The registration of patient-reported outcome measures was carried out electronically by the patients using touch screens. TURKBIO registry included a total of 41,145 treatment series with biologicals. There were 2,588 patients with axSpA (2,459 AS and 129 nr-axSpA), 2,036 with RA, and 428 with PsA. The total number of patients, including those with other diagnoses, was 5,718. In the follow-up period, the number of patients and also visits steadily increased by years. The yearly mean number of visits per patient was found to be 2.3. Significant improvements in disease activity and health assessment parameters were observed following the biological treatments. Biologics were often given in combination with a con- ventional synthetic disease-modifying antirheumatic drug in patients with RA. Infections were the most commonly seen adverse events, followed by allergic reactions. Tuberculosis was observed in 12 patients, malignancy in 18, and treatment-related mortality in 31. TURKBIO provided a valuable real-life experience with the use of biologics in rheumatic diseases in Turkey.

Oral Conventional Synthetic Disease-Modifying Antirheumatic Drugs with Antineoplastic Potential: a Review.

There is an increasing trend of malignancy worldwide. Disease-modifying antirheumatic drugs (DMARDs) are the cornerstones for the treatment of immune-mediated inflammatory diseases (IMIDs), but risk of malignancy is a major concern for patients receiving DMARDs. In addition, many IMIDs already carry higher background risks of neoplasms. Recently, the black box warning of malignancies has been added for Janus kinase inhibitors. Also, the use of biologic DMARDs in patients with established malignancies is usually discouraged owing to exclusion of such patients in pivotal studies and, hence, lack of evidence. In contrast, some conventional synthetic DMARDs (csDMARDs) have been reported to show antineoplastic properties and can be beneficial for patients with cancer. Among the csDMARDs, chloroquine and hydroxychloroquine have been the most extensively studied, and methotrexate is an established chemotherapeutic agent. Even cyclosporine A, a well-known drug associated with cancer risk, can potentiate the effect of some chemotherapeutic agents. We review the possible mechanisms behind and clinical evidence of the antineoplastic activities of csDMARDs, including chloroquine and hydroxychloroquine, cyclosporine, leflunomide, mycophenolate mofetil, mycophenolic acid, methotrexate, sulfasalazine, and thiopurines. This knowledge may guide physicians in the choice of csDMARDs for patients with concurrent IMIDs and malignancies.

Clinical and economic analysis of biologic agents and targeted synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis: cost per responder model

AIM. To compare the cost per responder (CPR) between different groups of biologic agents and targeted synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis (RA). Materials and Methods. A total of 320 patients with RA were included in the study. Patients were divided into 4 groups (n=80 in each group): group 1 received B cell-depleting agent (rituximab), group 2 – TNF-alpha (α) inhibitors, group 3 –interleukin-6 inhibitor (tocilizumab), and group 4 – Janus kinase inhibitor (tofacitinib). The effectiveness of therapy was assessed using the generally accepted index of rheumatoid arthritis activity DAS28 and the dynamics of this index after 12 months of therapy. A good response on DAS28 (current DAS28 scores of 3.2 or less with reductions in DAS28 of more than 1.2) was accepted as a response to therapy. For the leading CPR-DAS28 drugs, an ad- ditional CPR study was performed using the SDAI, CDAI, and RAPID-3 indices. Results. A good response on DAS28 was observed more frequently in group 3 (56.3%) and group 4 (6.3%) compared to group 1 (11.5%, p&lt;0.05 in both cases) and group 2 patients (22.5%, p&lt;0.05 in both cases). CPR-DAS28 in group 3 was RUB 1094772.6, in group 4 – RUB 1089201.3; and that was 3.3 times lower than in group 1 (RUB 3587662.2, p&lt;0.05 in both cases) and 2.3 times lower than in group 4 (RUB 2545747.3, p&lt;0.05 in both cases). In group 3 (tocilizumab) CPR-SDAI was RUB 786867.9, CPR-CDAI – RUB 774285.7, and CPR-RAPID-3 – RUB 786867.9. In group 4 (tofacitinib) CPR-SDAI was RUB 1048831.2, CPR-CDAI – RUB 1088379.9, and CPR-RAPID – RUB 915730.8. Conclusion. CPR were lower with interleukin-6 inhibitor and Janus kinase inhibitor therapy than with B cell-depleting agent and TNF-α inhibitors therapy. Determination of CPR by SDAI, CDAI, and RAPID-3 indices revealed an advantage of interleukin-6 inhibitor therapy over Janus kinase inhibitor therapy.

Effectiveness of tacrolimus concomitant with biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis.

The study aimed to investigate the effectiveness and tolerance of biological disease-modifying antirheumatic drugs (bDMARDs) therapy administered concomitantly with tacrolimus (TAC) treatment in patients with rheumatoid arthritis. 2792 patients who underwent therapy with five bDMARDs (etanercept: ETN, adalimumab, golimumab, tocilizumab, and abatacept: ABT) were enrolled. Among the study subjects, 1582 were concomitant methotrexate (MTX group), 147 were concomitant TAC (TAC group), and 1063 were non-concomitant MTX and TAC (non-MTX/TAC group). The primary outcome was the incident rate of discontinuation of bDMARDs by adverse events (AEs) or loss of efficacy. Concerning the analysis for each reasons of discontinuation, including AEs and loss of efficacy, the hazards ratio (HR) was significantly lower in the TAC group than in non-MTX/TAC groups (AEs: HR = 0.39, 95% confidence interval, 0.23-0.68, loss of efficacy: HR = 0.49, 95% confidence interval, 0.30-0.78). The loss of efficacy with the use of ETN and ABT was lower in the TAC group than in non-MTX/TAC groups. Concomitant TAC did not induce elevated risk for discontinuation of AEs in all bDMARD analyses. Concomitant TAC with ABT or ETN showed higher retention rates than bDMARDs therapy without TAC or MTX. AEs did not increase over long-term observation.

Perioperative management of disease-modifying antirheumatic drugs for patients undergoing elective spine surgery: a systematic review.

In preparation for surgery, patients being treated with disease-modifying antirheumatic drugs (DMARDs) are recommended to either continue or withhold therapy perioperatively. Some of these drugs have known effects against bone healing, hence the importance of adequately managing them before and after surgery. We aim to assess the current evidence for managing conventional synthetic and/or biologic DMARDs in the perioperative period for elective spine surgery. A systematic review of four databases was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The included manuscripts were methodically scrutinized for quality, postoperative infections, wound healing characteristics, bone fusion rates, and clinical outcomes. Six studies were identified describing the management of conventional synthetic and/or biologic DMARDs. There were 294 DMARD-treated patients described undergoing various spine surgeries such as craniovertebral junction fusions. Three of the studies involved exclusive continuation of DMARDs in the perioperative window; one study involved exclusive discontinuation of DMARDs in the perioperative window; and two studies involved continuation or discontinuation of DMARDs perioperatively. Of patients that continued DMARDs in the perioperative period, 13/50 patients (26.0%) had postoperative surgical site infections or wound dehiscence, 2/19 patients (10.5%) had delayed wound healing, and 32/213 patients (15.0%) had secondary revision surgeries. A fusion rate of 14/19 (73.6%) was described in only one study for patients continuing DMARDs perioperatively. The available published data may suggest a higher risk of wound healing concerns and lower than average bone fusion, although this may be under-reported given the current state of the literature.