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Objectives: Systemic sclerosis (SSc) is a disease with cardiovascular impairment and polymorphisms of the gene coding of angiotensin-converting-enzyme 2 (ACE2) may account for its development. Three single nucleotide polymorphisms of ACE2 (C>G rs879922, G>A rs2285666 and A>G rs1978124) were found to increase the risk for development of arterial hypertension (AH) and cardiovascular (CVS) diseases in different ethnicities. We investigated associations of polymorphisms rs879922, rs2285666 and rs1978124 with the development of SSc., Methods: Genomic DNA was isolated from whole blood. Restriction-fragment-length polymorphism was used for genotyping of rs1978124, while detection of rs879922 and rs2285666 was based on TaqMan SNP Genotyping Assay. Serum level of ACE2 was assayed with commercially available ELISA test., Results: 81 SSc patients (60 women, 21 men) were enrolled. Allele C of rs879922 polymorphism was associated with significantly greater risk for development of AH (OR=2.5, p=0.018), but less frequent joint involvement. A strong tendency to earlier onset of Raynaud's phenomenon and SSc was seen in carriers of allele A of rs2285666 polymorphism. They had lower risk for development of any CVS disease (RR=0.4, p=0.051) and tendency to less frequent gastrointestinal involvement. Women with genotype AG of rs1978124 polymorphism had significantly more frequent digital tip ulcers and lower serum level of ACE2., Conclusions: Polymorphisms of ACE2 may account for the development of AH and CVS disorders in SSc patients. Strong tendencies to more frequent occurrence of disease specific characteristics distinct to macrovascular involvement will require further studies evaluating significance of ACE2 polymorphisms in SSc.

Internal medicine emerged as a new medical specialty in the second half of the 19th century. It was based on a novel diagnostic and therapeutic paradigm, and included pathophysiologic interpretation of physical examination, laboratory tests, and imaging techniques, in contrast with previous descriptive approach to clinical problems. Professor Edward J. Sas-Korczyński in 1891 proposed to organize Polish meetings on internal medicine. The proposal was implemented only in 1906 by Antoni W. Gluziński, a famous Polish internist. Despite obstacles set by the partitioning powers, the Society of Internists of the Polish Lands was founded. The name of the association was changed to the Polish Society of Internal Medicine during the congress held in Vilna (now Vilnius) in 1923, the first one organized in the independent Poland. The journal of the Society, Polish Archives of Internal Medicine, was founded and Antoni W. Gluziński was its first editor-in-chief. Later, the journal was edited by Władysław Janowski, Witold E. Orłowski, Andrzej Biernacki, Tadeusz Orłowski, Artur Czyżyk, and Anetta Undas. Witold E. Orłowski was a father of modern Polish internal medicine, and contributed to the development of its subspecialties and their societies. Most of them had roots in the specialist sections of the Polish Society of Internal Medicine. The journal supported the newly founded societies by publication of issues focused on selected subspecialties. Despite the development of subspecialties, the role of internal medicine as a holistic discipline covering the diagnosis and therapy of many organs does not decrease.

VEXAS syndrome is an adult-onset autoinflammatory disease associated with hematologic symptoms. The disease affects primarily males, and leads to death of a significant proportion of the patients. VEXAS syndrome is caused by a somatic mutation of the UBA1 gene in hematopoietic progenitor cells. The clinical picture of the syndrome consists of a number of organ manifestations including those akin to rheumatic diseases, arthritis, myalgia, vasculitis and chondritis., Competing Interests: The author declares no conflict of interest., (Copyright: © 2023 Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji w Warszawie.)

Competing Interests: Competing interests: None declared.

Objectives: The study aimed to characterise the Polish population of (ANCA)-associated vasculitides (AAV) with respiratory involvement (RI), in comparison to the subgroup without lung manifestations and the other cohorts., Methods: Retrospective analysis of the Polish population of AAV with RI was conducted, based on data from the POLVAS registry. Standard descriptive statistics, χ2 test, and Mann-Whitney U test were used to perform comparisons., Results: Among 461 cases qualified to this study, there were 316 cases with RI (68.5%), 206 with granulomatosis with polyangiitis (GPA) (65.2%), 80 with eosinophilic granulomatosis with polyangiitis (EGPA) (25.3%) and 30 with microscopic polyangiitis (MPA) (9.5%). Proportion of RI in GPA, MPA, and EGPA accounted for 67.8%; 40.0%; 97.6%, respectively. The number of relapses was higher in the RI group (median 1.0 vs. 0.0; p=0.01). In the subgroup of combined GPA and MPA with RI, the trends toward higher proportion of deaths (11.7% vs. 5.7%; p=0.07), relapses requiring hospitalisation (52.2% vs. 42.4%, p=0.07) and relapses requiring admission to the intensive care unit (5.6% vs. 1.4%, p=0.09) were observed, median maximal concentration of CRP was higher (46 vs. 25 mg/l; p=0.01) and more aggressive treatment was administered., Conclusions: Prevalence of RI in the Polish population of AAV is similar to the values reported in the literature, however, the proportion observed in GPA is closer to those presented in Asian than Western European cohorts. RI seems to be associated with a more severe course of disease and its presence prompts more aggressive treatment.

Introduction: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by the presence of proteinase‑3 (PR3) or myeloperoxidase (MPO) ANCA. In over 90% of cases, PR3‑ANCA is associated with granulomatosis with polyangiitis (GPA). However, it is also rarely found in microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). On the other hand, MPO‑ANCA being characteristic of MPA (>90% of cases), is also found in about 40% of EGPA and 5% of GPA patients. On the ground of this overlap, clinical importance of ANCA specificity identification has been questioned., Objectives: In this study, we analyzed the clinical and demographic characteristics of AAV subgroups identified by ANCA serotype., Patients and Methods: We conducted a multicenter study of AAV patients (417 GPA, 106 MPA, 102 EGPA; diagnosed between 1990 and 2016), included in the POLVAS registry. The data were systematically collected according to a standardized protocol., Results: In the ANCA-positive group (anti‑MPO, anti‑PR3) a male-to-female ratio was 1:1, whereas in the ANCA-negative group it was 1:2, regardless of AAV diagnosis. Anti‑MPO antibodies were present in significantly older patients. Patients with MPO+GPA and MPO+EGPA were older than those with corresponding ANCA‑negative GPA and EGPA as well as PR3+AAV. Moreover, ANCA‑negative AAV was characterized by a low risk of end‑stage kidney disease and death., Conclusions: The presence and specificity of ANCA in AAV patients are related to sex and age, determine their organ involvement and influence mortality as previously shown. Patients with MPO‑ANCA-positive AAV constitute a clinically homogeneous group, whereas PR3‑ANCA-positive patients are much more clinically heterogeneous. ANCA-negative AAV patients are characterized by better prognosis. Thus, ANCA identification is an indispensable element and should not be omitted in establishing AAV diagnosis.

Whipple's disease is a rare, chronic, systemic disorder caused by Tropheryma whipplei infection. The most common symptoms are weight loss, arthralgia, diarrhea and abdominal pain. Other organ involvement can also occur in the patients. Joint manifestations may mimic rheumatoid arthritis or spondyloarthritis. Arthalgia, arthritis, spondylodiscitis, bursitis and/or tenosynovitis are seen in the majority of the patients. This explains why some of the symptoms are misdiagnosed as those of rheumatic diseases. Understanding of Whipple's disease is important for differential diagnostics of several rheumatic symptoms., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2021 Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji w Warszawie.)

Systemic connective tissue diseases (CTDs) comprise a large group of diseases that are auto-immune in nature and characterized by the involvement of multiple systems and organs. Pul-monary hypertension (PH) of various etiologies may develop in the course of CTD, including pulmonary arterial hypertension (PAH), PH secondary to the lung disease, postcapillary PH in the course of left heart disease, and chronic thromboembolic pulmonary hypertension (CTEPH). In addition, the different forms of PH may coexist with each other. Among patients with CTD, PAH occurs most commonly in those with systemic sclerosis, where it affects ap-proximately 8%-12% of patients. The prognosis in patients with untreated PAH is very poor. It is particularly important to identify the high-risk CTD-PAH population and to perform effi-cient and accurate diagnostics so that targeted therapy of the pulmonary arteries can be intro-duced. Echocardiography is used to screen for PH, but clinical and echocardiographic suspicion of PH always requires confirmation by right heart catheterization. Confirmation of PAH ena-bles the initiation of life-prolonging pharmacological treatment in this group of patients, which should be administered in referral centers. Drugs available for pharmacological management include endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and prostacyclins.

Coronavirus disease 2019 (COVID‑19) is an infectious disease that became a global health emergency. This review focuses on the aspects of COVID‑19 pertaining to rheumatology, including signs and symptoms akin to those observed in rheumatic disorders, risk of infection or severe course of the disease in patients with a pre‑ existing rheumatic disease and those receiving antirheumatic or immunosuppressive medication, as well as potential use of antirheumatic or anticytokine therapeutic strategies that are already applied in rheumatology (among others, chloroquine, hydroxychloroquine, tocilizumab, and baricitinib) in patients with COVID‑19.

This study was performed to evaluate the effects of 15-month anti-tumor necrosis factor α (anti-TNF-α) therapy on the aggrecan turnover of female rheumatoid arthritis (RA) patients. Serum was obtained from healthy subjects and female RA patients treated with TNF-α inhibitors (TNFαI) in combination with methotrexate. We measured serum levels of aggrecan chondroitin sulfate 846 epitope (CS846), aggrecan fragments (AGC), disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4) and 5 (ADAMTS-5), as well as their natural inhibitor, known as tissue inhibitor of matrix metalloproteinase-3 (TIMP-3), using immunoassay methods. Serum levels of CS846, AGC, ADAMTS-4, ADAMTS-5 and TIMP-3 were higher in female patients with RA before the treatment in comparison to healthy subjects. Ratio of ADAMTS-5 to TIMP-3 was significantly higher in RA women than in controls, whereas ADAMTS-4/TIMP-3 ratio did not differ from that in controls. During the anti-TNF-α therapy, the serum levels of 846 epitope increased, whereas levels of AGC decreased in female RA patients. Furthermore, 15 months of treatment with TNFαI downregulated serum levels of both ADAMTS, without any effect on TIMP-3 levels. These changes were accompanied by significantly reduced ratios of ADAMTS to TIMP-3. According to our results, anti-TNF-α therapy has a beneficial impact on aggrecan remodeling during RA., Competing Interests: The authors declare that there are no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

The aim of the study was to determine whether plasma levels of total glycosaminoglycans (GAGs), matrix metalloproteinases (MMPs) (MMP-3, MMP-10), and their tissue inhibitors (TIMPs) (TIMP-1, TIMP-2) as well as transforming growth factor β (TGF- β ) differ in the patients with systemic sclerosis (SSc) in relation to the healthy subjects. Plasma samples were obtained from 106 people (64 patients with SSc and 42 healthy individuals) and measured for MMP-3, MMP-10, TIMP-1, TIMP-2, and TGF- β levels using ELISA methods. GAGs isolated from plasma samples were quantified using a hexuronic acid assay. The plasma levels of total GAGs, TIMP-1, TIMP-2, and TGF- β were significantly higher, while MMP-3 was significantly decreased in SSc patients compared to the controls. We have revealed a significant correlation between plasma GAGs and TGF- β ( r = -0.47) and TIMP-2 ( r = 0.38), respectively. The results of this study revealed that remodeling of the extracellular matrix, reflected by quantitative changes in plasma glycosaminoglycans, occurs during systemic sclerosis. Thus, the alterations in GAG metabolism connected with SSc may lead to systemic changes in the properties of the connective tissue extracellular matrix., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Kornelia Kuźnik-Trocha et al.)

Purpose: The aim of this study is to present the treatment modalities and associated side effects in a Polish nation-wide ANCA-associated vasculitides (AAV) patients' cohort., Materials and Methods: Retrospective analysis of patients diagnosed with AAV between 1990 and 2016, included in the POLVAS registry was performed. Standard descriptive statistic methods were used with an emphasis on the treatment modalities., Results: There were 625 patients diagnosed with AAV included in this study: 417 cases of granulomatosis with polyangiitis (GPA; 66.7%), 106 cases of microscopic polyangiitis (MPA; 17.0%) and 102 cases of eosinophilic granulomatosis with polyangiitis (EGPA; 16.3%). The mean age at the date of diagnosis was 50.4 (±15.7) years and the median observational period amounted to 4.0 (2.0-8.0) years. Glucocorticosteroids (GCs) were the medicaments most frequently used for remission induction (593/622; 95.3%), followed by cyclophosphamide (487/622; 78.3%), rituximab (44/622; 7.1%), and methotrexate (39/622; 6.3%). GCs were also most frequently administered for maintenance therapy (499/592; 84.3%), followed by azathioprine (224/592; 37.8%), methotrexate (136/592; 23.0%) and mycophenolate mofetil (99/592; 16.7%). The median cumulative doses of cyclophosphamide and rituximab equalled 7.99 g (4.18-14.0) and 2000 mg (1500-2800), respectively. The most commonly observed adverse events included: infections - 214/551 cases (38.8%), which were associated with the time of observation (OR = 1.05; 95% CI 1.01-1.10), the use of GCs intravenous pulses (OR = 2.76; 95% CI 1.68-4.54) and need for haemodialysis (OR = 1.73; 95% CI 1.10-2.71)., Conclusions: Polish patients with AAV were predominantly treated according to appropriate guidelines. The most frequent adverse events were typical for usually administered immunosuppressive treatment., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Competing Interests: The author declares no conflict of interest.

Sarcoidosis is a systemic multisystem inflammatory disease of unknown etiology. The disease is characterized by formation of non-caseating granulomas. The most common presentation is bilateral hilar lymphadenopathy and lung infiltration, but the disease is very heterogeneous, with an unpredictable clinical course. Musculoskeletal manifestations are common. Bone involvement is less frequent, and usually occurs in patients with chronic multisystem course of the disease. They are most commonly found in the phalanges of hands and feet, and are usually bilateral. The skull, long bones, ribs, pelvis, and axial skeleton may also be affected. Osseous involvement may be asymptomatic but in some cases can cause a severe disability. Imaging techniques are important for diagnosis. Radiological investigations revealed sclerotic or destructive lesions (involving also joints), cystic and punched out lesions and cortical abnormalities. Biopsy is required for differential diagnosis with respect to malignancy. Treatment is a part of systemic therapy and is not needed in all cases. Glucocorticoids and TNF-α antagonists are used for management., Competing Interests: The author declares no conflict of interest., (Copyright © 2020 Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji w Warszawie.)

Systemic sclerosis (SSc) is a rare, chronic autoimmune disease with unknown etiology. Its prominent features are fibrosis, vasculopathy and impaired immune response. Disease can also affect eyes leading to various findings in ophthalmological examination. The objective of this study was to determine the prevalence and type of ocular involvement in patients with SSc. A systematic literature review was conducted using electronic databases. A combination of following keywords was used: "systemic sclerosis" and ophthalmology-related search terms, including the keywords "eye", "ocular" and "ophthalmic". In conclusion, eyelid and conjunctival abnormalities and dry eye disease are among the most common ocular manifestations of SSc. Their diversity is connected to complexity of the disease., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2020 Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji w Warszawie.)

Background: Subcutaneous methotrexate (sMTX) administration is considered more effective than the oral route due to better bioavailability and a lower rate of adverse drug reactions (ADRs); however, clinical data supporting this hypothesis is scarce., Objectives: The aim of the study was to evaluate the efficacy and tolerability of sMTX in patients with active rheumatoid arthritis (RA), including a subset classified as an early stage of RA., Material and Methods: A post-marketing, multicenter, open-label, non-randomized, non-interventional study enrolled 771 adult patients with active RA treated with sMTX (Metex®) for 2-6 weeks. The evaluation of therapy effectiveness (DAS28-ESR or DAS28-CRP) and monitoring of ADRs was an element of routine patient management. Therapy effectiveness was scored as the achievement of remission or response (according to European League Against Rheumatism (EULAR))., Results: Among 761 (98.7%) patients that continued sMTX (after 25-31 weeks), clinical response was achieved by 69.5%, remission by 19.2% and low disease activity by 34.2%. Patients aged >60 years were less likely to achieve both remission (odds ratio (OR) = 0.61 (95% confidence interval (95% CI) = 0.39-0.93)) and clinical response (OR = 0.82 (95% CI = 0.71-0.95)), while overweight/obese patients (OR = 1.11 (95% CI = 1.00-1.24)) and those with early RA had greater chance to reach a clinical response (OR = 1.18 (95% CI = 1.03-1.34)). There were 16 ADRs (no serious or severe). In addition, at least 2-fold increase in alanine transaminase (ALT) activity was noted in 10 patients (1.3%)., Conclusions: After 6-month therapy with sMTX, about 70% of patients with RA achieve a clinical response, and remission was observed in 20%. Younger age, overweight/obesity and an early stage of the disease are factors increasing therapy effectiveness; sMTX is well tolerated.

Osteoarthritis (OA) is characterized by deterioration of the joints and associated with considerable pain and disability. OA is a chronic disease that requires intervention with both non-pharmacological and pharmacological treatment modalities and, inevitably, disease progression may necessitate successive treatments throughout the course of the disease. There is increasing data on the shortfalls of current pharmacological treatment of OA, and safety concerns associated with analgesic therapy use in OA arising from increasing evidence of gastrointestinal, cardiovascular, hepatic and renal adverse events with paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs). Consequently, symptomatic slow-acting drugs for OA (SYSADOAs) may now be considered as a first-line treatment for knee OA, with a particular emphasis placed on the outstanding benefit: risk ratio of pharmaceutical-grade glucosamine and chondroitin sulfate formulations. In this short communication we review recent publications concerned with the safety of paracetamol, NSAIDs and SYSADOAs. Greater understanding of the benefits and limitations of current medications will lead to better disease management in OA. Furthermore, adherence to guideline recommendations across Europe and internationally, such as those from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO), will promote evidence-based medicine and patient-centric care, ultimately leading to greater physician and patient satisfaction.

Background: Sandoz etanercept (SDZ ETN; GP2015) is an etanercept biosimilar with equivalent efficacy and comparable safety and immunogenicity to reference etanercept (ETN) in patients with moderate-to-severe chronic plaque-type psoriasis., Methods: EQUIRA was a phase III, double-blind study conducted in patients with moderate-to-severe rheumatoid arthritis and inadequate response to disease-modifying anti-rheumatic drugs. Eligible patients were randomized 1:1 to receive subcutaneous 50 mg SDZ ETN or ETN, once-weekly, for 24 weeks. At week 24, patients with at least moderate EULAR response in the SDZ ETN group continued SDZ ETN treatment, and those in the ETN group were switched to receive 50 mg SDZ ETN, for up to 48 weeks. Patients received concomitant methotrexate at a stable dose (10-25 mg/week) and folic acid (≥ 5 mg/week). Equivalence between SDZ ETN and ETN for change from baseline in disease activity score including 28 joint count C-reactive protein (DAS28-CRP) at week 24 (primary endpoint) and comparable safety and immunogenicity profile of SDZ ETN and ETN have previously been demonstrated at week 24. Herein, we present the 48-week results of the study after a single switch from ETN to its biosimilar at week 24., Results: The least squares mean (standard error) change in DAS28-CRP from baseline up to week 48 was comparable between "continued SDZ ETN" (- 2.90 [0.12], n = 148) and "switched to SDZ ETN" (- 2.78 [0.13], n = 131) groups. The proportion of patients achieving EULAR good/moderate responses based on DAS28-erythrocyte sedimentation rate and ACR20/50/70 response rates were comparable between the two groups. The proportion of patients with at least one treatment-emergent adverse event was 42.9% in the "continued SDZ ETN" and 38.0% in the "switched to SDZ ETN" groups. Serious adverse events occurred in 4 patients in each of the two groups. After week 24, none of the patients in the switched group developed anti-drug antibodies (ADAs), while 4 patients in the continued SDZ ETN group had single-event, very low titer, non-neutralizing ADAs detected., Conclusions: The 48-week results from the EQUIRA study demonstrate that switch from ETN to SDZ ETN in patients with moderate-to-severe rheumatoid arthritis does not impact the efficacy, safety, or immunogenicity of etanercept., Trial Registration: EudraCT number 2012-002009-23 , Registered 19 April 2012-prospectively registered.

Objectives: Relapsing polychondritis is a rare, multi-systemic and inflammatory condition of unknown origin. We currently lack a core set of measures to assess and follow damage in patients suffering from this condition. Our primary aim was to derive a disease-specific damage measuring tool for relapsing polychondritis, the Relapsing Polychondritis Damage Index (RPDAM)., Methods: We performed an international 4-round multicenter Delphi study during which experts were asked to rate the relevance of potential damage items for relapsing polychondritis (141 items were obtained from a literature review and 12 from expert suggestion), using a Likert Scale. The selection of items for each subsequent round was based on the median rating of each item., Results: Twenty-four experts from 11 nationalities participated in round 1 and 22 in rounds 2, 3 and 4. From the initial 153 potential damage items, 44 items were selected during round 1, 30 items during round 2 and 16 during round 3. During round 4, we refined the index to a total of 17 items referring to ear nose and throat, eye, respiratory, cardiovascular and hematological systems as well as to treatment-related specific damage items., Conclusion: We have developed by international consensus a scoring system to assess damage in patients with relapsing polychondritis. Following its validation, the RPDAM may contribute to improve the care of patients suffering from this rare condition as well as to standardize data collection for future clinical trials., (Copyright © 2018. Published by Elsevier Masson SAS.)

Competing Interests: The author declares no conflict of interest.

Dercum's disease (adiposis dolorosa) is a rare disease of unknown etiology characterized by painful subcutaneous adipose tissue deposits with various localization over the body. The deposits occur histologically as lipomas and are associated with overweight or obesity and a variety of psychiatric disturbances (anxiety, depression, sleep disturbances). Classification of Dercum's disease is related to size and location of adipose nodules (generalized diffuse, generalized nodular, localized nodular and juxta-articular forms). Diagnosis in based on clinical presentation and exclusion of a number of other disorders associated with lipomas. There is no generally accepted management of the patients. Liposuction or lidocaine application has been reported successful in some cases. Other therapeutic methods have been reported but their effectiveness is based on anecdotal descriptions only, and were not confirmed in clinical trials., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2019 Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji w Warszawie.)

Objectives: To demonstrate the equivalent efficacy and compare the safety and immunogenicity of an etanercept biosimilar, GP2015, with reference etanercept (ETN) in patients with moderate-to-severe, active rheumatoid arthritis (RA), characterised by an inadequate response to synthetic or biologic disease-modifying antirheumatic drugs (DMARDs)., Methods: In the EQUIRA study, eligible patients (n=376) were randomised 1: 1 to 50  mg GP2015 or ETN subcutaneously, once weekly, for 24 weeks (treatment period 1). Patients from both groups, with at least moderate European League Against Rheumatism response at week 24, received GP2015 up to week 48 (treatment period 2). All patients continued to receive concomitant methotrexate at a stable dose (10-25  mg/week) until end of the study. The 24-week results are presented here., Results: Equivalent efficacy between GP2015 and ETN was demonstrated if the 95% CI for the difference in disease activity score 28-joint count C reactive protein (DAS28-CRP) change from baseline to week 24 between treatment arms was contained within the prespecified equivalence margin range of -0.6 to 0.6. The least squares mean difference (GP2015-ETN) in change from baseline in DAS28-CRP up to week 24 was -0.07 (95% CI -0.26 to 0.12 [primary endpoint)]. The incidence of treatment-emergent adverse events was comparable between GP2015 (43.5%) and ETN (49.5%). None of the GP2015-treated patients developed neutralising anti-drug antibodies (NAbs) whereas 1.6% and 0.6% of patients in ETN group were NAb positive at weeks 4 and 12, respectively., Conclusion: In patients with RA who had an inadequate response to DMARDs, GP2015 demonstrated a similar efficacy and a comparable safety and immunogenicity profile with ETN., Trial Registration: NCT02638259., Competing Interests: Competing interests: MM-C reports no conflicts of interest. YA reports personal fees from Sandoz, grants and personal fees from Pfizer, grants and personal fees from Roche, during the conduct of the study. AK reports personal fees from Sandoz, outside the submitted work. MHB reports personal fees from Sandoz during the conduct of the study. HS-K reports personal fees from Sandoz/Hexal during the conduct of the study, personal fees from Sandoz/Hexal, grants and personal fees from Novartis, outside the submitted work. EJK reports no conflict of interest. HW, GB, JP and AS are employees of Hexal AG. AD is an employee of Sandoz Inc.

Background: In this study, the effect of 15-month anti-tumor necrosis factor alpha (TNF-α) treatment on circulating levels of plasma sulfated glycosaminoglycans (GAGs) and the nonsulfated GAG hyaluronic acid (HA) in female rheumatoid arthritis (RA) patients was assessed., Methods: Plasma was obtained from healthy subjects and RA women treated with TNF-α antagonists (etanercept or adalimumab or certolizumab pegol) in combination with methotrexate. GAGs were isolated from plasma samples using ion exchange low-pressure liquid chromatography. Total sulfated GAGs were quantified using a hexuronic acid assay. Plasma levels of keratan sulfate (KS) and HA were measured using immunoassay kits., Results: Total sulfated GAGs and HA levels were higher in female RA patients before treatment in comparison to healthy subjects. KS levels did not differ between RA women and controls. Anti-TNF-α treatment resulted in normalization of plasma total GAG and HA levels in RA patients, without any effect on KS levels., Conclusions: Our results suggest that anti-TNF-α therapy has a beneficial effect on extracellular matrix remodeling in the course of RA.

Pulmonary involvement is a severe manifestation of systemic sclerosis (SSc). The study was designed to determine the serum level of surfactant protein D (SP-D) in patients with SSc in relation to clinical and laboratory parameters as well as to analyze dynamics of changes of these indices within one year of observation. SP-D was assayed in 41 patients with SSc and 15 healthy controls. Additionally, pulmonary function tests, chest high-resolution computed tomography (HRCT), and inflammatory markers were assessed. All tests were performed twice: at entry and repeated after one year of observation. The serum level of SP-D was significantly higher in patients with SSc than in healthy controls. Serum concentration of SP-D was significantly higher in patients with systemic sclerosis-related interstitial lung disease (SSc-ILD) than in those without SSc-ILD. SP-D was found to correlate with lung involvement evaluated with the Medsger score (diffusing capacity of the lung for carbon monoxide (DLCO), forced vital capacity, radiological changes, and estimated pressure in the pulmonary artery in echocardiography). SP-D correlated with the honeycombing and/or reticular pattern in HRCT and ground glass opacification pattern. Serum concentration of SP-D was elevated in patients with a decreased DLCO. Furthermore, SP-D was higher in patients with diffuse cutaneous type (dcSSc) of the disease than in those with SSc limited type (lcSSc). Because of the small size of the group, it was not possible to perform a statistical analysis for patients who had different results in HRCT, VC, and Medsger score between the first and the second evaluation. SP-D seems to be an index for assessing lung involvement. It reflects the state of pulmonary fibrosis but not the dynamics of the pulmonary fibrosis progression. Further studies are needed to evaluate clinical application of the index, and currently, there is no evidence for the recommendation of the application of SP-D in routine evaluation of patients with SSc., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Tumour necrosis factor (TNF-α) is one of the main cytokines participating in inflammation and immune response. Biological effects of the cytokine action, mediated by two receptors: TNFRSF1A and TNFRSF1B involve activation of many signal paths, thus change the transcription activity of many genes. The mechanism of action of an anti-TNF medicine consists in blocking TNF-α though preventing activation of signal paths., Aim: To single out mRNA and microRNA genes relating to TNF-α signal paths, the expression of which could indicate sensitivity of cells to the medicine in question., Material and Methods: The material used in the research consisted in the cell line of regular human skin fibroblasts NHDF (CC-2511 Lonza, Basel, Switzerland) exposed to adalimumab with a concentration of 8.00 μg/ml of the medium for 2, 8 and 24 h, compared with the control material, i.e. non-stimulated cells. Molecular analysis was performed using the oligonucleotide expressive micro-matrices technology HG-U133A, miRNA 2.0 Array micro-matrices and RTqPCR., Results: mRNA: BIRC5, MAP3K4, ZFAND5, JUN differentiate cells exposed to the anti-TNF medicine, regardless of the time of cell/medicine incubation. TNF-α transcription activity is reduced during exposure of NHDF cells to adalimumab. miRNA regulating transcription activity of the said 4 mRNA and miRNA related to TNF-α and its receptors was also singled out., Conclusions: It was ascertained that adalimumab has therapeutic potential and affects genes engaged in signal paths activated by TNF-α. The results indicate the TNF-α usefulness as the molecular, supplementary marker in diagnostics and control of treatment effects., Competing Interests: The authors declare no conflict of interest.

Background: Fibulin-3 (Fib-3) is a new potential biomarker of articular cartilage metabolism., Objectives: The aim of the study was to evaluate the effect of anti-TNF therapy on serum fibulin-3, cartilage oligomeric matrix protein (COMP), procollagen II C-propeptide (PIICP), and urinary C-terminal telopeptide of type II collagen (CTX-II) levels in relation to calprotectin (MRP8/14) and disease activity in rheumatoid arthritis patients., Material and Methods: In the study, 35 female patients with rheumatoid arthritis (RA) were investigated. The concentration of fibulin-3, COMP, PIICP, MRP8/14, and urinary CTX-II in serum was measured before and after anti-TNF therapy. Ten healthy women were investigated as the controls., Results: The concentration of fibulin-3 in RA patients before treatment did not differ significantly from the concentration of fibulin-3 in the control group. A significantly higher concentration of fibulin-3 was noted prior to treatment in the group of women with a worse response to the therapy (non-responders) compared to the concentration of fibulin-3 in the healthy women. During the anti-TNF therapy, the serum fibulin-3 level decreased in patients. The fibulin-3 level correlated with CRP and ESR after anti-TNF treatment. Significant lowering of MRP8/14 was noted in the patients after anti-TNF therapy. No correlation between fibulin-3 and MRP8/14 was observed in the study group or in the control group., Conclusions: During the anti-TNF therapy, the serum fibulin-3 level decreased in RA patients. Serum MRP8/14 concentration also decreased. No correlation between fibulin-3 and MRP8/14 was observed in the study group before and after the treatment. We found a poor correlation between serum fibulin-3 and other cartilage metabolism biomarkers after anti-TNF therapy.

Background and Objective: Statins, 3-hydroxyl-3-methyl-glutharyl Coenzyme A reductase inhibitors showed their therapeutic potential in the treatment of atherosclerosis-related diseases. Recently, the properties of statins, separate from their lipid lowering activity have attracted much attention. These properties that cover a wide area of physiopathological activities including cell maturation, immune response regulation, tissue fibrosis, endothelial activity and are called pleiotropic activity. Many in vitro studies demonstrated significant, statins-dependent regulation of immune system reactivity, reduction of pro-inflammatory and pro-fibrotic cytokines as well as suppression of endothelial activity and damage., Methods: The present study reviewed the potential utility of statins as a concomitant regimen in the treatment of various connective tissue diseases. To address this we performed a methodical search though Pubmed database searching for term statins and pleiotropic effects and connective tissue disease or rheumatology., Results: One hundred and thirty one prominent research and review papers were identified and analyzed. Majority of research papers focused on laboratory models of statins activity, only a few of them analyzed data from human studies., Conclusion: Statins may have a therapeutic potential as a concomitant treatment for connective tissue diseases, that has been elegantly proven in many animal and laboratory studies. They deep interfere with immunological mechanism of autoantigen presentation, expressions of adhesion molecules. These phenomena may be recognized as the most important mode of action. Less is known about the potential of statins in clinical practice. Many small trials examined therapeutic potentials in various autoimmune diseases with contradictory results, disabling making the final conclusions. The future human studies should answer what patients population may benefit with concomitant statins' treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Objectives: Inflammation has been revealed to be associated with angiogenesis. Granulomatosis with polyangiitis (GPA) and immune complex small vessel vasculitis (ICSVV) are forms of systemic vasculitides of different pathogenesis. GPA is a necrotizing granulomatosis and ICSVV is associated with inflammation of postcapillary venules induced by deposits of immune complexes. The aim of the study was to determine serum levels of angiostatin and endostatin, natural angiogenesis inhibitors, in patients with GPA and ICSVV as well as healthy individuals., Material and Methods: Two groups of patients with GPA (20 patients) and ICSVV (20 patients) as well as 20 controls were investigated. All patients were investigated before initiation of immunosuppressive therapy or administration of corticosteroids. Angiostatin and endostatin levels were assayed with the ELISA method., Results: Enhanced serum levels of angiostatin and endostatin were found in patients with GPA but not in those suffering from ICSVV. In patients with GPA increased levels of angiogenesis inhibitors correlated with the disease activity. A correlation between angiostatin and endostatin levels was observed in all groups of investigated individuals., Conclusions: It is suggested that formation of necrotizing granulation is associated with profound activation of angiogenesis and an increase in serum levels of inhibitors is a phenomenon occurring during blood vessel formation in the granulation tissue. The obtained results confirm involvement of angiogenesis in pathogenesis of at least some forms of vasculitides and suggest the need for continuation of investigations in this field., Competing Interests: The authors declare no conflict of interest.

Objectives: Biologics are medications widely applied in the management of inflammatory rheumatic diseases. The drugs were found to be effective but their application is associated with some disadvantages. Medication with biologics is relatively expensive, and in Poland, it is carried out in specialized centers. The study was designed to evaluate various aspects of satisfaction and dissatisfaction of Polish patients treated with biologics., Material and Methods: An anonymous questionnaire was distributed in 23 Polish rheumatological centers involved in the treatment; 1212 returned questionnaires were used for analysis. Responses were received from 606 patients with rheumatoid arthritis, 427 with ankylosing spondylitis, 117 psoriatic arthritis, and 62 adult patients with juvenile idiopathic arthritis (in whom administration of the drugs had been introduced before they were 18 years old). The investigated group constituted about one-fifth of all rheumatic patients on biologics in Poland., Results: A beneficial or very beneficial influence of the medication on the state of physical health was found mostly in patients with rheumatoid arthritis (51.3 and 30.5%) and ankylosing spondylitis (51.0 and 36.8%). Family life was improved by the treatment especially in patients with ankylosing spondylitis (40.7 and 35.6% beneficial and very beneficial, respectively), sleep quality and sexual life mostly in those with ankylosing spondylitis (beneficial/very beneficial influence 41.5/38.4, and 38.7/23.9, respectively). There was a rather small influence of biological treatment on the financial situation of the patients. In general, satisfaction with the treatment was evaluated as positive or very positive in 88% of all investigated patients.In a significant part of the patients, transportation to the medical center was considered as a disadvantage of the treatment. About one-third of the patients considered laboratory and imaging tests to be done before initiation of the medication as a difficulty, and for about 40% waiting time for qualification for the medication was a significant disadvantage. The route of drug administration was without importance for 4/5 of the patients., Conclusions: Summing up, the results were similar in the patients suffering from various diseases although those with psoriatic arthritis felt the highest satisfaction (possibly due to the positive aesthetic effect), and those with ankylosing spondylitis had significant improvement in sexual life (probably due to younger age). Relatively low satisfaction was found in patients with juvenile idiopathic arthritis. There was a small influence of medication on financial status of the patients. Application of biologics has few disadvantages and most of them are associated with the organization of health services (waiting time for the tests, transportation to the medical centers)., Competing Interests: The authors declare no conflict of interest.

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.

Evidence from over 10 years of clinical experience demonstrates that biosimilar medicines approved in the European Union can be used for all their registered indications as safely as their originators and with no negative impact on therapeutic efficacy. The debate on the use of biosimilars in rheumatology focuses specifically on the safety of switching between biosimilars and reference products. Studies conducted to date, including randomised double-blind and open-label extension trials, have not demonstrated any significant differences in therapeutic efficacy or safety between patients switched from one medicine to another and those who were continued on a single medicine. According to the latest recommendations for the use of biosimilars in rheumatic diseases, developed by an international task force in 2017, there is no clinical evidence that a single switch from an originator to a biosimilar medicine is associated with any significant risk for patient safety or reduction in therapeutic efficacy., Competing Interests: The article was developed in cooperation with Sandoz. The authors were Sandoz consultants and lecturers (SK/219/10-2017).

Systemic sclerosis is a rare generalized disease with scleroderma, i.e. skin thickening as one of the most common symptoms. The disease has 2 main subsets, diffuse and limited forms. The subset known as systemic sclerosis sine scleroderma (ssSSc) is a very rare subset characterized by the total or partial absence of cutaneous manifestations of systemic sclerosis with the occurrence of internal organ involvement and serologic abnormalities. The classification of ssSSc into 3 groups was proposed. Type I (complete) is characterized by the lack of any cutaneous changes typical for the disease at least until systemic sclerosis-related insufficiency of any internal organ occurs. Type II (incomplete) is characterized by the absence of sclerodactyly, but other cutaneous involvements (e.g. calcifications, telangiectasies, pitting scars) can be found. Type III (delayed) is characterized by clinical internal organ involvement typical for systemic sclerosis that has appeared before skin changes (complete or incomplete). In general, the demographic and clinical characteristics of the ssSSc patients suggest that they are similar to those with diffuse or limited form of the disease. Diagnosis of ssSSc still remains difficult and this disease form should be considered in all cases of unexplained fibrotic involvement of the internal organs.