Disease-modifying Antirheumatic Drug Therapy Research Articles

Racial and Ethnic Disparities in Treatment Initiation Among Patients with Newly Diagnosed Psoriatic Arthritis: A Retrospective Medicaid Claims Database Study.

In patients with psoriatic arthritis (PsA), potential differences in care by race/ethnicity have not been well studied. This retrospective, observational cohort analysis utilized the IBM MarketScan® Multi-State Medicaid database. Patients aged ≥ 18years with two or more PsA-related claims between January 1, 2010 and December 31, 2019, and ≥ 12months of continuous enrollment before the first diagnosis of PsA (index date) were included. Outcomes evaluated were the use of disease-modifying antirheumatic drugs (DMARDs) overall and by type (conventional synthetic, biologic, targeted synthetic) within 12months following initial PsA diagnosis, as well as the time to DMARD initiation after initial PsA diagnosis, stratified by race/ethnicity. Multivariate Cox proportional hazards models were used to assess potential associations between patient baseline characteristics and time to DMARD initiation. Among patients with newly diagnosed PsA (N = 3432), the mean age was 44.4years, 69.9% were female, 77.4% were White, and 10.1% were Black. Of the 2993 patients with at least 12months of follow-up, fewer Black patients received any DMARD therapy compared with White patients (68.4 vs. 76.4%, respectively, p = 0.002), and, specifically, a lower percentage of Black patients received biologic DMARDs compared with White patients (33.6 vs. 42.6%, respectively, p = 0.003). After adjusting for baseline characteristics, Black patients had significantly longer time to initiation of any DMARD (HR [95% CI] 0.82 [0.71-0.94]) and biologic DMARD (0.84 [0.71-0.99]) compared with White patients. Other baseline variables such as older age, anxiety, and hepatitis C were also significantly associated with longer time to any DMARD initiation after initial PsA diagnosis. Time to treatment initiation was significantly longer in Black patients compared with White patients with newly diagnosed PsA. These findings suggest care delivery disparities in patients with PsA and highlight the need for future studies to understand factors that drive the observed differences in drug therapy by race/ethnicity.

The association between neutrophil-to-lymphocyte ratio and disease activity in rheumatoid arthritis.

The inflammatory response is responsible for the promotion of pannus development over the joint, which is the primary factor in joint injury in rheumatoid arthritis (RA). More in-depth investigations have been conducted in recent years leading to a greater understanding of RA. Yet, it's difficult to gauge inflammation levels in RA patients. Some people who have RA do not exhibit normal symptoms, which makes it more challenging to make a diagnosis. Typical RA evaluations are subject to a few restrictions. Earlier research demonstrated that some patients continued to experience the progression of bone and joint degeneration even while in clinical remission. This progression was attributed to ongoing synovial inflammation. As a result, performing a precise evaluation of the level of inflammation is of the utmost importance. The neutrophil-to-lymphocyte ratio (NLR) has consistently been one of the most interesting novel non-specific inflammatory indicators. It is a reflection of the equilibrium between lymphocytes and neutrophils, which are inflammatory regulators and inflammatory activators, respectively. A higher NLR is linked to more severe levels of imbalance and inflammation. The aim of this study was to depict the role of NLR in RA progression and to show if NLR could predict the response to disease-modifying antirheumatic drugs (DMARDs) therapy in RA.

CHANGE IN ARTERIAL STIFFNESS AND AMBULATORY BLOOD PRESSURE IN PATIENTS WITH RHEUMATOID ARTHRITIS: THE JOINTHEART STUDY

Objective: Use of disease modifying antirheumatic drugs (DMARDs) has been associated with reduction in blood pressure (BP) and arterial stiffness in clinical trials, but real-word data is lacking. We investigated change in ambulatory BP and arterial stiffness in outpatients with rheumatoid arthritis (RA) eligible for initiation or change in targeted synthetic (ts) or biological (b) DMARDs. Design and method: Eighty-nine consecutive RA patients (age 53±13, 68% women) were examined at initiation of ts/bDMARDs and repeated after 22 months. Ambulatory BP, carotid-femoral-pulse wave velocity (cfPWV) and Disease Activity Score in 28 joints using C-reactive protein (DAS28) were measured at baseline and at follow-up. High cfPWV was defined as cfPWV > 10 m/s in accordance with guidelines. Results: At follow-up, 20% used tsDMARDs, 57% bDMARDs and 67% had achieved remission or low disease activity. DAS28 decreased from 3.9±1.3 at baseline to 2.8±1.2 at follow-up (p<0.001). The ambulatory systolic BP increased (116±11 mmHg vs 120±13 mmHg, p = 0.010), while the ambulatory diastolic BP decreased (76±7 mmHg vs. 73±8 mmHg, p = 0.001) from baseline to follow-up. Body mass index (BMI) increased from 26.5±5.2 kg/m2 to 27.1±4.9 kg/m2, p = 0.009. Changes in ambulatory systolic and diastolic BP were associated with presence of diabetes at baseline, but not DAS28 or use of ts or bDMARDs. Mean cfPWV increased from 7.8±1.6 m/s at baseline to 8.5±1.8 m/s at follow-up (p<0.001). The prevalence of high cfPWV increased from 10.8% to 16.3 %, p = 0.03. DAS28 (beta = 0.32, p = 0.01) and diabetes at baseline (beta = 0.39, p = 0.001) were associated with increase in cfPWV, independent of achieved remission/low disease activity at follow-up, baseline systolic BP, BMI, age, sex and use of antihypertensive drugs. Conclusions: In outpatients with RA, higher disease activity at baseline was associated with an increase in arterial stiffness during follow-up, despite DMARD therapy and significant decrease in disease activity.

A review on pharmacokinetics of sinomenine and its anti-inflammatory and immunomodulatory effects.

Autoimmune diseases (ADs), with significant effects on morbidity and mortality, are a broad spectrum of disorders featured by body's immune responses being directed against its own tissues, resulting in chronic inflammation and tissue damage. Sinomenine (SIN) is an alkaloid isolated from the root and stem of Sinomenium acutum which is mainly used to treat pain, inflammation and immune disorders for centuries in China. Its potential anti-inflammatory role for treating immune-related disorders in experimental animal models and in some clinical applications have been reported widely, suggesting an inspiring application prospect of SIN. In this review, the pharmacokinetics, drug delivery systems, pharmacological mechanisms of action underlying the anti-inflammatory and immunomodulatory effects of SIN, and the possibility of SIN as adjuvant to disease-modifying anti-rheumatic drugs (DMARDs) therapy were summarized and evaluated. This paper aims to reveal the potential prospects and limitations of SIN in the treatment of inflammatory and immune diseases, and to provide ideas for compensating its limitations and reducing the side effects, and thus to make SIN better translate to the clinic.

IFABP2 as a new prognostic biomarker for secondary non-response in rheumatoid arthritis

Increased intestinal permeability promotes the translocation of bacterial products from the local microbiome to the circulation, inducing inflammation and increasing clinical activity in rheumatoid arthritis (RA). This study evaluates whether intestinal fatty acid binding protein 2 (IFABP2) serum levels are prognostic biomarkers of non-response to conventional synthetic disease-modifying antirheumatic drug therapy (csDMARDs) in RA. The therapeutic schemes administered to 60 women with RA for at least 18months were assessed retrospectively, and the treatment response was classified according to the change in DAS28-ESR over time. Serum levels of IFABP2 and TNF-α were determined by ELISA. Receiver operating characteristics (ROC) curve analysis and logistic regression models were used to assess the predictive value and the association of IFABP2 with the non-responder phenotype in RA patients. Eleven women had a responder phenotype, 23 had a primary non-responder phenotype, and 26 had a secondary non-responder phenotype. Secondary non-responders showed higher DAS28-ESR (P=0.009) and higher IFABP2 serum levels compared to the responder group (P=0.023) and the primary non-responder group (P=0.018). IFABP2 serum levels were positively correlated with chloroquine dose (r=0.581, P=0.007) and negatively correlated with total cholesterol (r=-0.456, P=0.019) in secondary non-responders. The area under the curve (AUC) value of IFABP2 for predicting secondary non-response was 0.736, and IFABP2 serum levels>9.311ng/mL were associated with secondary non-response to csDMARDs (OR=6.00, P=0.003). IFABP2 serum levels are potentially a new biomarker predictive of secondary non-response to csDMARDs in RA, although our findings should be validated externally and in a larger cohort.

The Role of Clock Genes in Maintaining Circadian Rhythm and Rheumatoid Arthritis Pathophysiology.

Rheumatoid arthritis (RA) is a chronic, progressive autoimmune condition that affects up to 1% of the world population and symmetrically affects the joints leading to joint stiffness and decreased mobility. RA patients present with increased pain and chronic inflammation within their joint spaces, which researchers have linked to poorer sleep patterns, including difficulty falling asleep and non-restorative sleep. As such, identifying mediators of poor sleep quality among RA patients may improve their long-term quality of life. More recently, researchers identified an association between chronic inflammation in RA patients and their circadian rhythm. Altered circadian rhythms negatively impact the hypothalamic-pituitary-adrenal (HPA) axis and lead to altered cortisol release. Cortisol has shown to have a strong anti-inflammatory effect; when dysregulated, it may lead to increased pain experienced in RA patients. This literature review aims to provide insight into how chronic inflammation tied to RA pathophysiology may affect clock genes that are involved in maintaining the circadian rhythm. Specifically, this review focused on four common clock genes found dysregulated in RA patients: circadian locomotor output cycles kaput(CLOCK),brain and muscle ARNT like-1(BMAL1),period(PER),and cryptochrome(CRY).Of the four clock genes discussed in this review,BMAL1andPERare the most well-studied of the affected genes. Further knowledge surrounding clock genes and their dysregulated expression in RA may help guide therapy decisions for RA patients. Traditionally, disease-modifying antirheumatic drugs (DMARDs) have been used as first-line therapy for RA patients. Meanwhile, chronotherapy, optimizing drug release in a timed manner, has shown positive results in RA patients as well. Because of the association of altered circadian rhythms with increased symptom severity in RA patients, it seems highly plausible that DMARD therapy with chronotherapy may be an ideal therapeutic regimen for RA.

Features of clinical manifestations of rheumatoid arthritis in patients after failure of conventional synthetic disease-modifying antirheumatic drugs therapy depending on the signs of central sensitization

Central sensitization (CS) is a condition characterised by (associated with) neuroplastic changes in nociceptive neurons, sub-threshold afferent input, pain hypersensitivity and development widespread pain. Insufficient response to disease-modifying antirheumatic drugs (DMARDs) can be caused by CS.Objective – to evaluate the features of clinical manifestations of RA in patients with ineffective antirheumatic therapy, depending on the presence of signs of CS.Material and methods. The study group included 509 patients diagnosed with RA (according to ACR/EULAR classification criteria, 2010) with moderate or high disease activity (DAS28-CRP≥3.2) and ineffectiveness or intolerance of conventional synthetic DMARDs, biological DMARDs and JAK inhibitors. Disease activity in patient with RA was assessed by DAS28-CRP. Our study did not include an examination by a neurologist to detect signs of CS, so the Central Sensitization Inventory (CSI) (part one) was used. The BPI questionnaire was used for assessing clinical pain intensity. The PainDETECT, FSS, FIRST, HAQ questionnaires were used for screening neuropathic pain symptoms (NPS), fatigue, fibromyalgia signs and functional impairment, respectively. The HADS questionnaire was recommended for early diagnosis anxiety and depression disorders.Results. Signs of CS (CSI≥40), with a median of 42 [32; 53], were found in 57.2% of the examined patient. Patients with signs of CS were established to have poorer health measure (PGA – 64.6±13.5 and 53.5±16.8; p=0.001), higher pain intensity in all BPI scales, longer morning stiffness – 90 [30; 180] and 60 [20; 120] minutes (p=0.001), more painful joints – 8 [5; 12] and 7 [4; 10] (p=0.005), worse functional status in HAQ (1.65±0.7 and 1.08±0.5; p=0.001) and higher disease activity in DAS28-CRP (4.9±1.0 and 4.6±0.9; p=0.001) compared to patients without signs of CS. There was also direct correlation between CS and a high frequency of having an NPS (PainDETECT>18) – 34.5% and 10.3% (p=0.001), significant anxiety and depression (HADS>11) – 29,0% and 5.1% (p=0.001) and 26.3% and 4.2% (p=0.001) respectively, fatigue (FSS) – 96.5% and 70.4% (p=0.001), signs of fibromyalgia (FIRST≥5) – 38.4% and 6.1% (p=0.001).Conclusion. The presence of signs of CS in patient with RA significantly enhance many symptoms of disease, being associated with higher pain intensity, fatigue, impaired function, higher incidence of NPS, depression and anxiety, and fibromyalgia.

P089 A pilot study to consider implementing a validated tool to improve the objective assessment method of methotrexate intolerance for a paediatric rheumatology department

Abstract Background/Aims This report identifies if the adoption of the Methotrexate Intolerance Severity Score improves the documentation and objective evaluation of the experiences of patients with Juvenile Idiopathic Arthritis, currently treated with methotrexate within in a local paediatric rheumatology service. In doing so, it will evidence any treatment failure resulting in a change of therapy, including the advocated escalation to more expensive and invasive biological therapies. Methods Literature was retrieved from electronic databases and published guidelines. Stakeholders were identified and approached via a variety of methods. Using the claims, concerns and issues framework to document their findings, a pilot study implementing the validated methotrexate intolerance severity score was conducted. The parents of the first ten patients accessing the local paediatric rheumatology advice line within a twelve-week period, who wished to discuss their child’s methotrexate therapy, were interviewed by the clinical nurse specialist team according to the methotrexate intolerance severity score. Analysis of the ten telephone assessments included the patient pharmacological and haematological evidence already established for each child, previous documentation of any methotrexate intolerance, and previous awareness of potential side effects of this drug therapy Results Designed without key stakeholder input, the methotrexate intolerance severity score improved documentation but focused on the gastrointestinal symptoms of intolerance only. The results of this pilot project indicated that although nausea and vomiting remained the two most common problems identified by all three key stakeholder groups (the parents, the CNS team and the original MISS article), it failed to objectively record a number of other commonly experienced signs and symptoms attributed to methotrexate treatment, assessing intolerance using only four of the nine most commonly reported side effects. Crucially it also failed to consider the pharmacokinetic and toxicity profile of methotrexate, nor did it have capacity to document a range of other parent reported symptoms. Although published in 2011, it has yet to be adopted for regular use within the UK paediatric rheumatology services. Conclusion Further work is required; inclusion of the objective findings that contribute to and mimic methotrexate intolerance e.g., hepatotoxicity should be considered in addition to further research regarding the patient experience of methotrexate intolerance. Incorporating the experiences of the patients and families would contribute to the relevance of the methotrexate intolerance severity score to key stakeholders. Resulting in a more objective assessment tool, this would improve measurement of methotrexate intolerance, ultimately quantifying intolerance and access to biologic therapies and improve the clinical comprehension of the patient experience of this ‘gold standard’ disease modifying anti-rheumatic drug therapy. Disclosure C. Tranter: None.

P007 Automating blood monitoring and handover for patients with rheumatic diseases commencing disease-modifying anti-rheumatic drugs (DMARDs)

Abstract Background/Aims Approximately 100 patients a month are commenced on DMARD therapy and until recently required manual monitoring and handover to primary care. We aimed to improve this process using a system implementing automated algorithms. Methods We designed a system to automate analysis using algorithms based on BSR guidance. Clinician endorsement was required for individual missing and abnormal results. Group endorsement was enabled for normal and mildly abnormal results. Handover to primary care was facilitated by patients completing a Microsoft form providing details of efficacy, side-effects, and compliance. All reports are imported into our bespoke system to generate automatic reports which constituted as a handover letter to primary care Results We have analysed 5,483 blood tests using the new system. All normal results can be endorsed at once without scrutiny. Missing records occurred chiefly due to the laboratory providing blood results in sections. The new system has been tested against the manual method for blood monitoring highlighting improved accuracy and efficiency of the new system. To date, 69% of patients have been handed over to the GP successfully without a need for further out-patient appointment. Conclusion We have introduced an efficient method for semi-automating DMARD monitoring and handover in 5,483 sets equivalent to assessing 200-250 records per 4-hour session and could efficiently oversee handover in 69% of cases without necessitating direct clinical review. The efficiency is almost 80% reduction in workforce required. Disclosure M. Mirza: None. D. Lang: None. A. Escudero: None. A. Soni: Grants/research support; Oxford ucb grant. B. Shine: None. K. Paddon: None. R. Luqmani: Grants/research support; Pfizer global grant.

E056 C-reactive protein rise in rheumatology patients following COVID-19 vaccination

Abstract Background/Aims With widespread implementation of COVID-19 vaccine, there has been concern that it would trigger an immune activation due to its immunogenic properties. There is low-level evidence that patients with rheumatological diagnosis often have a disease flare following COVID-19 vaccination which not only has personal health implications but also wider socioeconomic implications. Inflammatory arthritis patients are classified as vulnerable patients requiring booster vaccinations. Therefore, there is a need to ascertain whether there is a risk of disease flare in this group of patients so as to counsel them appropriately in order to ensure flares are managed in timely manner. This study aims to determine the proportion of patients with inflammatory arthritis who have a flare of their rheumatological disease within 30 days of receiving a COVID-19 vaccine using CRP as a surrogate marker. Methods A retrospective notes review was conducted of patients with inflammatory arthritis within 30 days of their COVID-19 vaccine. An electronic database (DAWN) was used to identify all patients that were currently on a disease-modifying anti-rheumatic drug (DMARD) or biologic therapy. This was then correlated with vaccine data from the National Immunisation and Vaccination system (NIVS) and C-reactive protein (CRP) within 30 days of their vaccination. Results 1620 adults were identified from DAWN databases (mean age 61 years, 64% female). Three types of vaccination were used: AstraZeneca (AZ), BioNTech-Pfizer or Moderna. Vaccine uptake was 1542/1620 (95.2% 1st dose), 1550/1620 (95.7% 2nd dose) and 1437/1620 (88.7% 3rd dose). 192/1542 patients (12.5%) had a CRP rise of greater than 10mg/L within 30 days of their vaccine, which was higher than baseline flare rate of 8.6% (p = 0.0004). Conclusion Patients with inflammatory arthritis and on DMARDS have high uptake of COVID-19 vaccine (95%) which is greater than the national average. A CRP rise greater than 10mg/L within 30 days of vaccination was observed in roughly 1 in 10 patients in our study population on all three doses which is consistent with other studies in the literature. Our results show statistically significant increase in the rate of disease flare (12.5% compared with baseline rate of 8.6%). However, SARS-CoV-2 infection has been shown many times to be an independent risk factor for rheumatic disease flare ranging from 20-40%. Therefore, patients with inflammatory arthritis should still be encouraged to receive COVID-19 vaccination. To maintain high levels of vaccine uptake, it is important to ensure that patients are aware of the risks of vaccinations and sufficiently safety netted so flares are managed early. As on-going booster vaccinations are planned for rheumatology patients, we recommend further research to better inform and counsel our patients. Furthermore, this study calls for diligence in monitoring patients with inflammatory arthritis for disease flare and for swift intervention to prevent losing disease control. Disclosure S. Kim: None. S. Gor: None. K. Yein: None. J. Michael: None. E. Price: None.

E008 I feel a bit happier about going on it now: exploring the information needs of people starting methotrexate

Abstract Background/Aims Methotrexate (MTX) is recommended as initial disease-modifying anti-rheumatic drug (DMARD) therapy for people with rheumatoid arthritis (RA). Rheumatology nurses provide information about benefits, risks and safety monitoring requirements for methotrexate during DMARD counselling, which may be provided in different formats. This study sought to explore the information needs and experiences of people with RA commencing MTX. Methods Seventy-six adults with RA referred for MTX DMARD counselling attending two rheumatology units in the West Midlands were invited to take part in qualitative semi-structured interviews (either by phone or video) before and after receiving information about MTX. Research partners with RA helped to develop interview topic guides. Interviews were digitally recorded, transcribed and analysed using reflexive thematic analysis. Results Nineteen participants, (11 male, 8 female, White British, age 45-76 years, disease duration 6 weeks - 35 years) took part in telephone (n17) or video (n2) interviews (duration 34-82 minutes). Three main themes were identified: information delivery, necessity of MTX and concerns about MTX. Information delivery: most participants received telephone DMARD counselling which was helpful for people with mobility issues or work commitments. However, most acknowledged a preference for, and the importance of face-to-face communication. Information tended to be provided in a generic manner, using a checklist, and could feel rushed. Written MTX leaflets were received but not used by all participants. Some participants felt well informed whilst others felt overwhelmed with information. Many had difficulty recalling important safety information. Unmet information needs about monitoring, prescribing and follow-up arrangements were frequently reported. Inconsistent information about MTX from different sources could increase concerns. Rheumatology helplines were valued as a direct route to information and care. Necessity of MTX: most participants wanted more information on why they should take MTX, how and when MTX would help them and how long they would be required to take MTX for. Some wanted to know about other drug treatment options. Concerns about MTX: all participants had concerns about the likelihood and severity of side-effects including mouth ulcers, nausea and hair loss. Worries about the use of MTX as a cancer treatment were frequently reported. Whilst concerns remained about MTX most participants accepted the risk of side-effects because of the need to improve their symptoms. Conclusion DMARD counselling was valued by people with RA when starting MTX but was not always responsive to information needs. Addressing individual concerns about the necessity for MTX, concerns about side-effects and prioritising essential safety information is recommended. Practical issues around obtaining supplies of MTX, monitoring, follow-up arrangements and a follow-up telephone call may help address unmet information needs for some. Disclosure S.J. Logan: None. S. Hider: None. J. Green: None. S. Ryan: None.

Evaluation of clinical efficacy of tumor necrosis factor‑α inhibitors in treatment of distal extremity swelling with pitting edema in psoriatic arthritis of inadequate response to conventional therapy: A 10‑year retrospective study.

Distal extremity swelling with pitting edema in psoriatic arthritis (PsA) is a rare rheumatological condition, whose management presents a challenge. The aim of the present study was to identify the clinical characteristics of, and formulate a standardized management strategy for, patients with distal extremity swelling with pitting edema in PsA. The medical records of consecutive patients with PsA, with or without distal extremity swelling with pitting edema, were systematically analyzed over a ~10-year period (between September 2008 and September 2018) in a single center and a comprehensive review (pathogenic mechanisms, clinical manifestations, and treatments) was undertaken. A total of 167 patients with PsA were evaluated, and distal extremity swelling with pitting edema was recorded in 16 of these patients. In three of the 16 patients, distal extremity swelling with pitting edema occurred as the first, isolated manifestation of PsA. The upper and lower extremities were affected, predominantly asymmetrically. Female patients with PsA were more likely to be affected with pitting edema and the blood test results revealed that the patients with PsA and pitting edema also presented with a significantly higher erythrocyte sedimentation rate and concentration of C-reactive protein. The onset of pitting edema was associated with the activity of the disease. Lymphoscintigraphy and magnetic resonance imaging (MRI) scans revealed that edema might have resulted from inflammation of the tenosynovial structures. Furthermore, treatment with tumor necrosis factor-α inhibitor (TNFi) elicited improvements in patients with pitting edema that were not responsive to conventional synthetic disease-modifying antirheumatic drug therapy. In conclusion, distal extremity swelling with pitting edema, also termed atypical remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome, may represent the initial isolated manifestation of PsA. The atypical RS3PE syndrome in PsA was attributable to inflammation of the tenosynovial structures, and TNFi may serve as a potential treatment.

Etanercept for patients with juvenile idiopathic arthritis: drug levels and influence of concomitant methotrexate: observational study

BackgroundEtanercept (ETN) is widely used tumour necrosis factor (TNF) blocker in the treatment of juvenile idiopathic arthritis (JIA) when traditional synthetic disease modifying antirheumatic drug (sDMARD) therapy is not sufficient. There is limited information about the effects of methotrexate (MTX) on serum ETN concentration in children with JIA. We aimed to investigate whether ETN dose and concomitant MTX would effect ETN serum trough levels in JIA patients, and whether concomitant MTX have an influence on the clinical response in patients with JIA receiving ETN.MethodsIn this study, we collected the medical record data of 180 JIA patients from eight Finnish pediatric rheumatological centres. All these patients were treated with ETN monotherapy or combination therapy with DMARD. To evaluate the ETN concentrations, blood samples of the patients were collected between injections right before the subsequent drug. Free ETN level was measured from serum.ResultsNinety-seven (54%) of the patients used concomitant MTX, and 83 (46%) received either ETN monotherapy or used sDMARDs other than MTX. A significant correlation was noted between ETN dose and drug level [r = 0.45 (95% CI: 0.33–0.56)]. The ETN dose and serum drug level were correlated (p = 0.030) in both subgroups – in MTX group [r = 0.35 (95% CI: 0.14–0.52)] and in non-MTX group [r = 0.54 (95% CI: 0.39–0.67)].ConclusionIn the present study, we found that concomitant MTX had no effect on serum ETN concentration or on clinical response. In addition, a significant correlation was detected between ETN dose and ETN concentration.

High burden of polypharmacy and comorbidity in persons with psoriatic arthritis: an analysis of claims data, stratified by age and sex

ObjectiveTo assess polypharmacy in women and men with psoriatic arthritis (PsA).MethodsFrom the German BARMER health insurance database, 11 984 persons with PsA and disease-modifying antirheumatic drug therapy in 2021 were...

The National Prevalence of Clinically Diagnosed Psoriatic Arthritis in Sweden 2017.

Psoriatic arthritis (PsA) prevalence estimates vary across studies; studies based on national data are few. We aimed to estimate the prevalence of clinically diagnosed PsA in Sweden in 2017, overall and stratified by sex/age/education/geography, and to quantify disease-modifying anti-rheumatic drug (DMARD) use among those in contact with specialized rheumatology care 2015-2017. Individuals, 18-79 years (y), alive, residing in Sweden on December 31, 2017, with a prior PsA diagnosis were identified from the National Patient Register (NPR) and/or the Swedish Rheumatology Quality Register (SRQ). The PsA prevalence was estimated according to a base case (BC) definition (≥1 main PsA ICD-code from rheumatology or internal medicine departments in NPR, or a PsA diagnosis in SRQ), four sensitivity analysis definitions, and for those seen in specialized rheumatology care 2015-2017. In the latter group, DMARD use during 2017 was also assessed. Data for stratifications were retrieved from national registers. The crude national prevalence of PsA (18-79y) was estimated at 0.39% (BC), 0.34% after accounting for diagnostic misclassification and 0.32-0.50% across all sensitivity analyses. The prevalence was lower in males and in those with higher level of education. The prevalence for those seen in specialized rheumatology care 2015-2017 was estimated at 0.24%. In this population, 32% received biologic or targeted synthetic DMARDs, and 41% conventional synthetic DMARDs only, during 2017. The prevalence of clinically diagnosed PsA (18-79y) in Sweden in 2017 was around 0.35%. Among PsA cases in recent contact with specialized rheumatology care, almost 3/4 received DMARD therapy in 2017.

The Cost-Effectiveness of and Adherence to Disease-Modifying Antirheumatic Drug (DMARD) Therapy in Rheumatoid Arthritis Patients in a Tertiary Care Teaching Hospital in Uttarakhand, India.

Objective This study was conducted with the aim ofevaluating the cost-effectiveness of and adherence to treatment in patients on disease-modifying antirheumatic drug (DMARD) therapy for rheumatoid arthritis (RA) in a tertiary care teaching hospital in Uttarakhand, India. Methodology This prospective observational study was conducted on 150 rheumatoid arthritis patients presenting to the Rheumatology Outpatient Department (OPD) receiving DMARD therapy (approval number AIIMS/IEC/18/160). The patients were followed up for an average of 10.7 weeks and received drugs in four regimens with methotrexate (MTX) (Regimen 1) having the least contribution with a mean of 46.05 Rs, methotrexate + hydroxychloroquine(MTX + HCQ) (Regimen 2) with 174.15 Rs, methotrexate + hydroxychloroquine + leflunomide (MTX + HCQ + Lef) (Regimen 3) with Rs 371.70, and methotrexate + hydroxychloroquine + leflunomide + biological DMARD adalimumab(MTX + HCQ + Lef + bDMARD adalimumab) (Regimen 4) with 17,349.4 Rs.The cost of drug therapy was assessed by calculating the cost of therapy per month for each patient, and adherence was assessed using the Morisky-Green-Levine Scale (MGLS) at the follow-up visit. Results The overall mean cost of DMARD treatment was 205.81 Rs. The overall DMARD therapy cost-effectiveness was Rs 878.14 for a unit change of Disease Activity Score (DAS28). The most cost-effective treatment came out to be Regimen 1 with the least cost of 290.9Rs for a unit change of DAS28, and the least cost-effective was Regimen 4 with 65,661.8 Rs for a unit change of DAS28. At follow-up, among all subjects of the study, 49 (32.7%) subjects showed high adherence, 71 (47.3%) subjects showed medium adherence, and 30 (20%) subjects showed low adherence. Accordingly, the maximum number of participants fell in the category of medium adherence, i.e., 71 (47.4%). Conclusion Our study concluded that the cost burden varied according to the number of DMARDs being given to the patient. The double-drug therapy of methotrexate + hydroxychloroquine had a maximum "high adherence." On a whole, the majority of patients had "medium adherence" to therapy.

Shoulder arthroplasty trends in patients with rheumatoid arthritis receiving disease-modifying antirheumatic drug therapy

BackgroundDisease-modifying antirheumatic drugs (DMARDs) are used to treat rheumatoid arthritis (RA) and may lead to remission and decreased rates of joint arthroplasty. The rates of total shoulder arthroplasty (TSA) in RA patients since the implementation of DMARDs therapy are unknown. Furthermore, the utilization rates of TSA among various age cohorts as well as by procedure type: anatomic (ATSA) and reverse (RTSA), are not well defined in this patient population. The primary aim of this study was to assess TSA trends from 2011 to 2019 in RA patients with and without DMARD prescriptions. MethodsA retrospective trends analysis utilizing a national claims database was performed investigating the trends of TSA in RA patients with and without DMARD prescription claims from 2011 to 2019. Patients and prescriptions were identified using International Classification of Diseases codes and database-specific drug codes. Patients were divided into two cohorts: RA patients who underwent a TSA either with or without DMARD prescription claims. Patients were also stratified by age groups (≤59, 60-69, and ≥70 years) and procedure type (ATSA and RTSA) for analysis. Linear regression and compound annual growth rate were performed to compare trends of surgical utilization. Significant changes between trends were determined using an interaction term between the trend and calendar year within the regression. ResultsFrom 2011 to 2019, incidence of TSA in RA patients without DMARD prescription claims increased significantly more than in RA patients with prescription claims. Among the age groups, incidence of TSA in RA patients with and without DMARD prescription claims significantly increased among all age groups. The rate of change of TSA incidence in RA patients in all age groups was significantly higher in patients without DMARD prescription claims compared to RA patients with prescription claims. By procedure type, the incidences of RTSA were significantly increasing while incidences of ATSA were significantly decreasing in both groups. ConclusionThe incidence of TSA has increased significantly more in RA patients without DMARD prescription claims when compared to RA patients with prescription claims. Across all age groups, TSA was performed increasingly more in patients without prescription claims than in patients with prescription claims. The greater increase in TSA surgeries among patients aged 59 and younger without prescription claims suggests that DMARD therapy may play a beneficial role in preventing or delaying the need for TSA in RA patients. Examination of surgical utilization trends illustrates that RTSA is the preferred treatment over ATSA among RA patients.

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.

Pain Mechanisms Associated With Disease Activity in Patients With Rheumatoid Arthritis Treated With Disease-Modifying Antirheumatic Drugs: A Regression Tree Analysis.

Although pain affects the assessment of disease activity in patients with rheumatoid arthritis (RA), pain is not always directly related to peripheral joint inflammation. Peripheral and central nervous system regulatory mechanisms also affect pain perception. We used regression tree methodology to identify mechanisms most predictive of disease activity after disease-modifying antirheumatic drug (DMARD) treatment. Disease activity was evaluated using the Disease Activity Score in 28 joints (DAS28) in 176 patients with RA, before and after starting a DMARD. Quantitative sensory testing (QST), including pressure pain thresholds (PPTs), temporal summation, and conditioned pain modulation (CPM), were used to assess pain mechanisms. Regression tree methodology was used to determine the QST modalities most predictive of DAS28 after DMARD treatment. This analysis identified 4 groups defined by baseline DAS28 category and either knee PPT (a combined measure of peripheral and central nervous system dysregulation) or CPM (a measure of descending pain inhibition). Among patients starting with low/moderate disease activity, lower knee PPT (PPT ≤ 4.65 kgf) most strongly predicted higher posttreatment disease activity (group 1 mean DAS28 2.8 [SD 1.0] vs group 2 mean DAS28 3.5 [SD 1.0]). Among patients starting with high baseline disease activity, less efficient descending pain modulation (CPM ≤ 1.55) most strongly predicted higher posttreatment disease activity (group 3 mean DAS28 3.4 [SD 1.4] vs group 4 mean DAS28 4.6 [SD 1.1]). These results highlight the importance of identifying and treating aberrant peripheral and central pain regulation in patients with RA starting or switching DMARD therapy.

Influence of active versus placebo control on treatment responses in randomised controlled trials in rheumatoid arthritis

ObjectivesTo investigate whether treatment effects of pharmaceutical compounds compared with placebo controls are systematically different to the effects of the same compounds compared with active treatment controls in rheumatoid arthritis...