COVID-19 prophylaxis, diagnostics, and treatment in patients with rheumatic diseases. The Polish experts panel opinion.

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolves, infection management in vulnerable populations requires formalized guidance. Although low-virulence variants of SARS-CoV-2 remain predominant, they pose an increased risk of severe illness in adults with rheumatic and musculoskeletal diseases (RMDs). Several disease-specific (chronic long-grade inflammation, concomitant immunosuppression) and individual (advanced age, multimorbidity, pregnancy, vaccination status) factors contribute to excess risk in RMD populations. Various post-COVID-19 manifestations are also increasingly reported and appear more commonly than in the general population. At a pathogenetic level, complex interplay involving innate and acquired immune dysregulation, viral persistence, and genetic predisposition shapes a unique susceptibility profile. Moreover, incident cases of SARS-CoV-2 infection as a trigger factor for the development of autoimmune conditions have been reported. Vaccination remains a key preventive strategy, and encouraging active education and awareness will be crucial for rheumatologists in the upcoming years. In patients with RMDs, COVID-19 vaccines' benefits outweigh the risks. Derivation of specialized diagnostic and therapeutic protocols within a comprehensive COVID-19 care plan represents an ideal scenario for healthcare system organization. Vigilance for symptoms of infection and rapid diagnosis are key for introducing antiviral treatment in patients with RMDs in a timely manner. This review provides updated guidance on optimal immunization, diagnosis, and antiviral treatment strategies.

Access to biologics and Janus kinase inhibitors for treatment of rheumatic diseases in the biosimilars era in Poland: a nation-level study.

INTRODUCTION: By reducing treatment costs, biosimilars provide an opportunity to improve accessibility to highly effective drugs. OBJECTIVES: This study aimed to evaluate access to biologic disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKis) among patients with rheumatic musculoskeletal diseases within a 10 year timeframe in Poland. PATIENTS AND METHODS: We performed a retrospective analysis using a nationwide public payer database. RESULTS: By 2022, 11 102, 6602, and 4400 patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) were treated with bDMARDs or JAKis. Peak drug utilization was observed for adalimumab, followed by etanercept and tocilizumab. Within the study timeframe, the estimated access to innovative drugs increased from 0.8%, 1.4%, and 0.8% to 3.2%, 8.7%, and 3.5% for RA, PsA, and axSpA patients, respectively. Affordable tumor necrosis factor inhibitors (TNFis) still predominate among innovative therapeutics, but their market share declined from 87% to 46%. The number of patients treated with other bDMARDs/JAKis almost doubled within the prespecified timeframe. Overall, the average annual treatment cost per patient decreased by 60%, from 7315 EUR to 2886 EUR. Despite recent safety warnings, JAKis appear to be increasingly utilized. Additional analyses regarding the COVID­19 pandemic showed impaired access to intravenous therapies, but not subcutaneous or oral formulations. CONCLUSIONS: In Poland, biosimilars­related savings improved availability of higher­priced innovative drugs rather than less costly TNFis. Data­driven resource allocation and dedicated policy solutions facilitating access to affordable biologics are recommended.

The perspective of Polish patients with rheumatoid arthritis - treatment expectations, patient-reported outcomes, and digital literacy (the SENSE study).

Introduction: A widely accepted treat-to-target strategy for rheumatoid arthritis (RA) requires the patient's perspective in making treatment decisions. However, data on treatment preferences and expectations of Polish patients with RA are scarce. The aim of the study was to determine the satisfaction with treatment and the nature of therapeutic preferences and expectations of Polish patients with moderate to severe RA. Material and methods: Fifty-two adult Polish patients with moderately to highly active RA were asked to complete patient-reported outcomes and patient-provided information questionnaires. Additionally, patient sociodemographic and clinical data and information on patient current and planned treatment strategies were collected. Results: The mean global assessment of patient satisfaction with treatment was 64.1 ±24.6, below the level of indicating satisfaction. Rheumatoid arthritis negatively impacted patients' lives, resulting in a 37.8% impairment of work efficiency and 45% impairment of total activity. Primary treatment expectations for patients were lasting relief of RA symptoms, reduced pain and swelling in joints, increased flexibility of joints, and general improvement of arthritis. The most acceptable potential side effect was weight gain and the least acceptable were increases in the risk of cardiovascular disease, infection, and malignancies. The rapid onset of the drug effect (up to 1 week) was a preference of 48.1% of patients. Access to internet health resources was important for 44.2% of patients, but the median total eHealth literacy score in the study population was 24.0 (interquartile range: 20.5-28.0, range 8-37), which means low digital health literacy (DHL). Conclusions: Understanding these treatment preferences and expectations of patients with RA is essential for clinical practitioners to facilitate shared treatment decision-making. Digital health literacy data suggest the need of further improvement.

Budget impact analysis and treatment availability with biosimilar TNF inhibitors in rheumatic diseases in Poland: real-world evidence using a nationwide database.

OBJECTIVES: Although several years have passed since biologic disease modifying antirheumatic drugs were introduced to the market, considerable disparities in access still remain. Tumour necrosis factor inhibitors (TNFi) have proven to be highly effective and safe for treating patients with rheumatic musculoskeletal diseases (RMDs). The emergence of biosimilars is promising for cost reduction and more equitable, widespread access. METHODS: A retrospective budget impact analysis based on final drug prices was conducted using 12 687 treatment courses for infliximab, etanercept and adalimumab. Estimated and real-life savings for public payer were calculated from an 8-year perspective of TNFi use. Data on the treatment cost and on the evolution in the number of patients treated was provided. RESULTS: From a public payer perspective, the estimated total savings amount to over €243 million for TNFi, with over €166 million attributed to treatment cost reduction in RMDs. Real-life savings were calculated as €133 million and €107 million, respectively. The rheumatology sector generated between 68% and 92% of total savings across models, depending on the adopted scenario. The overall decrease in mean annual cost of treatment ranged between 75% and 89% in the study frame. If all budget savings were spent on reimbursement of additional TNFi, a hypothetical total of almost 45 000 patients with RMDs could be treated in 2021. CONCLUSIONS: This is the first nation-level analysis that shows estimated and real-life direct cost-savings for TNFi biosimilars. Transparent criteria for reinvesting savings should be developed on both a local and an international levels.

Multicenter evaluation of tofacitinib retention and safety in rheumatoid arthritis - why cardiovascular risk factors do not equate to overt risk.

Introduction: This multicenter, real-world, retrospective cohort study aimed to assess the effectiveness and safety of tofacitinib (TOFA) in rheumatoid arthritis (RA). Material and methods: Two hundred nine patients with active RA treated with TOFA, unresponsive to at least 2 conventional synthetic disease-modifying drugs, were recruited. Clinical characteristics were extracted from an electronic registry and supplemented with manual chart review and data linkage with ambulatory care. Drug retention and reasons for discontinuation were evaluated. Results: Median (interquartile range) follow-up in the whole sample was 16.9 (5.93-31.7) months. Mean (standard deviation) age was 51.44 (±11.84) years, with female predominance (n = 168, 80.4%). Only 30 patients (14.4%) had no pre-existing traditional cardiovascular (CV) risk factor at TOFA initiation. Tofacitinib retention rates were high, with median survival estimated at 89.3% at 6 months, 82.4% at 12 months, and 60.4% at 24 months. Ineffectiveness was the primary cause of discontinuation (n = 50). The rate of adverse events (AEs) was relatively low, with lipid abnormalities, blood count alterations, and infectious events among the most common. No major adverse CV event was reported. The incidence rate of AEs necessitating treatment switch was 60.34 (95% CI: 37-92) per 1,000 person-years of follow-up. Presence of multiple (> 3) CV risk factors was associated with lower odds of TOFA retention and treatment effectiveness. Conclusions: Tofacitinib demonstrated high retention rates and a favorable safety profile in RA patients, including those with traditional CV risk factors. Tofacitinib may be a valuable treatment option for RA patients when combined with individualized CV risk management. Further studies are warranted to explore the long-term effects of TOFA and its CV impact in larger populations.

Tocilizumab as a first-line biologic treatment in rheumatoid arthritis patients - the impact of concomitant methotrexate treatment and Rheumatic Disease Comorbidity Index on the clinical response - results from the multicenter observational ACT-POL study.

Objectives: According to the EULAR recommendations, remission or low disease activity (LDA) in rheumatoid arthritis should be achieved by a maximum of 6 months (M6) of treatment. Data on the use of tocilizumab (TCZ) as first-line biologic treatment in rheumatoid arthritis (RA) in routine clinical practice in Poland are lacking. Material and methods: This multicenter, non-interventional, prospective, observational study recruited adults, presenting with moderate-to-severe RA, showing an inadequate response or intolerance to disease-modifying antirheumatic drugs, where TCZ was the first-line biologic treatment. The effectiveness of TCZ was assessed by the proportion of patients achieving remission and low disease activity following 6 months of treatment with intravenous TCZ. The impact of comorbidities on treatment outcomes was measured using the Rheumatic Disease Comorbidity Index (RDCI). Results: Total remission rates at months 3 and 6 were 6% and 31%, respectively. Low disease activity was reported in 10% and 92% of the patients at 3 and 6 months, respectively. The response was comparable between TCZ as monotherapy and in combination with methotrexate. Mean DAS28 decreased from 6.61 at baseline to 4.27 at the scheduled time of the assessment (3 and 6 months). The Rheumatic Disease Comorbidity Index was not correlated with the number of patients achieving LDA at M3 and M6 or remission rates at M6. Remission rates correlated with RDCI at M3. A total of 114 adverse events were reported in 61 patients, among which five were considered as serious. Conclusions: The study confirms the effectiveness and safety of TCZ in real-world settings as a first-line biologic treatment in patients with moderate-to-severe RA. Importantly, comorbidities do not affect the results of 6-month treatment with TCZ, that is, the optimal time to achieve at least LDA. Our results may improve the effects of RA therapy in Poland, especially in patients with comorbidities and those who, for various reasons, cannot receive optimal treatment with methotrexate.

Deep dive into achieving the therapeutic target: results from a prospective, 6­month, observational study nested in routine rheumatoid arthritis care.

INTRODUCTION: Achieving remission or lowdisease activity (LDA) is an integral principle of treat­to­target (T2T) strategy in rheumatoid arthritis (RA). Prior studies have reported that achieving T2T therapeutic goals may be realistic only for a fraction of patients. Prospective, real­world data on achieving target disease control in ambulatory care populations are limited for Central and Eastern European countries. OBJECTIVES: The aim of the study was to analyze the efficacy of treatment and determine simple predictors of achieving T2T therapy goals in daily RA practice. PATIENTS AND METHODS: This multicenter, 6­month study evaluated therapy outcomes and clinical characteristics of 791 consecutive RA outpatients, meeting the preset criteria of inadequate disease control. RESULTS: Only 9% of RA patients achieved remission or LAD after 3 months and 35% after 6 months. Achieving treatment targets after 6 months was associated with lower rates of pain, disability, presenteeism and absenteeism, which reflected improved quality of life. Provider views on adherence appeared discordant with patient claims, and did not predict target achievement. Never smoking, lower body mass index, and lower prednisone dose (<7.5 mg daily) were independently associated with a higher likelihood of achieving T2T therapeutic goals after 6 months. CONCLUSIONS: A combination of clinical characteristics and provider treatment decisions shapes the "profile" of a patient failing to achieve T2T goals. Low­dose steroid equivalent, never smoking, and lower body mass index appear as individual characteristics independently associated with achieving LDA / remission at 3 and 6 months.

Real-World Data from a Multi-Center Study: Insights to Psoriatic Arthritis Care.

INTRODUCTION: Real-world data indicate disparities in biologic access across Europe. OBJECTIVES: To describe the national structure of PsA care in Poland, with a particular focus on the population of inadequate responders (IRs) and difficulties associated with biologic therapy access. METHODS: A pool of rheumatologic and dermatologic care centers was created based on National Health Fund contract lists (n = 841), from which 29 rheumatologic and 10 dermatologic centers were sampled randomly and successfully met the inclusion criterium. Additionally, 33 tertiary care centers were recruited. For successful center recruitment, one provider had to recruit at least one patient that met the criteria for one of the four pre-defined clinical subgroups, in which all patients had to have active PsA and IR status to at least 2 conventional synthetic disease-modifying drugs (csDMARDs). Self-assessment questionnaires were distributed among physicians and their patients. RESULTS: Barriers to biologic DMARD (bDMARD) treatment are complex and include stringency of reimbursement criteria, health care system, logistic/organizational, and personal choice factors. For patients who are currently bDMARD users, the median waiting time from the visit, at which the reimbursement procedure was initiated, to the first day of bDMARD admission was 9 weeks (range 2-212; 32% < 4 weeks, 29% 5-12 weeks, 26% 13-28 weeks, 13% with >28 weeks delay). Out of all inadequate responder groups, bDMARD users are the only group with "good" therapeutic situation and satisfaction with therapy. Patient satisfaction with therapy is not always concordant with physician assessment of therapeutic status. CONCLUSIONS: Despite the fact that over a decade has passed since the introduction of biologic agents, in medium welfare countries such as Poland, considerable healthcare system barriers to biologic access are present. Out of different IR populations, patient satisfaction with treatment is often discordant with physician assessment of disease status.

Comorbidity burden and clinical characteristics of patients with difficult-to-control rheumatoid arthritis.

INTRODUCTION: Difficult-to-treat rheumatoid arthritis (RA) is a significant clinical problem despite no clear definition. We aimed to provide clinical characteristics and associated comorbidities of RA patients in relation to disease control. METHODS: RA characteristics and physician-recorded comorbidities were analyzed in a sample of 1937 RA patients. Patients treated for RA for 5.2 y (IQR, 2.1-11.3) were classified as difficult-to-control when presenting with DAS28-ESR > 3.2 despite previous use of at least 2 csDMARDs. A comparison of demographic and RA-related characteristics between difficult-to-treat and low disease activity patients (DAS28-ESR ≤ 3.2) was performed. Comorbidity burden was assessed by calculating Rheumatic Diseases Comorbidity Index (RDCI). Logistic regression model was constructed for difficult-to-control disease. RESULTS: Hypertension (46.9% (95%CI, 44.7-49.2)), coronary artery disease (CAD) (18.5% (95%CI, 16.8-20.3)), and diabetes (14.4% (95%CI, 12.9-16.0)) were the most prevalent conditions in RA patients. When compared with the adequate control group, difficult-to-control patients were increasingly burdened with hypertension (52.7% (95%CI, 47.5-57.8) vs. 42.0% (95%CI, 36.6-47.6); p = 0.006), cardiovascular diseases (24.2% (95%CI, 20.1-28.9) vs. 11.1% (95%CI, 8.0-15.1); p < 0.001), respiratory system diseases (7.0% (95%CI, 4.8-10.2) vs. 3.3% (95%CI, 1.8-5.9); p = 0.03) and gastroduodenal ulcers (2.3% (95%CI, 1.2-4.4) vs. 0.3% (95%CI, 0.1-1.8); p = 0.04). Patients with higher RDCI had lower chance to obtain low disease activity (OR 0.69 (95%CI, 0.61-0.79); p < 0.001). In multivariate analysis, RDCI was independently associated with difficult-to-control disease (OR 1.46 (95%CI, 1.21-1.76); p < 0.001). CONCLUSIONS: RA patients suffer from a variety of comorbidities. Cardiovascular and respiratory system diseases occur twice as often in difficult-to-control patients. RDCI may provide a valuable tool in evaluating a risk for difficult-to-control RA. Key Points • Hypertension, coronary artery disease and diabetes are the most prevalent comorbidities in rheumatoid arthritis. • Cardiovascular and respiratory tract diseases as well as gastroduodenal ulcers are more common among difficult-to-control patients, when compared with subjects with adequately controlled RA. • Rheumatic Diseases Comorbidity Index is an independent predictor for difficult-to-control RA.

Prevalence and clinical characteristics of rheumatoid arthritis in Poland: a nationwide study.

INTRODUCTION: There are no reliable data regarding the prevalence of rheumatoid arthritis (RA) in Poland. MATERIAL AND METHODS: The first stage was a face-to-face survey on a nationwide representative sample of 3000 people, which identified respondents with a physician-confirmed diagnosis of RA. The second stage was a survey of RA patients, which characterized the disease course and treatment. It was evaluated by analysis of a representative group of 1957 RA patients in routine clinical practice. RESULTS: The overall RA prevalence in Poland was 0.9% (95% CI: 0.6-1.2%), 1.06% for women, 0.74% for men. Seventy-eight percent were female, mean age was 56 and mean disease duration 7 years. Younger patients (< 50) remained professionally active in 90% of cases. Thirty percent of patients were diagnosed within 3 months of the first RA symptoms, while for 17% it took more than 1 year. Fifty-six percent of newly diagnosed patients were characterized by high disease activity (DAS-28 > 5.1). Presently, low disease activity (DAS-28 < 3.2) was found in 38.5% of patients. In Poland, 94% of patients have been treated with non-steroid anti-inflammatory drugs, almost 80% with glucocorticoids. Meanwhile, methotrexate, as an anchor drug in Poland, has been used by 80% of patients, biological agents by 2.94% of patients. CONCLUSIONS: This is the first cross-sectional population-based epidemiological study regarding prevalence of RA in the adult Polish population. The results demonstrate a high prevalence, falling within the upper boundary estimates for Europe. Despite ongoing treatment, the majority still have moderate to high disease activity, and the use of biological therapies is low.

Tofacitinib in the treatment of patients with rheumatoid arthritis: position statement of experts of the Polish Society for Rheumatology.

Tofacitinib is a newly approved small-molecule targeted synthetic disease-modifying antirheumatic drug. The drug was designed as a selective and specific inhibitor of pro-inflammatory receptor signalling. Tofacitinib inhibits the process of intracellular signalling from the receptor to the cellular nucleus and inhibits the inflammation process via a new pathway (inhibition of the Janus kinases), which is unavailable to biological medicines. Tofacitinib has been approved for use in the treatment of patients with moderate to severe active RA. The drug may be used in combination with methotrexate or another conventional synthetic disease-modifying antirheumatic drug or in monotherapy. The efficacy of tofacitinib has been confirmed in several clinical trials. The drug inhibits radiographic progression of the disease. The innovative mechanism of action of tofacitinib is a noteworthy feature because it offers hope of effective treatment for patients who fail to respond to other drugs. The presented article discusses the mechanism of action and the clinical application of tofacitinib. Tofacitinib represents a new group of disease-modifying antirheumatic drugs that can be placed on an equal footing with biological drugs already available.

Methotrexate treatment for rheumatoid arthritis in Poland: Retrospective analysis of patients in routine clinical practice.

OBJECTIVES: The aim of this study was to evaluate methotrexate (MTX) treatment administered by Polish rheumatologists in everyday practice. MATERIAL AND METHODS: The study was based on a retrospective analysis of a cohort of 1957 patients with rheumatoid arthritis (RA). It was conducted among 100 rheumatologists, each of whom received 20 questionnaires and completed them based on the data from their rheumatoid arthritis patients. RESULTS: Methotrexate was taken by 91% of patients, and 80% of them continued the treatment either as a monotherapy (65%) or concomitantly with other disease-modifying anti-rheumatic drugs. In 60% of the cases, therapy was initiated within six months of diagnosis. Dose modifications were observed in 76% of cases and were contingent on different factors, e.g. lack of efficacy, presence of adverse events. The most prevalent adverse events were nausea and vomiting, weakness, and elevated liver enzyme activity. The most common initial dose of MTX was 10 or 15 mg/week. An increase in dose to the maximum of 25 mg/week was observed in 36% of cases, with continuation for 27% of patients. Treatment interruption was noted in 21% of patients, predominantly due to MTX intolerance; however, in 13% of cases, it was due to patient choice. CONCLUSIONS: Methotrexate is the most common agent used to treat rheumatoid arthritis. Dose modifications are often applied to maximise efficacy and reduce adverse reactions, which could lead to withdrawal. Methotrexate is an effective drug for treatment of RA when used according to current recommendations. To optimise MTX therapy, regular medical visits are required.

[Bisphosphonates in the treatment of multiple myeloma]. / Bifosfoniany w leczeniu szpiczaka mnogiego.

Bisphosphonates are the most potent class of antiresorpitve drugs used in the treatment of bone diseases with enhanced resorption, like malignant osteolysis, osteoporosis and Paget's disease. Multiple myeloma is commonly associated with skeletal morbidity, including osteolysis, bone fractures, pain and hypercalcemia. These clinical complications result from increased osteoclast number and function which is due to release of osteoclast-stimulating factors by myeloma cells and the tumoral environment. By inhibition of osteoclast activity and inducing cell apoptosis, bisphosphonates can prevent development of bone destruction in myeloma patients. This article reviews efficacy of bisphosphonates in reducing skeletal events in patients with multiple myeloma and several in vitro studies which have shown that aminobisphosphonates may act as antimyeloma agents.