Antirheumatic Research Articles

Increased adoption of IL-1 pathway inhibition and the steroid-sparing paradigm shift: temporal trends in recurrent pericarditis treatment from the RESONANCE patient registry

Abstract Background Recurrent pericarditis (RP) is a chronic autoinflammatory disease mediated by IL-1 that requires long-term treatment. While the 2015 European Society of Cardiology Guidelines position IL-1 pathway inhibition only after corticosteroids, complications associated with long-term steroid use underscore the importance of steroid-sparing strategies. Rilonacept, an IL-1α and IL-1β cytokine trap, is the only FDA-approved treatment for RP (available since April 2021). RESONANCE, an ongoing 5-year non-interventional US registry of patients (pts) with RP, has collected real-world data from pts cared for by cardiologists with a focus on pericardial disease, with a goal of informing contemporary RP clinical management. Purpose Analysis of temporal trends in RP management from RESONANCE. Methods From a database cut-off (DCO) on 21 December 2023, patient demographics and disease characteristics are reported for 242 active RP pts (excluding RHAPSODY prior participants) at 20 US sites (median [Q1:Q3] 2.1 [1.5:2.6] years and 556 patient-years [PY] of observation). Complete medication class use data were available for 239 pts (total 546 PY). Proportional medication class use prior to initiating rilonacept was analyzed annually across the observation period. Results Mean (standard deviation) age at DCO was 50.2 (16.6) years; 58.1% were female. Median [Q1:Q3] disease duration at DCO from index pericarditis episode was 3.1 [2.2:5] years. Median [Q1:Q3] number of prior recurrences at enrollment was 3 [2:5]. Prior to rilonacept availability, NSAIDs/Colchicine/Aspirin represented the highest proportion of treatment (73% of PY); steroid use was 9% of PY, IL-1 pathway inhibition (anakinra) was 13% of PY, and conventional synthetic disease modifying antirheumatic drugs (csDMARDs) were 0.46% PY (no RP-specific treatment was 5% of PY) (Fig 1). In the years since rilonacept availability, proportional IL-1 pathway inhibition use has increased, from 13% of PY in 2020-21 to 26% of PY in 2023, driven by an increase in rilonacept use (6%, 13%, 16% of PY in 2021, 2022, and 2023, respectively). Over that same period, proportional NSAIDs/Colchicine/Aspirin use (57%-63% of PY) has been consistently 6-times more than proportional steroid use (10%-11% of PY). Among pts who initiated rilonacept (n=81), similar proportions transitioned from NSAIDs/Colchicine/Aspirin as from corticosteroids (Fig 2), a robust trend observed each year. Of those pts transitioning from corticosteroids, 1/3 had used corticosteroids for <30 days and 1/3 for >6 months. Conclusions Real-world data from the RESONANCE registry reveal a temporal shift in RP management in US centers with RP-focused cardiologists, with increased proportional IL-1 pathway inhibition use since rilonacept availability in 2021. Advancing beyond 2015 guideline recommendations, IL-1 pathway inhibition is often being used as steroid-sparing treatment, i.e., after colchicine instead of chronic corticosteroids.

Escalation to Biologics After Methotrexate Among US Veterans with Rheumatoid Arthritis Grouped by Rural Versus Urban Areas.

Racial and ethnic disparities in rheumatoid arthritis (RA) outcomes are well recognized. However, whether disparities in RA treatment selection and outcomes differ by urban versus rural residence, independent of race, have not been studied. Our objective was to evaluate whether biologic disease modifying anti-rheumatic drugs (bDMARD) initiation after methotrexate use differs by rural versus urban residence among Veterans with RA. In this retrospective cohort study utilizing national U.S. Veterans Affairs databases, we identified adult patients with RA based on presence of diagnostic codes and DMARD use. We included patients receiving an initial prescription of methotrexate (index date) between 2005 and 2014, with data through 2016 used for follow-up. Urban-rural status was categorized using the Veteran Health Administration's Urban/Rural classification. Our primary outcome of interest was time to biologic initiation within two years of starting methotrexate. Multivariable Cox proportional hazards models were conducted adjusting for demographics, comorbidities, and rheumatoid factor or anti-CCP positivity. Among 17,395 veterans with RA (88% male, 42% with rural residence) fulfilling eligibility criteria, 3,259 (19%) initiated a biologic within the first two years of follow up. In multivariable models, residence in an urban area was associated with a statistically significant higher biologic use compared to rural areas (adjusted hazard ratio (aHR) 1.10, 95% CI 1.02-1.18). Our study found only modest differences in initiation of biologic therapies among rural versus urban residing Veterans with RA in the VA healthcare system. These findings suggest that disparities are not easily explained by rurality within the VA healthcare system.

Factors predicting treatment response to biological and targeted synthetic disease-modifying antirheumatic drugs in psoriatic arthritis - a systematic review and meta-analysis.

The therapeutic response of patients with psoriatic arthritis (PsA) varies greatly and is often unsatisfactory. Accordingly, it is essential to individualise treatment selection to minimise long-term complications. This study aimed to identify factors that might predict treatment response to biological and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs) in patients with PsA and to outline their potential application using artificial intelligence (AI). Five electronic databases were screened to identify relevant studies. A random-effects meta-analysis was performed for factors that were investigated in at least four studies. Finally, 37 studies with a total of 17,042 patients were included. The most frequently investigated predictors in these studies were sex, age, C-reactive protein (CRP), the Health Assessment Questionnaire (HAQ), BMI, and disease duration. The meta-analysis revealed that male sex (odds ratio (OR) = 2.188, 95% confidence interval (CI) = 1.912-2.503) and higher baseline CRP (1.537, 1.111-2.125) were associated with greater treatment response. Older age (0.982, 0.975-0.99), higher baseline HAQ score (0.483, 0.336-0.696), higher baseline DAPSA score (0.789, 0.663-0.938), and higher baseline tender joint count (TJC) (0.97, 0.945-0.996) were negatively correlated with the response to therapy. The other factors were not statistically significant but might be of clinical importance in the context of a complex AI test battery. Further studies are needed to validate these findings and identify novel factors that could guide personalised treatment decisions for PsA patients, in particular in developing AI applications. In accordance with the latest medical developments, decision-support tools based on supervised learning algorithms have been proposed as a clinical application of these predictors. Key messages • Given the often unsatisfactory and unpredictable therapeutic response in patients with Psoriatic Arthritis (PsA), treatment selection must be highly individualized. • A systematic literature review was conducted to identify the most reliable predictors of treatment response to biologic and targeted synthetic disease-modifying antirheumatic drugs in PsA patients. • The potential integration of these predictors into AI tools for routine clinical practice is discussed.

The safety and feasibility of colchicine uptitration in the management of idiopathic recurrent pericarditis

Abstract Introduction Colchicine is recommended first line in the management of idiopathic recurrent pericarditis (IRP) at low doses (0.5 - 1 mg/24h). In cases refractory to low dose colchicine, corticosteroid use is common, despite an increased risk of disease recurrence and the risk of complications resulting from corticosteroid dependence. Biologic agents that block interleukin-1, anakinra and rilonacept, are highly effective in IRP, but their use is limited by expertise and cost. Colchicine uptitration is recommended by consensus international guidance in familial Mediterranean fever, a disease characterised by recurrent serositis, and, hence, offers an accessible steroid sparing approach to the management of treatment-refractory idiopathic recurrent pericarditis Purpose To explore the safety and feasibility of colchicine uptitration in patients with IRP refractory to low dose colchicine (0.5-1 mg/24h). Methods Retrospective review of electronic medical records of all patients with IRP and familial Mediterranean fever reviewed at a tertiary centre 2013-2023. Treatment-refractory IRP cases were defined as active disease despite colchicine 1mg/24h or disease requiring other prophylactic drugs, and corticosteroid dependence as daily corticosteroid use for 6 months. Results Of 121 IRP cases, 77 (63.6%) were treatment refractory at first review. Median follow up was 24 months (IQR 6 – 36). Corticosteroid dependence complicated 34/77 (44.2%) cases. Of treatment-refractory cases without corticosteroid dependence, 42/43 (97.7%) were treated with colchicine uptitration and 4/43 (9.3%) with anti-interleukin-1 biologic(s); none became corticosteroid dependent. Of corticosteroid dependent cases, 30/34 (88.2%) were treated with colchicine uptitration and 13/34 (38.2%) with anti-interleukin-1 biologic(s). Corticosteroids were fully discontinued in 25/34 (73.5%): 8/25 (32.0%) weaned with colchicine uptitration alone, 14/25 (56.0%) with anti-interleukin-1 biologic(s) and 3/21 (14.3%) with azathioprine. Median corticosteroid duration was 17.5 months (IQR 13 - 44.25) and corticosteroid toxicity occurred in 8/34 (23.5%). Among the 76/77 cases (98.7%) treated with colchicine (median maintenance dose 2 mg/24h (IQR 1.5-2)), permanent discontinuation was uncommon (3/76, 3.9%) and due to gastrointestinal symptoms. Self-limiting liver transaminase elevation was common (29/76, 38.2%) but did not lead to discontinuation in any case. The prevalence of liver transaminase elevation among patients with familial Mediterranean fever on life long colchicine was 181/568 (31.9%). Conclusions In this treatment-refractory pericarditis cohort, colchicine uptitration enabled avoidance of new corticosteroid dependence, facilitated corticosteroid discontinuation and was well tolerated. This contrasts with the frequent toxicity seen with prolonged corticosteroid use and offers an accessible steroid sparing approach to IRP management that warrants prospective investigation.

A case of rapidly progressive hair loss due to azathioprine, and the prevalence of NUDT15 variants among Japanese patients with autoimmune blistering diseases: A single-center retrospective observational study.

Autoimmune blistering diseases (AIBDs), classified into pemphigus and pemphigoid, consist of relatively rare skin disorders caused by autoantibodies that target desmosomal and hemidesmosomal proteins, respectively. Although systemic corticosteroids are used as a first-line treatment for AIBDs, azathioprine is frequently co-administered as a steroid-sparing agent. Azathioprine is metabolized into thioguanine nucleotides (TGNs) which are its major active metabolites. The enzyme nudix hydrolase 15 (NUDT15) plays a key role in regulating TGNs. Serious side effects of azathioprine, including leukopenia and alopecia, are known to be particularly problematic in individuals with NUDT15 variants. The single-nucleotide polymorphism c.415C >T (p.Arg139Cys) is one of the most frequent NUDT15 variants associated with severe thiopurine toxicity. Recently, we treated a case of pemphigus vulgaris in a patient with NUDT15 variants in which the patient developed rapidly progressive diffuse hair loss and myelosuppression while receiving azathioprine. Previous reports on NUDT15 polymorphisms mainly focused on patients with inflammatory bowel disease or hematological malignancies, and the prevalence of NUDT15 polymorphisms remains unknown in AIBDs. This highlights the urgent need for research on NUDT15 polymorphisms in AIBDs to achieve a better understanding of the genetic factors influencing adverse reactions to azathioprine. To clarify the prevalence of NUDT15 variants in Japanese patients with AIBDs, we retrospectively reviewed the medical records of 78 patients with AIBDs (26 with bullous pemphigoid, 26 with pemphigus vulgaris, 17 with pemphigus foliaceus, and nine with other AIBDs) who had come to Hokkaido University Hospital between 2018 and 2023. The frequencies of NUDT15 variants of Arg/Arg, Arg/Cys, and Cys/Cys in these patients were approximately 72%, 23%, and 5%, respectively. Our findings indicate a prevalence of NUDT15 variants in AIBD patients that is similar to the prevalences of previous studies on patients with other diseases. These results emphasize the importance of screening for NUDT15 variants prior to initiating azathioprine treatment in Japanese patients with AIBDs.

Management of human epidermal growth factor receptor inhibitors-related acneiform rash: A position paper based on the first Europe/USA Delphi consensus process.

There is a need for unified guidance in the management of acneiform rash induced by epidermal growth factor receptor inhibitors (EGFRi) among dermatologists. To establish unified international guidelines for the management of acneiform rash caused by EGFR inhibitors, based on an experts' Delphi consensus. The initiative was led by five members of the European Academy of Dermatology and Venereology Task Force 'Dermatology for Cancer Patients' who developed a questionnaire that was circulated to a group of 32 supportive oncodermatology experts in Europe, Canada, Argentina, the US States and Asia. The questionnaire consisted of 84 statements in total, regarding diagnosis and treatment of EGFRi-induced acneiform rash. Experts responded to an anonymous 5-point Likert scale survey. The coordinators collected the first-round responses that were checked for consensus (≥75% agreement in positive [agree or strongly agree] or in negative [disagree or strongly disagree] vote). The statements that did not reach strong consensus in the first round were revised, according to experts' feedback, for a second-round survey. Strong consensus was reached in 75/84 (89.3%) of the statements, whilst moderate consensus was achieved in 6/84 elements. Key points include consideration of low-dose isotretinoin for refractory grade II/III acneiform rash, use of topical steroid-sparing agents like topical pimecrolimus in the maintenance phase and use of doxycycline in either 100 or 200 mg per day as prophylactic treatment. Interestingly, experts did not recommend topical antibiotics, neither for prevention, nor for treatment. Consensus failure in 3/84 objects is mostly related to the lack of robust data on these topics. This consensus offers crucial insights often overlooked by radiotherapists, general practitioners, dermatologists and oncologists, and it is expected to improve the management of oncologic patients treated with EGFRi in different settings and continents.

Effectiveness of JAK Inhibitors Compared With Biologic Disease-Modifying Antirheumatic Drugs on Pain Reduction in Rheumatoid Arthritis: Results From a Nationwide Swedish Cohort Study.

To compare the effectiveness of JAK inhibitors (JAKis) and biologic disease-modifying antirheumatic drugs (bDMARDs) on pain in patients with rheumatoid arthritis. In this retrospective study, we investigated patients with a diagnosis of rheumatoid arthritis, starting treatment with a JAKi (n = 1,827), a tumor necrosis factor inhibitor (TNFi; n = 6,422), an interleukin-6 inhibitor (n = 887), abatacept (n = 1,102), or rituximab (n = 1,149) in 2017 to 2019, using data from several linked Swedish national registers. Differences in change in pain, assessed with a visual analogue scale (0-100 mm), from baseline to 3 months, as well as proportions of patients remaining on initial treatment with low pain (visual analogue scale pain <20) at 12 months, were compared between treatments. Comparisons of treatment responses between JAKis and bDMARDs were evaluated using multivariable linear regression, adjusted for patient characteristics, comorbidities, current comedication, and previous treatment. JAKi treatment was associated with a greater decrease in pain at 3 months compared with TNFi treatment (adjusted mean additional decrease 4.0 mm; 95% confidence interval 1.6-6.3), with similar trends in comparisons with non-TNFi bDMARDs. More patients achieved low pain at 12 months on JAKis compared with TNFis, in particular among those previously treated with at least two bDMARDs (adjusted change contrast 5.3 percentage points; 95% confidence interval 1.0-9.6). JAKis had a slightly better effect on pain outcomes at 3 and 12 months compared with TNFis, with significantly greater differences in patients previously treated with at least two bDMARDs. The effect of JAKis on pain reduction was at least similar to that of non-TNFi bDMARDs.

Therapeutic potential of d-limonene in rheumatoid arthritis: Modulation of inflammatory, anti-inflammatory cytokines, and prostaglandin E2.

Rheumatoid arthritis (RA) is a persistent autoimmune disorder predominantly affecting the joint structures, eliciting inflammatory responses, and ultimately leading to degenerative changes without proper medical intervention. Ultimately, this can severely impair joint function and impact the patient's quality of life. Current treatment approaches include disease-modifying anti-rheumatic drugs, non-steroidal anti-inflammatory drug, corticosteroids, and biologic therapies for RA management. The current study contributes to the ongoing advancements in RA treatment. d-Limonene is a monocyclic monoterpene. It is present in essential oils of various aromatic plants, such as Lippia alba and Artemisia dracunculus, and in citrus fruits such as lemon and orange. It has reported anti-inflammatory and anti-nociceptive properties and was selected for the current study as a potential anti-arthritic candidate. It was administered at three dosages (25, 50, 100 mg/kg, b.w., p.o) in Complete Freund's adjuvant-induced arthritic rats over 28 days. The efficacy of the compound was compared to piroxicam, a widely used standard drug for treating RA. The anti-arthritic activity of the compound was assessed by measuring arthritic scoring and plethysmometry at both baseline and post-intervention stages. Additional confirmation of the investigation was sought by performing biochemical and hematological activities. Moreover, quantitative polymerase chain reaction was employed to determine the levels of messenger RNA expression for transcription factors such as tumor necrosis factor-α, interleukin (IL)-1β, nuclear factor-κB, matrix metalloproteinase-3, IL-6, and IL-4 in the blood. The levels of PGE2 were evaluated by enzyme-linked immunosorbent assay. The histopathological and radiographic studies were also carried out for further confirmation. The results of these findings supported our assertion regarding the anti-arthritic potential of the compound.

Orbital Myositis and Strabismus: Clinical Profile, Management, and Predictive Factors for Recurrence.

To study the clinical profile of patients with orbital myositis and their management modalities and predictive factors for recurrence. The records of all consecutive patients diagnosed as having orbital myositis from 2010 to 2022 were reviewed. Patient demographics, presenting complaints, visual function, primary gaze deviation, and extraocular muscle involved were studied in the clinical profile. The radiological modalities and their management along with the recovery status and need for surgical intervention were documented. Fifty-two patients (55 eyes) (69% women) were diagnosed as having orbital myositis with a mean age of 36 ± 16 years presenting with periocular pain (55%) followed by diplopia (49%). Disease was unilateral in 94%. Sixty percent had ocular misalignment in primary gaze. The medial rectus was the most involved muscle (58%), with abduction limitation in 73%. Computed tomography (42%), magnetic resonance imaging (42%), and combined imaging (16%) were used in localizing the disease. Muscle biopsy was done in 38% of patients. Systemic immunomodulators were required in 16%. Strabismus surgery was planned in 15% of patients and done in 11%. Recurrence was noted in 43%. Abrupt cessation of steroids was a significant risk factor in recurrence of the disease (P = .046). Recovery was partial in 44% of patients and complete in 47%. Systemic steroids with slow taper has satisfactory outcomes in orbital myositis. Patients refractory to treatment ideally should undergo biopsy and begin taking steroid-sparing agents. Once the disease is in remission, residual disease can be surgically treated for better functional outcome. [J Pediatr Ophthalmol Strabismus. 20XX;X(X):XXX-XXX.].

Cost variation analysis of disease modifying anti rheumatic drugs in Indian market

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease with systemic complications, necessitating treatment to manage inflammation and prevent joint damage. In India, significant cost discrepancies exist among branded formulations of generic drugs, posing a financial burden on patients and impacting treatment adherence. This study focuses on cost differences of disease modifying anti rheumatic drugs (DMARDs) among Indian brands and advocating strict adherence to drug price control order (DPCO) rules and suggests scheduling non-scheduled drugs under DPCO. Methods: This observational study analysed the cost of 6 oral DMARDs across 16 tablet formulations using data from National Pharmaceutical Pricing Authority (NPPA) and DPCO ceiling prices 2024. Number of brands per formulation, cost ratios, percentage variations, and DPCO price violations was analysed. Statistical analysis was performed using Microsoft Excel Office 2021, and Zotero was utilized for managing references. Results: This study highlights significant price variations among DMARDs in the Indian market, with methotrexate 2.5mg exhibiting the highest cost ratio (1:3.63) and percentage cost variation (263.6%). Azathioprine 50mg has the most brands available (23), while sulfasalazine 500mg, sulfasalazine 1000mg, and tofacitinib 11mg are among the formulations with the fewest brands (3 each). Notably, sulfasalazine 500mg and hydroxychloroquine 200mg showed the most frequent instances of pricing violations above DPCO recommendations. Conclusions: Strict regulation for price control and monitoring should be implemented since the DPCO has not yet achieved its goal of enforcing price ceilings, and non-scheduled drugs should be included under DPCO regulations effectively to enhance adherence to RA therapy.

Difficult-to-treat Takayasu arteritis: a case-based review.

Takayasu arteritis is a rare chronic inflammatory large vessel vasculitis which affects the aorta and its large branches. The diagnosis is based on the 2022 ACR/EULAR classification criteria for Takayasu arteritis. The management of this vasculitis is challenging. Although it is corticosteroid-responsive, relapses and disease progression are common. Thus, it is possible to resort to alternative conventional synthetic disease-modifying anti-rheumatic drugs and biologics, as second-line such as tumor necrosis factor-alpha inhibitors, tocilizumab, or JAK inhibitors as second-line agents is possible. Nevertheless, in some complex cases, the vasculitis remains active despite different proposed therapeutic lines, and a multitarget approach could induce sustained remission. We report herewith a case of 33-female patient with a refractory Takayasu arteritis which remained active after three different therapeutic lines with tocilizumab, then infliximab, then Upadacitinib. Finally, we consider a successful multitarget approach with a combination of infliximab, Upadacitinib, and methotrexate.

Improvement in spinal pain at night and its impact on long-term outcomes in radiographic axial spondyloarthritis: Results from Ixekizumab COAST-V randomised trial

IntroductionSpinal pain at night is a major contributor to the patient burden of radiographic axial spondyloarthritis (r-axSpA), resulting in substantial functional limitations and impairment of health-related quality of life (QoL). Ixekizumab (IXE), an interleukin-17A inhibitor, has shown efficacy in patients with r-axSpA. ObjectiveTo assess spinal pain at night improvement up to week (W) 52 in COAST-V and to determine if clinically important improvement in spinal pain at night at W16 is associated with improvement in disease activity and other patient-reported outcomes (PROs) at W16 and W52. MethodsThe 52 W phase 3 COAST-V trial investigated the efficacy of IXE in patients with r-axSpA that were naïve to biological disease-modifying anti-rheumatic drug (bDMARD). Patients were randomised to IXE every two weeks (Q2W), IXE every four weeks (Q4W), adalimumab (ADA) Q2W, or placebo up to W16. Patients were categorised as achieving or not achieving a ≥3-point improvement, considered a clinically important improvement (CII), in spinal pain at night at W16. Associations between achieving CII in spinal pain at night at W16 and change from baseline in disease activity (ASDAS, ASAS40), Fatigue severity NRS, JSEQ, WPAI and the SF-36 survey, were tested using analysis of covariance (continuous variables) and logistic regression (binary variables). ResultsAt W16, 63.0 % (n=51), 46.7 % (n=42), and 32.2 % (n=28) of patients treated with IXE Q4W, ADA Q2W, and placebo, respectively, had reached a CII in spinal pain at night. Of those who were treated with IXE Q4W and achieved a CII in spinal pain at night at W16, 58.8 % and 66.7 % achieved an ASDAS <2.1 at W16 and W52 while 25.5 % and 29.4 % of patients also achieved ASDAS <1.3 at W16 and W52, respectively. Results at W16 and W52 show an improvement in disease activity, functioning, and health related QoL for patients who achieved a CII in spinal pain at night at W16. ConclusionA larger proportion of patients treated with IXE Q4W achieved rapid and clinically meaningful improvement in spinal pain at night versus placebo, with improvements maintained up to W52. Achieving a CII in spinal pain at night at W16 was associated with improved disease activity, functioning, PROs, and QoL at W16 and W52. Trial registrationClinicalTrials.gov NCT02696785

Analysis of methotrexate use practice in patients with rheumatoid arthritis and psoriatic arthritis

Background. Pharmacoepidemiological studies play a key role in optimizing pharmacotherapy for various diseases. In particular, significant progress in the treatment of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) necessitates a detailed analysis of the consumption of disease-modifying antirheumatic drugs. The modern therapeutic concept for these conditions focuses on achieving and maintaining long-term remission, which positions methotrexate (MTX) as a first-line agent, characterized by high effectiveness, safety and advantageous pharmacoeconomic profiles.Objective: to investigate the characteristics of MTX use in real clinical practice among patients with RA and PsA during outpatient medical care.Material and methods. The study comprised two parts: a retrospective cross-sectional analysis of MTX consumption dynamics in 2018, 2020, and 2023 via ATC/DDD (Anatomical Therapeutic Chemical classification, ATC; defined daily dose, DDD) methodology, and a longitudinal non-interventional pharmacoepidemiological study conducted in 2023 using the medical information system “BARS. Healthcare”.Results. The ATC/DDD analysis demonstrated a significant increase in MTX consumption among patients with RA and PsA: from 302,428.6 to 319,114.3 DDDs per 1,000 patients per year for RA, and from 28,157.1 to 310,771.6 DDDs per 1,000 patients per year for PsA in 2018 and 2023, respectively. The most frequently prescribed dose of MT was 15 mg/week. The primary therapeutic combination for 55.8% of patients was “MT + nonsteroidal anti-inflammatory drugs”, with 32.7% of patients also receiving glucocorticoids (GCs) as part of this combination. The study identified a high frequency of prescriptions for proton pump inhibitors, GCs, and cholecalciferol, highlighting the activity of diseases under consideration, potential complications, and the necessity for the prevention of clinically significant drug interactions.Conclusions. The conducted study confirmed that MTX remains the main drug for the treatment of RA and PsA. The ATC/DDD analysis demonstrated a significant increase in MTX consumption in recent years, correlating with its therapeutic effectiveness and accessibility. The high frequency of concomitant prescriptions underscores the complexity of treating RA and PsA and the need for an interdisciplinary approach to ensure safety and efficacy of the therapy.

Incidence of serious respiratory tract infections and associated characteristics in a population exposed to immunosuppressive therapies: a register-based population study

BackgroundImmunosuppressive therapies are associated with a risk of infections. Nevertheless, their incidence in this population remains unclear. This study aims to determine the incidence of serious respiratory tract infections (SRI) in a population exposed to immunosuppressive therapies.MethodsData from a representative sample of the French healthcare claims from 01/01/2014 to 12/31/2019 were analyzed. Exposure to immunosuppressive therapy was defined by the dispensation of drugs through community pharmacies or in hospitals. SRI diagnosis was based on ICD-10 codes from hospitalization records. A cohort analysis was performed to estimate standardized SRI incidence rates. A nested case-control analysis within this cohort was used to study the characteristics associated with SRI.ResultsWe identified 24,122 individuals exposed to immunosuppressive therapies, among which 1,559 developed SRI, resulting in a standardized incidence rate of 1,398 per 100,000 person-years. In this population, the risk of SRI was associated with a history of cancer (OR 2.68, 95% Confidence Intervals (CI) 2.24–3.21; p < 0.001), chronic respiratory disease (2.62, 95%CI 2.17–3.16; p < 0.001), end-stage renal failure (2.38, 95%CI 1.37–4.13; p = 0.003), neurodegenerative diseases (1.52, 95%CI 1.07–2.17; p = 0.026), diabetes (1.44, 95%CI 1.14–1.82; p < 0.001), psychiatric diseases (1.27, 95%CI 1.06–1.52; p < 0.001), and cardiovascular diseases (1.26, 95%CI 1.04–1.52; p = 0.002). Compared to corticosteroids alone, the risk of SRI was lower in individuals treated with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD) only (0.44, 95%CI 0.25–0.78; p < 0.001).ConclusionIn the population exposed to immunosuppressive therapies, a history of chronic disease is associated with an increased risk of SRI. This risk is lower in those receiving csDMARD alone than corticosteroids alone.

Efficacy of the cardiac glycoside digoxin as an adjunct to csDMARDs in rheumatoid arthritis patients: a randomized, double-blind, placebo-controlled trial.

Inflammation and angiogenesis are two main mechanisms that act as mutual pathways in rheumatoid arthritis (RA). This work aimed to study the efficacy of digoxin as an adjunct therapy to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) in active RA patients. In a randomized, double-blinded, placebo-controlled study, 60 adult patients with active RA received a placebo or digoxin (0.25mg every other day) combined with csDMARDs for 6months. The American College of Rheumatology (ACR) 20, ACR50, and ACR70 response rates and the disease activity score (DAS28) were assessed for patients. Flow cytometric analysis of Th17 cells and serum concentrations of IL-17A, IL-23, HIF-1α, and VEGF were evaluated before and after three and 6months of therapy. Following three and 6months of digoxin therapy combined with csDMARDs, significant differences were detected in laboratory and clinical parameters relative to the control group. After 6months, 83.3% of patients in the digoxin group, compared to 56.7% in the control group, achieved an ACR20 response (p = 0.024). The digoxin group had a significantly higher percentage of patients who achieved DAS28 remission after 6months (p = 0.024). Notable improvements in the Health Assessment Questionnaire Disability Index, ACR50, and ACR70 were detected in the digoxin group. Digoxin was well tolerated and exerted profound immunomodulatory and anti-inflammatory effects in RA patients, and may also exhibit anti-angiogenic properties, indicating that it might be an effective adjunct to csDMARDs in treating RA. clinicaltrials.gov, identifier NCT04834557.

Switching from interleukin-6 receptor inhibitors to the direct interleukin-6 inhibitor olokizumab in patients with rheumatoid arthritis: efficacy and safety during one year of therapy

Objective: to investigate the efficacy and safety of olokizumab (OKZ) in patients with rheumatoid arthritis (RA) over a 12-month period after switching from interleukin (IL)-6 receptor inhibitors (iIL6R) for non-medical reasons.Material and methods. A retrospective cohort study conducted in 11 centers in the Russian Federation included 110 patients with confirmed diagnosis of RA according to 2010 ACR/EULAR criteria. In all patients in early 2022 (due to problems with drug supply during the coronavirus pandemic) iIL6R were switched for non-medical reasons to OKZ at a dose of 64 mg once every 2 weeks or once every 4 weeks in accordance with the instructions for the medical use of OKZ.Data on clinical efficacy, safety and changes in the dosing regimen of the drugs over an observation period of one year are presented. We assessed the dynamics of the clinical indicators: number of painful and swollen joints, pain on a visual analogue scale and DAS28-ESR/CRP indices. Routine laboratory tests included assessment of red and white blood cells count, ESR, hemoglobin, CRP, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin and cholesterol. Adverse events (AEs) were recorded in accordance with standard practice.Results and discussion. After 6 months of therapy, the proportion of patients who achieved remission/low disease activity according to DAS28-ESR and DAS28-CRP decreased to 70.1% and 72.9%, respectively, and the proportion of patients with moderate and high activity according to DAS28-ESR increased to 26.1% and 3.7%, respectively, and according to DAS28-CRP to 21.5% and 5.6 %, respectively. After 12 months, remission/low disease activity according to DAS28-ESR and DAS28-CRP was achieved in 81.4% and 83.5% of patients, respectively, and 18.6% and 16.5% of patients had moderate activity.In the OKZ monotherapy group, after 6 months of treatment 22 (71.0%) patients were in remission/low disease activity according to DAS28-ESR and 23 (74.2%) patients according to DAS28-CRP. After one year of observation, remission/low disease activity according to DAS28-ESR and DAS28-CRP had 24 (88.9%) and 23 (85.2%) patients, respectively.In the combined therapy group of OKZ + disease-modifying antirheumatic drugs (DMARDs), remission/low disease activity according to DAS28-ESR was observed in 53 (70.7%) patients and according to DAS28-CRP – in 55 (73.3%) patients by the 6th month of therapy. After 12 months, in this group 55 (78.6%) patients showed remission/low disease activity according to DAS28-ESR and according to DAS28-CRP – 58 (82.9 %) patients.After 6 months, 107 (97.3 %) out of 110 patients included in the study continued treatment. In 1 (0.9%) case OKZ was discontinued due to insufficient effect, in 2 cases contact with the patients was lost. After 12 months, therapy was continued in 97 (88.2%) patients. In 5 (4.5%) cases treatment was discontinued due to insufficient efficacy, in 2 (1.8%) cases – due to increased AST/ALT levels, in another 2 (1.8 %) cases – for non-medical reasons, and in 1 case contact with the patient was lost.Conclusion. OKZ, a direct IL-6 inhibitor, provided effective control over RA symptoms after switching from iIL6R, which allowed to achieve the treatment goal of maintaining remission/low disease activity over 1 year in more than 80% of patients. OKZ has demonstrated a broad spectrum of capabilities in real-world clinical practice, even when used as monotherapy. In terms of safety profile, OKZ was comparable to other IL6 inhibitors.

Influencers of Achievement of Remission and Low Disease Activity in Response to Disease-Modifying Antirheumatic Drugs (DMARDs) in Patients With Rheumatoid Arthritis

Influencers of Achievement of Remission and Low Disease Activity in Response to Disease-Modifying Antirheumatic Drugs (DMARDs) in Patients With Rheumatoid Arthritis

Celecoxib in rheumatic diseases: possibilities and prospects. Brief descriptive survey

Chronic pain is the main manifestation of rheumatic diseases (RD), it determines the main complaints and worsens the quality of life of patients. The problem of effective control of chronic pain in rheumatology remains a current issue despite the successes in the development of new drugs for pathogenetic therapy, especially in immunoinflammatory RD. For example, 40-50% of patients with rheumatoid arthritis (RA), even those receiving biologic disease-modifying antirheumatic drugs and Janus kinase inhibitors, require analgesics. According to several population studies, about 50% of patients with the most common RD, osteoarthritis (OA) are forced to take various analgesics on a regular basis.The most popular class of analgesics with proven efficacy in RA, spondyloarthritis (SpA) and OA are non-steroidal anti-inflammatory drugs (NSAIDs). As has been shown in several meta-analyses, NSAIDs are superior to placebo and paracetamol in their therapeutic effect, are not inferior to opioids and are better tolerated overall. However, the use of NSAIDs can be associated with the development of dangerous adverse events (AEs), which requires careful monitoring of the patient's condition, considering comorbid diseases and risk factors. It is very important to choose a drug with a balanced ratio of efficacy and low risk of gastrointestinal and cardiovascular AEs. One such drug is celecoxib, whose therapeutic potential and relative safety have been confirmed in RA, SpA and OA. A differentiated approach to celecoxib prescription makes it possible to achieve a maximum therapeutic result with a minimum risk of AEs. For severe pain, treatment starts with a dose of 400 mg/day, followed by a switch to a maintenance dose of 200 mg/day.

Steroid-sparing strategy for the treatment of vasculitis associated with antineutrophil cytoplasmic antibodies

Glucocorticoids (GC) and immunosuppressants (IS) are traditional treatments for vasculitis associated with antineutrophil cytoplasmic antibodies (ANCA), often resulting in the development of infections, diabetes mellitus and other adverse events (AEs). The development of a steroid-sparing strategy using biologic disease-modifying antirheumatic drugs (bDMARDs, including rituximab, etc.) and synthetic targeted drugs (avacopan) has radically improved the course of the disease. Currently, there are increasing number of basic and clinical trials of numerous bDMARDs that effectively reduce the number of AEs associated with GC and IS. The steroid-sparing therapeutic strategy not only shows considerable efficacy, but also opens up new perspectives for the treatment of patients with ANCA-associated systemic vasculitis.

Efficacy and safety of the biosimilar etanercept in the treatment of patients with rheumatoid arthritis and spondyloarthritis

Objective: to evaluate the efficacy and safety of the biosimilar etanercept (ETC, Altebrel) in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) in clinical practice.Material and methods. The study included 20 patients with a confirmed diagnosis of RA and 8 with SpA: 5 with axial SpA with radiological signs of sacroiliitis (r-axSpA), 3 with peripheral psoriatic arthritis (PsA). The mean age of the patients with RA was 47.7±12.3 years, and the mean age of SpA patients was 40.4±15.9 years. Patients with RA had moderate or high disease activity: mean DAS28-ESR index 5.2±1.0, median CDAI – 22.5 [15.5; 35.0], SDAI – 31.9 [24.4; 38.6], CRP level – 11 [0.9; 32.5] mg/L. Patients with r-axSpA had high activity and functional impairment, the median BASDAI was 5.5 [3.5; 8.0], BASFI – 6 [4; 6], CRP level – 17.5 [12.5; 27] mg/L. In PsA, the average DAS28 was 6.25±0.71. All patients were prescribed Altebrel at a dose of 50 mg subcutaneously weekly against a background of disease-modifying antirheumatic drugs. Patients were examined at baseline and then after 3 and 6 months of treatment.Results and discussion. During treatment with the biosimilar ETC, all patients with RA showed a decrease in inflammatory activity markers: after 3 and 6 months of therapy, the mean DAS28-ESR value decreased to 3.5±1.2 and 2.3±0.7 (p &lt;0.001) the median SDAI value to 19.6 [6.9; 32.5] and 8.4 [4.7; 15.6] (p&lt;0.001), CDAI value to 9.5 [4; 13.0] and 4.5 [3.0; 7.5] (p &lt;0.001), the CRP level – to 5.0 [0.7; 21.9] and 5.0 [2.0; 10.9] mg/L (p&lt;0.001), respectively. Patients with SpA showed a decrease in disease activity and an improvement in functional status: the median BASDAI decreased to 1.0 [0; 2.5] and 0 [0; 1.5], BASFI to 0 [0; 1] and 0 [0; 0], CRP level to 4.5 [2.5; 6.5] and 2.0 [2.0; 2.5] mg/L, respectively. In patients with PsA, DAS28 decreased on average to 2.92±0.12 after 3 months, and after 6 months the values were 1.74 and 2.29 in 2 patients.All patients completed the study and no adverse events were observed during treatment. According to EULAR criteria, a good response was achieved in 40% of patients with RA after 3 months, and in 80% after 6 months, and a satisfactory response in 20%. Patients with r-axSpA showed statistically significant positive dynamics of BASDAI and BASFI indices as well as normalization of laboratory activity parameters.Conclusion. The results of the study demonstrate the high efficacy of Altebrel in rheumatic diseases, including RA and SpA.