Trial of Upadacitinib and Adalimumab for Psoriatic Arthritis.

BACKGROUND: The Janus kinase inhibitor upadacitinib is a potential treatment for psoriatic arthritis. The efficacy and safety of upadacitinib as compared with adalimumab, a tumor necrosis factor α inhibitor, in patients who have an inadequate response to nonbiologic disease-modifying antirheumatic drugs are unclear. METHODS: In a 24-week, phase 3 trial, we randomly assigned patients in a 1:1:1:1 ratio to receive oral upadacitinib at a dose of 15 mg or 30 mg once daily, placebo, or subcutaneous adalimumab (40 mg every other week). The primary end point was an American College of Rheumatology 20 (ACR20) response (≥20% decrease in the number of tender and swollen joints and ≥20% improvement in at least three of five other domains) at week 12 with upadacitinib as compared with placebo. Secondary end points included comparisons of upadacitinib with adalimumab. RESULTS: A total of 1704 patients received an active drug or placebo. The percentage of patients who had an ACR20 response at week 12 was 70.6% with 15-mg upadacitinib, 78.5% with 30-mg upadacitinib, 36.2% with placebo (P<0.001 for both upadacitinib doses vs. placebo), and 65.0% with adalimumab. The difference between groups for 15-mg upadacitinib as compared with adalimumab was 5.6 percentage points (95% confidence interval [CI], -0.6 to 11.8) and for 30-mg upadacitinib as compared with adalimumab was 13.5 percentage points (95% CI, 7.5 to 19.4). Both upadacitinib doses were noninferior to adalimumab for the ACR20 response at week 12; the 30-mg dose but not the 15-mg dose was superior to adalimumab. The incidence of adverse events through week 24 was 66.9% with 15-mg upadacitinib, 72.3% with 30-mg upadacitinib, 59.6% with placebo, and 64.8% with adalimumab. There were serious infections in 1.2%, 2.6%, 0.9%, and 0.7% of the patients, respectively. Hepatic disorders occurred in 9.1% of patients in the 15-mg upadacitinib group and 12.3% in the 30-mg upadacitinib group, but grade 3 increases in aminotransferase levels occurred in 2% of patients or fewer in all groups. CONCLUSIONS: The percentage of patients with psoriatic arthritis who had an ACR20 response at week 12 was significantly higher with 15-mg or 30-mg upadacitinib than with placebo. The 30-mg dose but not the 15-mg dose was superior to adalimumab. Adverse events were more frequent with upadacitinib than with placebo. (Funded by AbbVie; SELECT-PsA 1 ClinicalTrials.gov number, NCT03104400.).

Association of MICA and NKG2D genetic variants with disease susceptibility and outcome of anti-TNF therapy in patients with axial spondyloarthritis.

OBJECTIVES: The disruption of the NKG2D-MICA axis can induce an enhanced immune response and promote autoimmune processes during axial spondyloarthritis (axSpA) pathogenesis. We aimed to investigate potential relationships between selected single nucleotide polymorphisms within the MICA and NKG2D genes and disease susceptibility and clinical parameters in axSpA patients treated with TNF inhibitors. METHODS: Genotyping of MICA rs1051792 and NKG2D rs1154831, rs1049174, and rs2255336 was performed in 163 axSpA patients and 234 healthy controls using a real-time PCR method. RESULTS: MICA rs1051792 A allele was more common in patients than in controls (p<0.0001). Patients with the AA genotype showed greater disease activity score (BASDAI) after three (p=4×10-4) and six (p=0.032) months of treatment compared to G carriers. After three months of therapy with anti-TNFs, the MICA AA homozygosity occurred more often in non-responsive or moderately responsive patients than good responders with the same genotype (p=1×10-4). Additionally, patients bearing the NKG2D rs1154831 CC genotype demonstrated lower BASDAI scores (p=0.035) and were significantly more common among subjects with a good outcome (p=0.004) after six months of treatment. CONCLUSIONS: These results suggest that MICA and NKG2D gene polymorphisms may be biomarkers associated with disease susceptibility and clinical outcomes after anti-TNF therapy in axSpA patients and imply a rather less favourable effect of the MICA A and NKG2D G genetic variants.

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.

Effects of filgotinib on semen parameters and sex hormones in male patients with inflammatory diseases: results from the phase 2, randomised, double-blind, placebo-controlled MANTA and MANTA-RAy studies.

OBJECTIVES: The phase 2 MANTA and MANTA-RAy studies aimed to determine if the oral Janus kinase 1 preferential inhibitor filgotinib affects semen parameters and sex hormones in men with inflammatory diseases. METHODS: MANTA (NCT03201445) and MANTA-RAy (NCT03926195) included men (21-65 years) with active inflammatory bowel disease (IBD) and rheumatic diseases (rheumatoid arthritis, spondyloarthritis or psoriatic arthritis), respectively. Eligible participants had semen parameters in the normal range per the WHO definition. In each study, participants were randomised 1:1 to receive once-daily, double-blind filgotinib 200 mg or placebo for 13 weeks for pooled analysis of the primary endpoint (proportion of participants with a ≥50% decrease from baseline in sperm concentration at week 13). Participants who met the primary endpoint were monitored over an additional 52 weeks for 'reversibility'. Secondary endpoints included change from baseline to week 13 in: sperm concentration, total motility, normal morphology, total count and ejaculate volume. Sex hormones (luteinising hormone, follicle stimulating hormone, inhibin B and total testosterone) and reversibility were exploratory endpoints. RESULTS: Across both studies, 631 patients were screened, and 248 were randomised to filgotinib 200 mg or placebo. Baseline demographics and characteristics were similar within indications between treatment groups. Numerically similar proportions of filgotinib-treated versus placebo-treated patients met the primary endpoint (8/120 (6.7%) vs 10/120 (8.3%)), Δ-1.7% (95% CI -9.3% to 5.8%)). There were no clinically relevant changes from baseline to week 13 in semen parameters or sex hormones, or patterns of reversibility between treatment groups. Filgotinib was well tolerated, with no new safety events. CONCLUSIONS: Results suggest that once daily filgotinib 200 mg for 13 weeks has no measurable impact on semen parameters or sex hormones in men with active IBD or inflammatory rheumatic diseases.

Efficacy and safety of switching from reference adalimumab to CT-P17 (100 mg/ml): 52-week randomized, double-blind study in rheumatoid arthritis.

OBJECTIVE: To compare the safety and efficacy of switching from reference adalimumab to adalimumab biosimilar CT-P17 with continuing reference adalimumab/CT-P17 in active RA. METHODS: This double-blind, phase III study randomized (1:1) subjects with active RA to receive 40 mg (100 mg/ml) CT-P17 or European Union-sourced reference adalimumab subcutaneously every 2 weeks (Q2W) until week (W) 24 [treatment period (TP) 1]. Thereafter, subjects receiving reference adalimumab were randomized (1:1) to continue reference adalimumab or switch to CT-P17 from W26 (both Q2W until W48; TP2). Subjects receiving CT-P17 in TP1 continued CT-P17. W0-W24 results were previously reported; we present W26-W52 findings. End points were efficacy (including joint damage progression), pharmacokinetics, safety and immunogenicity. RESULTS: Of 607 subjects who initiated TP2 treatment, 303 continued CT-P17, 153 continued reference adalimumab and 151 switched to CT-P17. Efficacy improvements up to W24 were maintained during TP2; efficacy was comparable among groups. At W52, 20% improvement in ACR response rates were 80.5% (continued CT-P17), 77.8% (continued reference adalimumab) and 82.2% (switched to CT-P17). Joint damage progression was minimal. Mean trough serum adalimumab concentrations were similar among groups. CT-P17 and reference adalimumab safety profiles were numerically similar and switching did not affect immunogenicity. At W52, 28.4% (continued CT-P17), 27.0% (continued reference adalimumab) and 28.3% (switched to CT-P17) of subjects were anti-drug antibody-positive. CONCLUSION: Efficacy, pharmacokinetics, safety and immunogenicity of CT-P17 and reference adalimumab were comparable after 1 year of treatment, including after switching from reference adalimumab to CT-P17. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT03789292.

Th2 Cytokines (Interleukin-5 and -9) Polymorphism Affects the Response to Anti-TNF Treatment in Polish Patients with Ankylosing Spondylitis.

Ankylosing spondylitis (AS) is an inflammatory disease that belongs to the spondyloarthritis family. IL-5 and IL-9 belong to the group of Th2 cytokines of anti-inflammatory nature. Polymorphisms in their coding genes have been so far associated with various inflammatory diseases, but there are no reports regarding their involvement in AS pathogenesis to date. The purpose of the study was to investigate relationships between IL5 and IL9 genetic variants with AS susceptibility, clinical parameters as well as response to therapy with TNF inhibitors. In total 170 patients receiving anti-TNF therapy and 218 healthy controls were enrolled in the study. The genotyping of IL5 rs2069812 (A > G) and IL9 rs2069885 (G > A) single nucleotide polymorphisms was performed using the Real-Time PCR method based on LightSNiP kits assays. The present study demonstrated significant relationships between IL5 rs2069812 and IL9 rs2069885 polymorphisms and response to anti-TNF therapy. Presence of the IL5 rs2069812 A allele in patients positively correlated with better response to treatment (p = 0.022). With regard to IL9 rs2069885, patients carrying the A allele displayed better outcomes in anti-TNF therapy (p = 0.046). In addition, IL5 rs2069812 A and IL9 rs2069885 A alleles were associated with lower CRP and VAS values. The obtained results may indicate a significant role for IL-5 and IL-9 in the course of AS and response to anti-TNF therapy.

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.

Secukinumab in patients with psoriatic arthritis and axial manifestations: results from the double-blind, randomised, phase 3 MAXIMISE trial.

OBJECTIVES: MAXIMISE (Managing AXIal Manifestations in psorIatic arthritis with SEcukinumab) trial was designed to evaluate the efficacy of secukinumab in the management of axial manifestations of psoriatic arthritis (PsA). METHODS: This phase 3b, double-blind, placebo-controlled, multi-centre 52-week trial included patients (≥18 years) diagnosed with PsA and classified by ClASsification criteria for Psoriatic Arthritis (CASPAR) criteria, with spinal pain Visual Analogue Score ≥40/100 and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥4 despite use of at least two non-steroidal anti-inflammatory drugs (NSAIDs). Patients were randomised (1:1:1) to secukinumab 300 mg, secukinumab 150 mg or placebo weekly for 4 weeks and every 4 weeks thereafter. At week 12, placebo patients were re-randomised to secukinumab 300/150 mg. Primary endpoint was ASAS20 (Assessment of SpondyloArthritis international Society) response with secukinumab 300 mg at week 12. RESULTS: Patients were randomly assigned; 167 to secukinumab 300 mg, 165 to secukinumab 150 mg and 166 to placebo. Secukinumab 300 mg and 150 mg significantly improved ASAS20 response versus placebo at week 12 (63% and 66% vs 31% placebo). The OR (95% CI) comparing secukinumab 300 mg and 150 mg versus placebo, using a logistic regression model after multiple imputation, was 3.8 (2.4 and 6.1) and 4.4 (2.7 and 7.0; p<0.0001). CONCLUSIONS: Secukinumab 300 mg and 150 mg provided significant improvement in signs and symptoms of axial disease compared with placebo in patients with PsA and axial manifestations with inadequate response to NSAIDs. TRIAL REGISTRATION NUMBER: NCT02721966.

Polymorphisms within Genes Coding for IL-17A and F and Their Receptor as Clinical Hallmarks in Ankylosing Spondylitis.

IL-17A and IL-17F together with their coreceptor (IL-17RA/RC) were reported to play a significant role in the pathogenesis of spondyloarthritis. The group of axial spondyloarthritis comprises ankylosing spondylitis (AS), a rheumatic disease characterized by chronic inflammation of the joints in the spine. This study is aimed at investigating IL-17A, IL-17F, IL-17RA, and IL-17RC polymorphisms as potential biomarkers of disease susceptibility, clinical parameters, and anti-TNF treatment outcome in a cohort of Polish ankylosing spondylitis patients. In total, 328 subjects, including 138 AS patients and 190 healthy volunteers, participated in the study. Genotyping of IL-17A rs2275913 (G/A), IL-17F rs763780 (A/G), IL-17RA rs4819554 (A/G), and IL-17RC rs708567 (G/A) was performed on real-time PCR instrument using LightSNiP assays. No significant differences were revealed in genotype and allele distribution between patients and controls despite the association of the IL-17RC rs708567 AA homozygosity with the earlier onset of the disease. Moreover, some relationships between IL-17F rs763780 and IL-17RA rs4819554 polymorphisms with clinical parameters related to the disease activity and anti-TNF treatment outcome were observed. IL-17F rs763780 G allele was found to be associated with high disease activity and BASDAI after 6 months and poor response to the treatment while higher VAS values were more common among IL-17RA rs4819554 G variant carriers. In conclusion, the IL-17F rs763780 polymorphism should be considered as a promising biomarker of disease activity and anti-TNF treatment outcome. The IL-17RA rs48419554 G allele may serve as a potential marker of disease severity in Polish AS patients.

The Effect of Platelet-Rich Plasma on the Intra-Articular Microenvironment in Knee Osteoarthritis.

Knee osteoarthritis (KOA) represents a clinical challenge due to poor potential for spontaneous healing of cartilage lesions. Several treatment options are available for KOA, including oral nonsteroidal anti-inflammatory drugs, physical therapy, braces, activity modification, and finally operative treatment. Intra-articular (IA) injections are usually used when the non-operative treatment is not effective, and when the surgery is not yet indicated. More and more studies suggesting that IA injections are as or even more efficient and safe than NSAIDs. Recently, research to improve intra-articular homeostasis has focused on biologic adjuncts, such as platelet-rich plasma (PRP). The catabolic and inflammatory intra-articular processes that exists in knee osteoarthritis (KOA) may be influenced by the administration of PRP and its derivatives. PRP can induce a regenerative response and lead to the improvement of metabolic functions of damaged structures. However, the positive effect on chondrogenesis and proliferation of mesenchymal stem cells (MSC) is still highly controversial. Recommendations from in vitro and animal research often lead to different clinical outcomes because it is difficult to translate non-clinical study outcomes and methodology recommendations to human clinical treatment protocols. In recent years, significant progress has been made in understanding the mechanism of PRP action. In this review, we will discuss mechanisms related to inflammation and chondrogenesis in cartilage repair and regenerative processes after PRP administration in in vitro and animal studies. Furthermore, we review clinical trials of PRP efficiency in changing the OA biomarkers in knee joint.

Association of MICA-129Met/Val polymorphism with clinical outcome of anti-TNF therapy and MICA serum levels in patients with rheumatoid arthritis.

MHC class I polypeptide-related sequence A (MICA) is a stress-induced protein involved in activation of NK and T cells through interaction with NKG2D receptor. These molecules are atypically expressed in synovium of patients diagnosed with rheumatoid arthritis (RA). A total of 279 patients with RA, qualified to TNF-blockade therapy, were genotyped for MICA rs1051792 SNP. The effectiveness of anti-TNF agents was assessed with European League Against Rheumatism criteria. Significant relationship between MICA rs1051792 and outcome of TNF-blockade therapy has been found. The MICA rs1051792 GG genotype was overrepresented in patients non-responsive to anti-TNF drugs in comparison with other genotypes (p = 0.010). On the other hand, beneficial therapeutic response was more frequently detected among RA subjects possessing heterozygous genotype than those with homozygous genotypes (p = 0.003). Furthermore, increased MICA concentrations in serum were observed in patients possessing MICA rs1051792 GG genotype as compared with those with GA or AA genotypes (p = 1.8 × 10-5). The results from this study indicate the potential influence of MICA rs1051792 polymorphism on modulation of therapeutic response to TNF-blockade treatment in RA.

The changing role of ultrasonography examination in patients with rheumatoid arthritis in light of recent studies.

For many years, ultrasonography (US) has been a widely accepted modality used for joint assessment in patients with rheumatoid arthritis (RA). Given the efficacy of present day therapies, there is scepticism whether it is required in the first place. The most recent clinical Targeting synovitis in Early Rheumatoid Arthritis (TaSER) and Clinical Tight Control Therapy (ARCTIC) trials' results appear to contradict it, yet this does not necessarily mean ultrasound has no place in modern rheumatology. The possibility of detecting inflammation at a subclinical level carries a tremendous predictive value, enabling identification of patients likely to experience an exacerbation in the coming months. Therefore, US should be a part of the decision-making process regarding treatment modification or introduction of any additional interventions, such as glucocorticosteroid injections. The results of the most recent clinical trials do not negate the usefulness of US, but merely suggest that it ought to be used in moderation.

The exposure to biologic and targeted synthetic disease-modifying antirheumatic drugs in pregnancy and lactation.

Chronic inflammatory diseases often affect women of childbearing age. Since biologic and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs) are more available, their use during conception, pregnancy and lactation has become a matter of concern. Current studies prove the safety of innovative therapy in pregnant women and may contribute to its wider use than before in pregnancy and lactation. It mainly concerns tumour necrosis factor α (TNF-α) inhibitors. We searched PubMed using Medical Subject Headings (MeSH) terms and identified relevant studies and guidelines. We present up-to-date knowledge of bDMARDs and tsDMARDs safety in pregnant and breastfeeding women.

Efficacy and safety of switching from rituximab to biosimilar CT-P10 in rheumatoid arthritis: 72-week data from a randomized Phase 3 trial.

OBJECTIVE: To evaluate the efficacy and safety of CT-P10, a rituximab biosimilar after a single switch, during a multinational, randomized, double-blind Phase 3 trial involving patients with RA. METHODS: Patients received 48 weeks' treatment with CT-P10 or United States- or European Union-sourced reference rituximab (US-RTX and EU-RTX, respectively). Patients entering the extension period (weeks 48-72) remained on CT-P10 (CT-P10/CT-P10; n = 122) or US-RTX (US-RTX/US-RTX; n = 64), or switched to CT-P10 from US-RTX (US-RTX/CT-P10; n = 62) or EU-RTX (EU-RTX/CT-P10; n = 47) for an additional course. Efficacy endpoints included Disease Activity Score using 28 joints (DAS28), American College of Rheumatology (ACR) response rates, and quality of life-related parameters. Pharmacodynamics, immunogenicity and safety were also assessed. RESULTS: At week 72, similar improvements were observed by disease activity parameters including DAS28 and ACR response rate in the four extension period treatment groups. Quality of life improvements at week 72 vs baseline were similarly shown during the extension period in all groups. Newly developed anti-drug antibodies were detected in two patients following study drug infusion in the extension period. Similar pharmacodynamic and safety profiles were observed across groups. CONCLUSION: Long-term use of CT-P10 up to 72 weeks was effective and well tolerated. Furthermore, switching from reference rituximab to CT-P10 in RA was well tolerated and did not result in any clinically meaningful differences in terms of efficacy, pharmacodynamics, immunogenicity and safety. TRAIL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT02149121.

Factors associated with quality of life in systemic sclerosis: a cross-sectional study.

INTRODUCTION: Systemic sclerosis (SSc) is a connective tissue disease characterized by progressive fibrosis of the skin and internal organs, leading to their failure and disturbances in the morphology and function of blood vessels. The disease affects people in different ways, and identifying how the difficulties and limitations are related to quality of life may contribute to designing helpful interventions. The aim of this study was to identify factors associated with quality of life in people with SSc. METHODS: This was a cross-sectional study conducted in 11 rheumatic centres in Poland. Patients diagnosed with SSc were included. Quality of life was measured using the SSc Quality of Life Questionnaire (SScQoL). The following candidate factors were entered in preliminary multivariable analysis: age, place of residence, marital status, occupational status, disease type, disease duration, pain, fatigue, intestinal problems, breathing problems, Raynaud's symptoms, finger ulcerations, disease severity, functional disability, anxiety and depression. Factors that achieved statistical significance at the 10% level were then entered into a final multivariable model. Factors achieving statistical significance at the 5% level in the final model were considered to be associated with quality of life in SSc. RESULTS: In total, 231 participants were included. Mean age (SD) was 55.82 (12.55) years, disease duration 8.39 (8.18) years and 198 (85.7%) were women. Factors associated with quality of life in SSc were functional disability (ß = 2.854, p < 0.001) and anxiety (ß = 0.404, p < 0.001). This model with two factors (functional disability and anxiety) explained 56.7% of the variance in patients with diffuse SSc and 73.2% in those with localized SSc. CONCLUSIONS: Functional disability and anxiety are significantly associated with quality of life in SSc. Interventions aimed at improving either of these factors may contribute towards improving the quality of life of people with SSc.

The rheumatoid hand in the light of fluorescence: a diagnostic technique of the future?

Fluorescence spectroscopy is usually applied in physics, chemistry and related sciences. However, in recent years we can observe a growing interest in fluorescence spectroscopy for medical diagnostics. Currently, it is beginning to be used in the monitoring of rheumatoid arthritis (RA) activity. As the knowledge on RA increases, growing importance is being placed on the evaluation of synovitis. Today, it is difficult to imagine contemporary rheumatology without ultrasound (US) and magnetic resonance imaging (MRI). However, it turns out that these are not the only methods allowing one to visualise subclinical lesions, particularly synovitis. Fluorescence optical imaging (FOI) is also useful for the evaluation of inflammatory lesions in the joints. In the future, FOI may become competitive with "traditional" imaging studies. It is characterised by low cost, short duration and similar sensitivity to US.

Determination of antibodies in everyday rheumatological practice.

Antibody determination is routinely used in everyday rheumatological practice. Its result repeatedly determines the diagnosis or exclusion of a particular disease. Antibodies are immunoglobulins, i.e. some of the most important proteins in the immune system, and have specific properties that we should know. In addition, there are a number of factors that can affect their concentration, including drugs commonly used in the treatment of rheumatic diseases. There are definite indications, when the total concentrations of individual classes of immunoglobulins should be initially determined and it should be evaluated whether the patient produces them at all or their production is impaired. In some cases, we should evaluate the levels of specific antibodies along with the total protein concentration and the γ-globulin fraction, in which the antibodies are contained. The article presents information on the most common mistakes made when performing these tests.

Pharmacoeconomic evaluation of treatment effectiveness with selected biologic treatment in rheumatoid arthritis therapy.

OBJECTIVES: Modern treatment of autoimmune diseases is becoming increasingly widely used. We owe it to the continuous and rapid development of biotechnology, molecular biology, immunology, and biochemistry. The proven effectiveness of biological therapy in rheumatoid arthritis (RA) should result in its widespread use. At present, only about 1% of patients with RA have access to biological therapy in Poland. MATERIAL AND METHODS: The study material was retrospectively collected in the Rheumatology and Systemic Tissue Diseases Clinic and Rheumatology Outpatient Clinic in dr Jan Biziel University Hospital No. 2 in Bydgoszcz 2009-2014. Patients were divided into 3 groups: patient receiving infliximab, etanercept and adalimumab. RESULTS: The study involved analyses of cost effectiveness. The time horizon of patient documentation analysis ranged from the time a patient was enrolled to infliximab, etanercept or adalimumab therapy until remission of the disease. The majority of patients achieved remission in the case of adalimumab treatment (85.29%), followed by etanercept (74.07%), then infliximab (37.21%). Taking into account the DAS28 parameter, analysis was performed using medical costs of the analyzed treatment regimens. For this purpose, the incremental cost-effectiveness ratio (ICER) was calculated. According to the analysis, obtaining one DAS28 unit, replacing infliximab with etanercept, would cost PLN 40 964 67. Higher costs would be required in the case of replacement of infliximab with adalimumab - PLN 43 076 08. Obtaining one additional DAS28 unit (in this case, a decrease in DAS28 by one unit) by introducing adalimumab instead of etanercept would amount to PLN 45 409 74. CONCLUSIONS: Undoubtedly, the pharmacoeconomic analysis makes it easier to decide on the appropriate treatment. Therefore, its implementation should be a widely used solution not only for RA, but also for other diseases. Health care and other entities' systems should also be improved in such a way that the data needed for pharmacoeconomic analysis are fully available.

Pharmacoeconomic evaluation of costs of rheumatoid arthritis therapy with selected biological treatment.

OBJECTIVES: Among autoimmune diseases, rheumatoid arthritis (RA) is the most common chronic inflammatory disease of the joints. Its pathogenesis is still not fully understood, but the gained knowledge has contributed to the development of modern treatment. The introduction of biological therapy for RA has been a breakthrough in the standard approach to the treatment of this disease. MATERIAL AND METHODS: The study material was retrospectively collected in the Rheumatology and Systemic Tissue Diseases Clinic and Rheumatology Outpatient Clinic in dr. Jan Biziel University Hospital No. 2 in Bydgoszcz. Patients were divided into 3 groups: patients receiving infliximab - 43 patients, etanercept - 27 patients and adalimumab - 34 patients. In the study, the pharmacoeconomic analysis included direct and indirect medical costs. Direct medical costs analyzed in the study included costs for the purchase of medications, diagnostic and imaging costs, and medical consultations and hospitalization costs. The analysis included all direct medical costs incurred by the hospital and the patient, as well as indirect costs outside the healthcare sector - that is, the Polish Social Insurance Institution benefits (disability benefits, rehabilitation benefits, sickness absences). Direct medical costs are also presented from the perspective of the payer - The Polish National Health Fund - taking into account the cost and percentage share of medical expenses. RESULTS: The analysis concerned resources used since the beginning of treatment with a given biological medication for 24 months or earlier if disease remission occurred.A cost-benefit analysis was carried out in the study using biosimilar medications present on the market in relation to the treatment regimens. Considering the total cost, if only Inflectra were used in therapy, PLN 18 151.98 per patient could be saved, and in the case of Remsima, PLN 16 385.14. In less than 19 months, to use infliximab for 43 patients, PLN 780 475.80 more would have to be spent than in the case of the biosimilar medication Inflectra, and PLN 704 561 in the case of Remsima.The highest total cost is generated by treatment with adalimumab, followed by etanercept, and infliximab. Of the costs analyzed, a significant majority was for biological treatment. CONCLUSIONS: Given the Polish financial conditions, the best solution now is to reduce the prices of biological medications. This is possible through the introduction of biosimilar medications that, when placed on the market, reduce the price of the original medication, as is currently the case with Remicade and Enbrel. The introduction of Inflectra and Remsima, as well as Benepali and Erelzi, has reduced the price base of original medications to similar levels of treatment with biosimilar medications. The wider use of biological treatment would also reduce indirect costs.

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.