BACKGROUND: Clinical guidelines for the treatment of rheumatoid arthritis (RA) recommend reducing the use of glucocorticoids (GCs) due to the high risk of associated complications.
OBJECTIVE: To determine the frequency of GC cancellations and dose reductions in real clinical practice, while taking into account active RA therapy.
METHODS: The study group consisted of 303 patients with RA reliable according to ACR/EULAR criteria (women 79.9%, age 52.8±13.3, disease duration 9 [4; 16] years, DAS-28-CRP 4.9±1.0, RF seropositivity 77.4%, ACPA seropositivity 70.3%), who were prescribed or changed therapy with disease-modifying antirheumatic drugs (DMARDs), biologic disease-modifying antirheumatic drugs (bDMARDs) or Janus kinase inhibitors (iJAK) due to disease exacerbation and ineffectiveness of previous treatment. All patients initially received GC (7.7±3.8 mg/day equivalent of prednisolone). After adjustment of therapy, 42.9% of patients received methotrexate, 27.6% leflunomide, 2.5% sulfasalazine, hydroxychloroquine, or a combination with an Non-steroidal anti-inflammatory drugs, 63.7% bDMARDs, and 7.2% iJAK. The need for GC intake was assessed by a telephone survey conducted 6 months after the start of follow-up.
RESULTS: Telephone survey was possible in 274 (90.4%) persons. There was a significant decrease in pain intensity (numerical rating scale, NRS 0-10) from 6.3±1.4 to 4.3±2.4 (p<0.001), fatigue (NRS) from 6.7±2.3 to 5.2±2.1 (p<0.001), and functional impairment (NRS) from 5.4±2.1 to 3.9±2.0 (p<0.001). A positive PASS index (symptom status acceptable to patients) was noted in 139 (50.7%) patients. GC cancellation was noted in 19.7%, dose reduction in 25.9%, maintaining the same dose in 42.7%, and dose increase in 11.7%.
CONCLUSIONS: Against the background of intensive RA therapy, including combination of DMARDs with bDMARDs or iJAK, complete withdrawal or reduction of GC dose was achieved in less than half (45.6%) of patients after 6 months.
Обоснование. Актуальные клинические рекомендации по лечению ревматоидного артрита (РА) указывают на необходимость снижения использования глюкокортикоидов (ГК) в связи с высоким риском осложнений на фоне приема этих препаратов. Цель. Определить частоту отмен и снижения дозы ГК на фоне активной терапии РА в реальной клинической практике. Материалы и методы. Исследуемую группу составили 303 пациента с РА, достоверным по критериям ACR/EULAR (женщины – 79,9%, возраст – 52,8±13,3 года, длительность болезни – 9 [4; 16] лет, DAS-28-СРБ – 4,9±1,0, серопозитивность по ревматоидному фактору – 77,4%, по антителам к циклическому цитруллиновому пептиду – 70,3%), которым в связи с обострением заболевания и неэффективностью предшествующего лечения назначена или изменена терапия синтетическими базисными противовоспалительными препаратами (сБПВП), генно-инженерными биологическими препаратами (ГИБП) или ингибиторами янус-киназ (иJAK). Все пациенты исходно получали ГК (7,7±3,8 мг/сут в эквиваленте преднизолона). После коррекции терапии 42,9% пациентов получали метотрексат, 27,6% – лефлуномид, 29,5% – сульфасалазин, гидроксихлорохин или комбинацию сБПВП, 63,7% – ГИБП, 7,2% – иJAK. Оценивалась потребность в приеме ГК по данным телефонного опроса, проведенного через 6 мес после начала наблюдения. Результаты. Телефонный опрос удалось провести у 274 (90,4%) лиц. Отмечено достоверное снижение интенсивности боли (числовая рейтинговая шкала – ЧРШ 0–10) с 6,3±1,4 до 4,3±2,4 (p<0,001), усталости (ЧРШ) – с 6,7±2,3 до 5,2±2,1 (p<0,001), функциональных нарушений (ЧРШ) – с 5,4±2,1 до 3,9±2,0 (p<0,001). Положительный индекс PASS (состояние симптомов, приемлемое для пациентов) отмечен у 139 (50,7%) пациентов. Отмена ГК наблюдалась у 19,7%, снижение дозы – у 25,9%, сохранение прежней дозы – у 42,7%, повышение дозы – у 11,7%. Заключение. На фоне активной терапии РА, включающей комбинацию сБПВП с ГИБП или иJAK, через 6 мес удалось добиться полной отмены или снижения дозы ГК менее чем у 1/2 (45,6%) пациентов.

OBJECTIVE: This systematic review assessed the efficacy and safety of abatacept in patients with systemic juvenile idiopathic arthritis (JIA).
METHODS: Studies published between 2000 and 2021 were searched using PubMed, Embase, Cochrane, Ichushi-Web and clinical trial registries. The risk of bias was assessed according to the manual for development clinical practice guidelines by Minds, a project to promote evidence-based medicine in Japan.
RESULTS: Seven observational studies were included. American College of Rheumatology pediatric 30/50/70 responses at 3, 6 and 12 months were 64.8%/50.3%/27.9%, 85.7%/71.4%/42.9% and 80.0%/50.0%/40.0%, respectively. Outcomes on systemic symptoms, joint symptoms and activities of daily living were not obtained. No macrophage activation syndrome or infusion reaction occurred. Serious infection occurred in 2.6% of cases.
CONCLUSIONS: Abatacept improved the disease activity index. In addition, abatacept was as safe as interleukin-6 (IL -6) and IL-1 inhibitors. However, both the efficacy and safety data in this systematic review should be reviewed with caution because their quality of evidence is low or very low. Further studies are needed to confirm the efficacy and safety of abatacept for systemic JIA, especially its efficacy on joint symptoms.

OBJECTIVE: Osteoarticular infection (OAI) is a feared complication of Staphylococcus aureus bacteraemia (SAB) and is associated with poor outcomes. We aimed to explore risk of OAI and death following SAB in patients with and without rheumatoid arthritis (RA) and to identify risk factors for OAI in patients with RA.
METHODS: Danish nationwide cohort study of all patients with microbiologically verified first-time SAB between 2006-2018. We identified RA, SAB, comorbidities, and RA-related characteristics (e.g. orthopaedic implants, antirheumatic treatment) in national registries including the rheumatology registry DANBIO. We estimated cumulative incidence of OAI and death and adjusted hazard ratios (HRs, multivariate Cox regression).
RESULTS: We identified 18 274 patients with SAB (n = 367 with RA). The 90-day cumulative incidence of OAI was 23.1%(95%CI 18.8; 27.6) for patients with RA and 12.5%(12.1; 13.0) for patients without RA (non-RA) (HR 1.93(1.54; 2.41)). For RA patients with orthopaedic implants cumulative incidence was 29.4%(22.9; 36.2) (HR 1.75(1.08; 2.85), and for current users of tumor necrosis factor inhibitors (TNFi) it was 41.9%(27.0; 56.1) (HR 2.27(1.29; 3.98) compared with non-users). All-cause 90-day mortality following SAB was similar in RA (35.4%(30.6; 40.3)) and non-RA (33.9%(33.2; 34.5), HR 1.04(0.87; 1.24)).
CONCLUSIONS: Following SAB, almost one in four patients with RA contracted OAI corresponding to a doubled risk compared with non-RA. In RA, orthopaedic implants and current TNFi use were associated with approximately doubled OAI risk. One in three died within 90 days in both RA and non-RA. These findings encourage vigilance in RA patients with SAB to avoid treatment delay of OAI.

The aim of the study was to provide an overview of the practices of French general dentists (GDs) and specialists (SDs) concerning the management of patients with inflammatory bowel diseases (IBDs), rheumatic inflammatory diseases (IRDs), and vasculitis on biologic disease-modifying antirheumatic drugs (bDMARDs), conventional DMARDs, or immunosuppressants (ISs).
An online national cross-sectional survey with 53 questions was developed by a multidisciplinary team including rheumatologists, gastroenterologists and dentists based on their clinical experience. It was refined following a test with nine dentists in private practice and in hospital before being disseminated to the members of French scientific societies and colleges of dentistry teachers over 3 months. Responses of general dentists versus specialists were compared with respect to their experience in managing patients with IRDs or IBDs, knowledge/training, type of invasive procedure performed, management of medical treatment, perioperative oral-care protocols, and frequency of postoperative complications after invasive dental care procedures.
In total, 105 practitioners fully completed the survey (participation rate 11.1%). SDs more frequently performed invasive surgical procedures and were more aware of the recommendations of learned societies than GDs. They encountered more post-operative complications for patients on bDMARDs. For both SDs and GDs, most patients were managed without stopping treatment and pre- and postoperative antibiotics were prescribed to more than 75% of patients. When medical treatment was stopped, the decision was made by the prescribing physician.
Complications were reported more frequently by SDs when highly invasive procedures were performed on patients under active drug therapy. Certain common procedures, such as scaling and root planing, appear to be safe, regardless of treatment management. However, adapted guidelines for the practice of dentistry are needed to standardize the management of patients on bDMARDS, conventional DMARDs, or ISs.
French dentists perform a wide range of oral procedures on patients on bDMARDS, conventional DMARDs, or ISs under antibiotic coverage and antiseptic mouthwashes. SDs reported more postoperative complications after extensive invasive procedures for patients under active drug therapy, despite their greater knowledge of recommendations on how to manage such patients.

BACKGROUND: Biologic disease-modifying antirheumatic drugs (bDMARDs) have changed the treatment of juvenile idiopathic arthritis (JIA) patients notably, as bDMARDs enable substantially more patients to achieve remission. When sustained remission is achieved, tapering or even discontinuation of the bDMARD is advocated, to reduce side effects and costs. However, when and how to discontinue bDMARD therapy and what happens afterwards, is less known.
OBJECTIVE: With this scoping review we aim to collect available data in current literature on relapse rate, time to relapse (TTR) and possible flare associated variables (such as time spent in remission and method of discontinuation) after discontinuing bDMARDs in non-systemic JIA patients.
METHODS: We performed a literature search until July 2022 using the Pubmed database. All original studies reporting on bDMARD discontinuation in non-systemic JIA patients were eligible. Data on patient- and study characteristics, the applied discontinuation strategy, relapse rates and time to relapse were extracted in a standardized template.
RESULTS: Of the 680 records screened, 28 articles were included in this review with 456 non-systemic JIA patients who tapered and/or stopped bDMARD therapy. Relapse rate after discontinuation of bDMARDs, either abruptly or following tapering, were 40-48%, 36.8-45.0% and 60-78% at 6, 8 and 12 months respectively. Total relapse rate ranged from 26.3% to 100%, with mean time to relapse (TTR) of 2 to 8.4 months, median TTR 3 to 10 months. All studies stated a good response after restart of therapy after flare. JIA subtype, type of bDMARD, concomitant methotrexate use, treatment duration, tapering method, age, sex, and time in remission could not conclusively be related to relapse rate or TTR. However, some studies reported a positive correlation between flare and antinuclear antibodies positivity, younger age at disease onset, male sex, disease duration and delayed remission, which were not confirmed in other studies.
CONCLUSIONS: Flares seem to be common after bDMARD discontinuation, but little is known about which factors influence these flares in JIA patients. Follow up after discontinuation with careful registration of patient variables, information about tapering methods and flare rates are required to better guide tapering and/or stopping of bDMARDs in JIA patients in the future.

OBJECTIVE: This study aimed to assess the cost-effectiveness of biologic disease-modifying antirheumatic drugs (bDMARDs) for treating patients with psoriatic arthritis who failed conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).
METHODS: A decision tree and Markov model were constructed to capture long-term costs and outcomes from a societal perspective. Patients with psoriatic arthritis who failed 2 previous csDMARDs were modeled over a 3-month cycle with a lifetime horizon. Clinical probabilities were derived from a published meta-analysis. Prices of bDMARDs were proposed by pharmaceutical companies. Other costs and utilities were based on data in Thailand. All costs and outcomes were discounted at a 3% annual rate. Incremental cost-effectiveness ratio and a series of sensitivity analyses were performed.
RESULTS: All 11 bDMARDs (3 infliximab originator and biosimilars, 2 etanercept originator and biosimilar, golimumab, 2 secukinumab 150 mg and 300 mg, 3 adalimumab biosimilars) gained better quality-adjusted life-years (QALYs) with more costly than csDMARDs. Infliximab had the highest QALYs compared with other bDMARDs. Only secukinumab 150 mg showed the incremental cost-effectiveness ratio below the Thai threshold of 5152 US dollars per QALY. Cost of bDMARDs was the most influential factor.
CONCLUSIONS: At the current price, secukinumab 150 mg shows the value for money in the Thai context. Price negotiation is of great importance for other bDMARDs.

There is limited information regarding disease-modifying antirheumatic drug (DMARD)-dependent risks of overall, incident, and recurrent herpes zoster (HZ) during first-line biologic DMARD (bDMARD) or targeted synthetic DMARD (tsDMARD) treatment among patients with seropositive rheumatoid arthritis (RA) in terms of HZ risk.
A total of 11,720 patients with seropositive RA who were prescribed bDMARD or tofacitinib between January 2011 and January 2019 from the Korean Health Insurance Review & Assessment Service database were studied. A multivariate Cox proportional hazards regression model was adopted to evaluate the adjusted hazard ratio (aHR) with 95% confidence interval (CI) for the risk of HZ dependent on the choice of first-line bDMARDs or tsDMARD, including etanercept, infliximab, adalimumab, golimumab, tocilizumab, rituximab, tofacitinib, and abatacept.
During the 34,702 person-years of follow-up, 1686 cases (14.4%) of HZ were identified, including 1372 (11.7%) incident and 314 (2.7%) recurrent HZs. Compared with that of the abatacept group, tofacitinib increased the overall risk (aHR, 2.46; 95% CI, 1.61-3.76; P<0.001), incidence (aHR, 1.99; 95% CI, 1.18-3.37; P=0.011), and recurrence (aHR, 3.69; 95% CI, 1.77-7.69; P<0.001) of HZ. Infliximab (aHR, 1.36; 95% CI, 1.06-1.74; P=0.017) and adalimumab (aHR, 1.29; 95% CI, 1.02-1.64; P=0.032) also increased the overall HZ risk. Moreover, a history of HZ was found to be an independent risk factor for HZ (aHR, 1.54; 95% CI, 1.33-1.78; P<0.001).
HZ risk is significantly increased in RA patients with a history of HZ after the initiation of bDMARDs or tsDMARD. The risk of incident and recurrent HZ was higher after tofacitinib treatment in patients with RA than that after treatment with bDMARDs. Individualized characteristics and history of HZ should be considered when selecting bDMARDs or tsDMARD for RA patients considering HZ risks.

BACKGROUND: To 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.
METHODS: The 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.
CONCLUSIONS: Our 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.
BACKGROUND: Chinese Clinical Trial Registry ChiCTR2100044751. Registered on 26 March 2021.

The aim of this study was to analyze the therapeutic results of rheumatoid arthritis (RA) therapy with different biologic disease-modifying antirheumatic drugs (bDMARDs) and the first Janus-activated kinase (JAK) inhibitor in real-life clinical settings. This is a prospective, observational, longitudinal study at the largest rheumatology clinic in Bulgaria conducted during the period 2012-2020. One hundred seventy-four patients were followed up for a period of one year. Patients naïve to biological therapy were consecutively assigned on the available at the time bDMARDs (infliximab, etanercept, adalimumab, rituximab, golimumab, cetrolizumab, tocilizumab) or tofacitinib. We evaluated the disease activity score (DAS28-CRP), Health assessment questionnaires (HAQ) and short form 36 (SF-36) were applied at the initiation of biological therapy, after 6, and 12 months of follow-up. We analyze the changes in the two major subgroups of SF36-physical (MCS) and mental health (PCS). The age and gender distribution were similar between the groups on bDMARDs and tsDMARD. All observed indicators for disease control and QoL improve after the initiation of the biological or JAK inhibitor therapy. We also analyze the effect of therapies on DAS28-CRP, HAQ, SF-36 (PCS, MCS). Dispersion analysis for the effect of therapy measured through DAS28 between 1st and 3rd measurement shows a statically significant difference in between the average effect of therapies (p = 0.005). According to the average change in DAS28 between the first and third measurement the most effective is the golimumab (Median difference = 2.745), followed by rituximab (median = 2.305) and etanercept (median = 2.070). According to the average change in HAQ between first and third the most effective is tofacitinib (median 0.563), followed rituximab and infliximab (median 0.500 for both). Less effective in term of HAQ changes between the first and third measurement appears to be etanercept (median difference 0.250). All differences are statistically significant (p < 0.05). Regarding the changes in the QoL measured with SF-36 MCS and PCS there is no statistically significant differences in the average effect of different therapeutic agents. Tofacitinib is non-inferior in comparison to bDMARDs and improve both-disease activity and QoL in patients with RA.

BACKGROUND: Diagnosis difficulties are common for ankylosing spondylitis (AS) patients, leading to inadequate and inconsistent treatment. We evaluated the national and geographic variability in disease diagnosis and treatment in the United States.
METHODS: This retrospective, cross-sectional analysis utilized the IBM® MarketScan® Administrative Claims Database from 2014 to 2019. AS patients ≥ 18 years of age with continuous medical and pharmacy enrollment during the calendar year and complete geographic information during the study period were included. Patient cohorts assessed were D1 (≥ 1 AS diagnoses within each calendar year of assessment between 2014 and 2019), D2 (≥ 2 non-rheumatologist AS diagnoses), and D3 (≥ 2 rheumatologist AS diagnoses). For D2 and D3, diagnoses were ≥ 6 months apart, but within 18 months. Annual AS diagnostic prevalence and treatment rates were determined from 2014 to 2019 nationally and per state in 2019. Treatments assessed were disease-modifying antirheumatic drugs (DMARDs), opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and methotrexate.
RESULTS: Nationally, AS diagnostic prevalence increased from 2014 to 2019, with 2019 rates of 9.6 (D1), 5.1 (D2), and 3.5 (D3) per 10,000 persons. Diagnostic prevalence varied between states, which was not explained by age, sex, racial distribution, or rheumatologists per capita. Nationally, a greater percentage of D3 patients vs. D1 and D2 patients received biologic/targeted synthetic DMARDs (bDMARD/tsDMARDs) and conventional synthetic DMARD. Opioid use ranged from 37 to 40% in 2019 and decreased from 2014 for all cohorts. Corticosteroid and methotrexate use decreased slightly, while NSAID and bDMARD/tsDMARD use generally increased from 2014 to 2019.
CONCLUSIONS: AS diagnostic prevalence is increasing nationally, though it remains low among some states. bDMARD/tsDMARDs use was more common among patients treated by rheumatologists. Opioid and corticosteroid use is decreasing, though national rates remain high with significant state variability. Further education is needed, particularly in states with low prevalence and inadequate treatment, to improve diagnosis and treatment.