ASAS-EULAR recommendations for the management of axial spondyloarthritis: 2022 update.

OBJECTIVES: To update the Assessment of SpondyloArthritis international Society (ASAS)-EULAR recommendations for the management of axial spondyloarthritis (axSpA). METHODS: Following the EULAR Standardised Operating Procedures, two systematic literature reviews were conducted on non-pharmacological and pharmacological treatment of axSpA. In a task force meeting, the evidence was presented, discussed, and overarching principles and recommendations were updated, followed by voting. RESULTS: Five overarching principles and 15 recommendations with a focus on personalised medicine were agreed: eight remained unchanged from the previous recommendations; three with minor edits on nomenclature; two with relevant updates (#9, 12); two newly formulated (#10, 11). The first five recommendations focus on treatment target and monitoring, non-pharmacological management and non-steroidal anti-inflammatory drugs (NSAIDs) as first-choice pharmacological treatment. Recommendations 6-8 deal with analgesics and discourage long-term glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) for pure axial involvement. Recommendation 9 describes the indication of biological DMARDs (bDMARDs, that is, tumour necrosis factor inhibitors (TNFi), interleukin-17 inhibitors (IL-17i)) and targeted synthetic DMARDs (tsDMARDs, ie, Janus kinase inhibitors) for patients who have Ankylosing Spondylitis Disease Activity Score ≥2.1 and failed ≥2 NSAIDs and also have either elevated C reactive protein, MRI inflammation of sacroiliac joints or radiographic sacroiliitis. Current practice is to start a TNFi or IL-17i. Recommendation 10 addresses extramusculoskeletal manifestations with TNF monoclonal antibodies preferred for recurrent uveitis or inflammatory bowel disease, and IL-17i for significant psoriasis. Treatment failure should prompt re-evaluation of the diagnosis and consideration of the presence of comorbidities (#11). If active axSpA is confirmed, switching to another b/tsDMARD is recommended (#12). Tapering, rather than immediate discontinuation of a bDMARD, can be considered in patients in sustained remission (#13). The last recommendations (#14, 15) deal with surgery and spinal fractures. CONCLUSIONS: The 2022 ASAS-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA.

COVID-19: autoimmunity, multisystemic inflammation and autoimmune rheumatic patients.

Coronavirus disease 2019 (COVID-19) is associated with autoimmunity and systemic inflammation. Patients with autoimmune rheumatic and musculoskeletal disease (RMD) may be at high risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this review, based on evidence from the literature, as well as international scientific recommendations, we review the relationships between COVID-19, autoimmunity and patients with autoimmune RMDs, as well as the basics of a multisystemic inflammatory syndrome associated with COVID-19. We discuss the repurposing of pharmaceutics used to treat RMDs, the principles for the treatment of patients with autoimmune RMDs during the pandemic and the main aspects of vaccination against SARS-CoV-2 in autoimmune RMD patients.

Development of an environmental contextual factor item set relevant to global functioning and health in patients with axial spondyloarthritis.

OBJECTIVE: To describe the development of an Environmental contextual factors (EF) Item Set (EFIS) accompanying the disease specific Assessment of SpondyloArthritis international Society Health Index (ASAS HI). METHOD: First, a candidate item pool was developed by linking items from existing questionnaires to 13 EF previously selected for the International Classification of Functioning, Disability and Health (ICF) /ASAS Core Set. Second, using data from two international surveys, which contained the EF item pool as well as the items from the ASAS HI, the number of EF items was reduced based on the correlation between the item and the ASAS HI sum score combined with expert opinion. Third, the final English EFIS was translated into 15 languages and cross-culturally validated. RESULTS: The initial item pool contained 53 EF addressing four ICF EF chapters: products and technology (e1), support and relationship (e3), attitudes (e4) and health services (e5). Based on 1754 responses of axial spondyloarthritis patients in an international survey, 44 of 53 initial items were removed based on low correlations to the ASAS HI or redundancy combined with expert opinion. Nine items of the initial item pool (range correlation 0.21-0.49) form the final EFIS. The EFIS was translated into 15 languages and field tested in 24 countries. CONCLUSIONS: An EFIS is available complementing the ASAS HI and helps to interpret the ASAS HI results by gaining an understanding of the interaction between a health condition and contextual factors. The EFIS emphasizes the importance of support and relationships, as well as attitudes of the patient and health services in relation to self-reported health.

Long-term clinical results from 10 years follow-up after radiosynoviorthesis: a prospective observational study.

BACKGROUND: The aim of this study was to assess the long-term anti-inflammatory effect and safety of 90-Yttrium and 166-Holmium radiosynoviorthesis (RSO) for treating chronic knee synovitis of various origins. METHODS: A total of 820 patients were included in this study and were followed up to 10 years after the procedure for objective and subjective changes in signs and symptoms of inflammation. RESULTS: Five years after RSO, excellent and good results were seen in 71% (95% CI 67-74%) of patients. Six, seven, eight and nine years following RSO, efficacy did not decrease significantly. Ten years after RSO, the effectiveness of the therapy fell to 65% (95% CI 59-71%). Overall, 64% of patients did not need another joint puncture ten years after RSO. We achieved excellent to good results at 5 years in 79% of patients with rheumatoid arthritis, 59% with ankylosing spondylitis, and 62% with osteoarthritis. Efficacy was mainly affected by the local X-ray stage of the knee joint. A significant association was also found between the diagnosis of the underlying disease and the success of radiosynoviorthesis. Efficacy, however, was not substantially affected by any of the following factors: the duration of synovitis, the number of punctures before radiosynoviorthesis, the number of intraarticular steroid injections before the procedure, or the number of interventions before radiosynoviorthesis (radiotherapy, surgery). CONCLUSIONS: Radiosynoviorthesis is an effective long-term method of treating chronic synovitis. The treatment showed the most favorable effects in patients with rheumatoid arthritis and those with mild to moderate degenerative osseous changes.

Assessing the risk of rapid radiographic progression in Hungarian rheumatoid arthritis patients.

BACKGROUND: The outcome of rheumatoid arthritis (RA) should be determined early. Rapid radiological progression (RRP) is > or = 5 units increase according to the van der Heijde-Sharp score within a year. The risk of RRP can be estimated by a matrix model using non-radiographic indicators, such as C-reactive protein (CRP), rheumatoid factor (RF) and swollen joint count (SJC). PATIENTS AND METHODS: A non-interventional, cross-sectional, retrospective study was conducted in eleven Hungarian arthritis centres. We assessed RRP risk in biologic-naïve RA patients with the prevalence of high RRP risk as primary endpoint. RRP was calculated according to this matrix model. As a secondary endpoint, we compared RRP in methotrexate (MTX) responders vs non-responders. RESULTS: We analyzed data from 1356 patients. Mean CRP was 17.7 mg/l, RF was 139.3 IU/ml, mean 28-joint disease activity score (DAS28) was 5.00 and mean SJC was 6.56. Altogether 18.2% of patients had high risk (≥40%) of RRP. RA patients with high RRP risk of RRP (n = 247) had significantly lower age compared to those with RRP < 40% (n = 1109). MTX non-response (OR: 16.84), male gender (OR: 1.67), erosions at baseline (OR: 1.50) and ACPA seropositivity (OR: 2.18) were independent predictors of high-risk RRP. Male gender (OR: 5.20), ACPA seropositivity (OR: 4.67) and erosions (OR: 7.98) were independent predictors of high RRP risk in MTX responders. CONCLUSIONS: In this Hungarian study, high RRP risk occurred in 18% of RA patients. These patients differ from others in various parameters. RRP was associated with non-response to MTX.

A prospective observational study on the long-term results of 90Yttrium citrate radiosynoviorthesis of synovitis in osteoarthritis of the knee joint.

OBJECTIVES: Radiosynoviorthesis (RSO) is used for the treatment of inflammatory joint diseases. However, there are no long-term results published comparing it to conservative therapy. Therefore, the aim of this prospective observational study was to evaluate response rates after radionuclide therapy in patients suffering from knee osteoarthritis over a time period of 10 years. METHODS: Radionuclide therapy with intra-articular administration of colloidal 90Yttrium citrate was performed in osteoarthritic patients [Kellgren-Lawrence grades I/II (n = 69) and Kellgren-Lawrence grade III (n = 72)]. RESULTS: In patients with early-stage disease, an excellent/good response with respect to pain, joint mobility, and function was observed in 82.5% for 1 year and in 73.7% for 8 years after therapy. Responses declined to 50% at 10 years post treatment. In grade III patients, an excellent/good response was observed in 45.9%; a decline to 41.2% was observed in the first 8 years. In this group, the number of patients available for follow-up after 9 and 10 years dropped significantly from 51 patients after 8 years to only 30 patients after 9 years, and to nine patients after 10 years. As a result, these response rates were not appraisable. CONCLUSION: Long-term results of radiosynoviorthesis in knee osteoarthritis are excellent/good in many patients. The response rate depends on Kellgren-Lawrence stages, and early-stage radionuclide therapy for osteoarthritis is suggested.

2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis.

To update and integrate the recommendations for ankylosing spondylitis and the recommendations for the use of tumour necrosis factor inhibitors (TNFi) in axial spondyloarthritis (axSpA) into one set applicable to the full spectrum of patients with axSpA. Following the latest version of the European League Against Rheumatism (EULAR) Standardised Operating Procedures, two systematic literature reviews first collected the evidence regarding all treatment options (pharmacological and non-pharmacological) that were published since 2009. After a discussion of the results in the steering group and presentation to the task force, overarching principles and recommendations were formulated, and consensus was obtained by informal voting. A total of 5 overarching principles and 13 recommendations were agreed on. The first three recommendations deal with personalised medicine including treatment target and monitoring. Recommendation 4 covers non-pharmacological management. Recommendation 5 describes the central role of non-steroidal anti-inflammatory drugs (NSAIDs) as first-choice drug treatment. Recommendations 6-8 define the rather modest role of analgesics, and disprove glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) for axSpA patents with predominant axial involvement. Recommendation 9 refers to biological DMARDs (bDMARDs) including TNFi and IL-17 inhibitors (IL-17i) for patients with high disease activity despite the use (or intolerance/contraindication) of at least two NSAIDs. In addition, they should either have an elevated C reactive protein and/or definite inflammation on MRI and/or radiographic evidence of sacroiliitis. Current practice is to start with a TNFi. Switching to another TNFi or an IL-17i is recommended in case TNFi fails (recommendation 10). Tapering, but not stopping a bDMARD, can be considered in patients in sustained remission (recommendation 11). The final two recommendations (12, 13) deal with surgery and spinal fractures. The 2016 Assessment of SpondyloArthritis international Society-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA.

Intercentre variance in patient reported outcomes is lower than objective rheumatoid arthritis activity measures: a cross-sectional study.

Objective: To assess intercentre variability in the ACR core set measures, DAS28 based on three variables (DAS28v3) and Routine Assessment of Patient Index Data 3 in a multinational study. Methods: Seven thousand and twenty-three patients were recruited (84 centres; 30 countries) using a standard protocol in the Quantitative Standard Monitoring of Patients with RA study. Analysis of variance (ANOVA) and mixed-effect analysis of covariance models were used to model the relationship between study centre and different patient-reported and physician-reported RA activity measures. These models were built to adjust for the remaining ACR core set measure (for each ACR core set measure or each composite index), socio-demographics and medical characteristics. ANOVA and analysis of covariance models yielded similar results, and ANOVA tables were used to present variance attributable to recruiting centre. Results: The proportion of variances attributable to recruiting centre was lower for patient reported outcomes (PROs: pain, HAQ, patient global) compared with objective measures (joint counts, ESR, physician global) in all models. In the full model, variance in PROs attributable to recruiting centre ranged from 1.53% for patient global to 3.71% for HAQ compared with objective measures that ranged from 5.92% for physician global to 9.25% for ESR; and was lower for Routine Assessment of Patient Index Data 3 (2.6%) compared with DAS28v3 (11.75%). Conclusion: Intercentre variability in PROs is lower than objective measures of RA activity demonstrating that PROs may be more comparable across centres, and the need for standardization of objective measures.

Adaptation of the osteoarthritis-specific quality of life scale (the OAQoL) for use in Germany, Hungary, Italy, Spain and Turkey.

The Osteoarthritis Quality of Life scale (OAQoL) is specific to individuals with osteoarthritis. The present study describes the adaptation of the OAQoL for use in the following five European languages: German, Hungarian, Italian, Spanish and Turkish. The study involved three stages in each language; translation, cognitive debriefing (face and content validity) and validation. The validation stage assessed internal consistency (Cronbach's alpha), reproducibility (test-retest reliability using Spearman's rank correlations), convergent and divergent validity (correlations with the Health Assessment Questionnaire, The Western Ontario and McMaster Universities Index of osteoarthritis and Nottingham Health Profile) and known group validity. The OAQoL was successfully translated into the target languages with minimal problems. Cognitive debriefing interviewees found the measures easy to complete and identified few problems with content. Internal consistency ranged from 0.94 to 0.97 and test-retest reliability (reproducibility) from 0.87 to 0.98. These values indicate that the new language versions produce very low levels of measurement error. Median OAQoL scores were higher for patients reporting a current flare of osteoarthritis in all countries. Scores were also related, as expected, to perceived severity of osteoarthritis. The OAQoL was successfully adapted for use in Germany, Hungary, Italy, Spain and Turkey. The addition of these new language versions will prove valuable to multinational clinical trials and to clinical practice in the respective countries.

[Peroral and transdermal application of non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of regional musculoskeletal pain syndromes]. / Nem szteroid gyulladáscsökkentok peroralis és transdermalis alkalmazása regionális mozgásszervi fájdalmi szindrómákban.

In this review the available evidences regarding the most frequently applied medication (peroral and transdermal non-steroidal anti-inflammatory agents) for the most frequent musculoskeletal complaints (regional pain syndromes) have been collected for the appropriate medical professionals who are most frequently faced with these conditions (general practitioners, rheumatologists, orthopedics, occupational and sports medicine experts). The special population at risk (with repeated and high energy overuse because of occupational or sport activities) and the pathology of their syndromes are identified. Mode of action, pharmacological properties of the non-steroidal anti-inflammatory drugs and the unwanted effects of their application especially in infants and elderly are highlighted. Recommendations of the general and specific pain management guidelines have been selected and listed in the review. Orv Hetil. 2017; 158(Suppl. 3): 3-30.

[Initial experiences with VATS lobectomy]. / VATS-lobectomiák kezdeti tapasztalatai.

OBJECTIVE: The authors analyse the experience of videothoracoscopic (VATS) lung lobectomies performed since December 2010 at the Thoracic Surgery Department of Markusovszky University Teaching Hospital. PATIENTS AND METHOD: 78 patients (44 men and 34 women) underwent VATS lobectomy. The average age was 61.2 years ranging from 30 to 80. The indications were peripheral malignancy (35 cases) or the suspicion of that (43 cases), presence of curable distant metastasis was not considered as contraindication. RESULTS: In the initial period the operation time was quite long, but shortly after the duration of surgery became almost similar to lobectomies via thoracotomy. Late reoperation was performed in two cases, one for chronic pneumothorax and one for port-site metastasis. 10 vessel and two bronchial injuries occurred, eight of them needed conversion into axillary thoracotomy (conversion rate 10.26%). The postoperative pain was significantly less than after thoracotomy. CONCLUSION: VATS lobectomy is a safe procedure with less surgical stress and without oncological compromise.

Comparison of two referral strategies for diagnosis of axial spondyloarthritis: the Recognising and Diagnosing Ankylosing Spondylitis Reliably (RADAR) study.

OBJECTIVE: To determine which of two referral strategies, when used by referring physicians for patients with chronic back pain (CBP), is superior for diagnosing axial spondyloarthritis (SpA) by rheumatologists across several countries. METHODS: Primary care referral sites in 16 countries were randomised (1 : 1) to refer patients with CBP lasting >3 months and onset before age 45 years to a rheumatologist using either strategy 1 (any of inflammatory back pain (IBP), HLA-B27 or sacroiliitis on imaging) or strategy 2 (two of the following: IBP, HLA-B27, sacroiliitis, family history of axial SpA, good response to non-steroidal anti-inflammatory drugs, extra-articular manifestations). The rheumatologist established the diagnosis. The primary analysis compared the proportion of patients diagnosed with definite axial SpA by referral strategy. RESULTS: Patients (N=1072) were referred by 278 sites to 64 rheumatologists: 504 patients by strategy 1 and 568 patients by strategy 2. Axial SpA was diagnosed in 35.6% and 39.8% of patients referred by these respective strategies (between-group difference 4.40%; 95% CI -7.09% to 15.89%; p=0.447). IBP was the most frequently used referral criterion (94.7% of cases), showing high concordance (85.4%) with rheumatologists' assessments, and having sensitivity and a negative predictive value of >85% but a positive predictive value and specificity of <50%. Combining IBP with other criteria (eg, sacroiliitis, HLA-B27) increased the likelihood for diagnosing axial SpA. CONCLUSIONS: A referral strategy based on three criteria leads to a diagnosis of axial SpA in approximately 35% of patients with CBP and is applicable across countries and geographical locales with presumably different levels of expertise in axial SpA.

[Physiotherapy from the view of health insurance financing]. / A fizioterápia az egészségbiztosítás szemszögébol.

Physiotherapy lacks studies performed with the use of the modern research methodology and, therefore, its use based on empirical considerations. International practice guidelines do not recommend unequivocally the use of all kinds of physiotherapy with the exception of exercise therapy, but Hungarian guidelines support its use in the treatment of several different conditions. National health insurance in Hungary provides financial support for the use of physiotherapy in the fields of home care, out- and inpatient care and spa treatment. In 2011 national health insurance in Hungary supported spa treatments with 4 billion HUF, and the most frequently used treatment was thermal bath in about 2 million occasions. National health insurance in Hungary spent about 1 billion HUF for physiotherapy used in outpatient care; both ultrasound and interference treatments were financed in 2 million occasions in 2011.

[Long-term survival after lung-sparing central bronchoplastic procedures [CBPs] for malignant tumors]. / Hosszú túléléssel járó malignus tumor miatti tüdomegtartó centrális fohörgoplasztikáink.

BACKGROUND: Bronchial malignancies are leading tumour-related cause of death. Prolonged survival can only be expected after radical resections. Central bronchoplastic procedures, which save the whole lung parenchyma, however, may play a role. AIM: These bronchoplastic procedures can be good alternatives for pulmonectomies. The value of these operations can be evaluated by postoperative mortality complication, and the survival rate. MATERIAL AND METHODS: In the period of 1985-2012 we operated 7130 bronchial carcinomas. Of these, 7 cases of 80 central broncoplastics we preserved the whole lung (in one case as an alternative for inoperability, in 6 patients as an option instead of pulmonectomy). The indications were carcinoid in four cases, epidermoid carcinoma, mucoepidermoid carcinoma and main carina SCLC after induction chemo-radiotherapy. The average age of the 4 male and of the 3 female patients were 28.5 (14-58) years. In 5 cases the right main bronchus, while in one case the left main bronchus was resected and the bronchial tree was reconstructed. In one case (SCLC patient) we made a complete carina resection and end-to-end anastomosis between the trachea and the rebuilt neocarina to preserve both lungs. The anastomosis was made with 3-4/0 PDS interrupted sutures above a sterile tube (6 cases) and in one case due to a jet catheter which were positioned through the operation field into the distal part of the main healthy bronchus. RESULTS: There was no operative mortality nor bronchopleural fistula. In the early postoperative period we applied repeated bronchoscopic suctions. In the patient with carina SCLC anastomosis stenosis developed. The main bronchi were temporarily stented. This patient is fit 174 months after the intervention, the Karnofsky index mesures to 90%. Other 5 patients are alive without any consequences of recurrence nor metastasis. The patient with epidermoid carcinoma died 83 months later because of distant metastases of a SCLC, originating from the contralateral lung. The mean survival is 118 (7-233) months. CONCLUSION: In case of some properly selected localised mainstem bronchial malignancies, such as young age and low grade malignancy, radical surgical interventions can be performed with long term survival preserving the whole lung due to special CBPs. Some such successful series and case reports (under 200 cases) can be found in the literature but the long-term survival data was not demonstrated in most publications. In Hungary there has not been any publications yet on such a successful series with long term survival. These results are remarkable within international standards.

[COVID-19 infections and effectiveness of the vaccination among healthcare workers]. / A COVID­19-fertozés és a védooltások hatásosságának vizsgálata egészségügyi dolgozókon.

INTRODUCTION: New variants of the SARS-CoV-2 coronavirus are constantly appearing, causing the COVID-19 pandemic. From November 2021, most infections were caused by the Omicron coronavirus variant. OBJECTIVE: The aim of this prospective observational cohort study was to estimate the incidence of COVID-19 infections in the high-risk healthcare workers after two BNT162b2 mRNA Pfizer-BioNTech vaccines and the subsequent booster vaccine, as well as the effectiveness, the safety and the humoral immune response of the vaccines. METHOD: We started the two Pfizer-BioNTech ((BNT162b29) vaccinations of healthcare workers of the Polyclinic of the Hospitaller Brothers of St. John between January 07 and March 08, 2021. The choice of the type and timing of the third booster vaccination was voluntary. The workers were followed up between January 07, 2021 and June 29, 2022. The infection rate, adverse events of the vaccination, risk factors to infection and the kinetics of anti-spike (S) antibody and anti-nucleocapsid (N) antibody serum level were evaluated. RESULTS: The data of 294 healthcare workers - 96 medical doctors, 127 nurses and 71 workers in hospital - who had at least three antibody level measurements were analyzed. The third booster vaccine was given to 280 workers, the distribution of the vaccines was the following: Pfizer-BioNTech (BNT162b29) vaccine (n = 210), Moderna COVID-19 (mRNA-1273) vaccine (n = 37), Sinopharm COVID-19 vaccine (n = 21), Janssen COVID-19 (n = 10), AstraZeneca (ChAdOx1 nCoV-19) vaccine (n = 2). Infection occurred in 121 cases (41%) during the observation period. The course of the COVID-19 infections was mostly mild (97%) and recovered within a week. During the observational period, 2 workers died: a 56-year-old woman died after two vaccinations for reason unrelated to COVID-19 infection, and a 58-year-old man died after the booster vaccination, following COVID-19 infection. The incidence of infection did not correlate with age, sex, comorbidities, smoking, occupation and BMI. The median titre of anti-S antibody serum level increased one month after the second vaccination of the basic immunization (1173.0 U/ml) and decreased slowly until the 8th month (678.5-625.8-538.0 U/ml) after the basic vaccination. One month after the booster vaccination, the median titre of anti-S antibody serum level increased significantly (16 535 U/ml), and showed a decreasing trend in the 3rd month after the booster vaccination (9697.7 U/ml). An exceptionally high S antibody serum level increasing after the basic (>10 000 U/mL) and booster (>60 000 U/m) vaccination showed a correlation with prior COVID-19 infection. The median cut-off index (COI) of anti-N antibody was not affected by vaccination, the increasing of the titre is related to the infection. CONCLUSION: The booster vaccination had less effect on the infection caused by Omicron variant, but the course of the infection was milder. Compared to the basic immunisation, the booster vaccination caused a significant increase in the S antibody level. An exceptionally high S antibody level correlated with prior COVID-19 infection. Orv Hetil. 2023; 164(5): 163-171.

Patient's global assessment of disease activity and patient's assessment of general health for rheumatoid arthritis activity assessment: are they equivalent?

OBJECTIVES: To assess (A) determinants of patient's global assessment of disease activity (PTGL) and patient's assessment of general health (GH) scores of rheumatoid arthritis (RA) patients; (B) whether they are equivalent as individual variables; and (C) whether they may be used interchangeably in calculating common RA activity assessment composite indices. METHODS: Data of 7023 patients from 30 countries in the Quantitative Standard Monitoring of Patients with RA (QUEST-RA) was analysed. PTGL and GH determinants were assessed by mixed-effects analyses of covariance models. PTGL and GH equivalence was determined by Bland-Altman 95% limits of agreement (BALOA) and Lin's coefficient of concordance (LCC). Concordance between PTGL and GH based Disease Activity Score 28 (DAS28), Clinical Disease Activity Index (CDAI) and Routine Assessment of Patient Index Data 3 (RAPID3) indices were calculated using LCC, and the level of agreement in classifying RA activity in four states (remission, low, moderate, high) using κ statistics. RESULTS: Significant differences in relative and absolute contribution of RA and non-RA related variables in PTGL and GH ratings were noted. LCC of 0.64 and BALOA of -4.41 to 4.54 showed that PTGL and GH are not equivalent. There was excellent concordance (LCC 0.95-0.99) for PTGL and GH based DAS28, CDAI and RAPID3 indices, and >80% absolute agreement (κ statistics 0.75-0.84) in RA activity state classification for all three indices. CONCLUSIONS: PTGL and GH ratings differ in their determinants. Although they are individually not equivalent, they may be used interchangeably for calculating composite indices for RA activity assessment.

Continuous efficacy of etanercept in severe and advanced ankylosing spondylitis: results from a 12-week open-label extension of the SPINE study.

OBJECTIVE: To evaluate the longer-term efficacy of etanercept in patients with severe and advanced active AS. METHODS: Seventy-seven patients who completed the randomized, double-blind, placebo-controlled 12-week SPINE study enrolled in a 12-week open-label extension and received s.c. etanercept 50 mg once weekly. The etanercept/etanercept group received a total of 24 weeks treatment with etanercept (n = 38); the placebo/etanercept group received placebo during the double-blind study then 12 weeks' etanercept treatment during the open-label extension (n = 39). RESULTS: At the end of the open-label extension, BASDAI scores in the etanercept/etanercept group had further decreased beyond reductions observed during the double-blind study [mean (s.d.) change from baseline -37.6 (22.4) at end of extension vs -27.4 (23.8) at end of double-blind study]. Mean (s.d.) BASDAI scores also improved in the placebo/etanercept group once switched to etanercept [-28.6 (24.3) vs -15.0 (20.0)]. Similar trends were observed in BASFI and BASMI scores. In the placebo/etanercept group, total back pain decreased to similar levels achieved in the etanercept group in the double-blind study. Pain levels continued to decrease with longer-term etanercept therapy in the etanercept/etanercept group. CONCLUSION: Despite the improvements in symptoms and inflammatory markers observed shortly after initiation of once-weekly etanercept, there was no notable plateauing effect on patient-reported outcomes. Indeed, signs and symptoms of severe and advanced active AS continued to improve after up to 24 weeks, treatment with etanercept.

Specific expression of PAD4 and citrullinated proteins in lung cancer is not associated with anti-CCP antibody production.

Anti-citrullinated protein antibodies (ACPAs), produced against citrullinated proteins, are diagnostic and prognostic markers of rheumatoid arthritis (RA). The underlying mechanism that explains the connection of smoking, citrullination [catalyzed by peptidyl arginine deiminases (PADs)] and ACPAs is still unclarified in RA. Thus, we searched for a non-arthritic model in which an increased cell death allows the formation of autoantibodies. Data supporting that lung cancer might be a good candidate are as follows: (i) smoking plays a role in its pathogenesis, (ii) the disease is frequently accompanied by paraneoplastic syndrome, (iii) smoking increases citrullination in the lung, (iv) various types of malignancies are associated with increased citrullination and (v) lung cancer tissue shows similarities with RA synovium. Serum PAD4, rheumatoid factor (RF) and ACPA levels were measured in 42 lung cancer patients; expression of cytokeratin 7 (CK7), PAD4 and citrullinated proteins was visualized in 113 lung cancer tissues. All parameters were analyzed in correlation with smoking history. None of the patients had polyarthritis or autoimmune disease. Significantly increased RF levels were associated with higher PAD4 levels in smoker lung cancer patients compared with non-smokers. Both PAD4 and citrullination immunostaining strongly correlated with that of CK7 in lung cancer, however, did not differ according to smoking history. Two of 30 smoker lung cancer patients had high anti-cyclic citrullinated peptide levels. In conclusion, PAD4 and citrullination may be helpful in distinguishing lung cancer from healthy tissue. Smoking, abnormal serum PAD4 and RF levels may not be sufficient for the production of ACPAs and development of autoimmunity.

Real-world evidence on methotrexate-free subcutaneous tocilizumab therapy in patients with rheumatoid arthritis: 24-week data from the SIMPACT study.

Objectives: The aim of the SIMPACT study was to evaluate the efficacy and safety of MTX-free s.c. tocilizumab (TCZ) therapy in RA patients. Methods: SIMPACT was an open-label, non-controlled, non-randomized, non-interventional study, in which RA patients for whom the treating physicians ordered s.c. TCZ were observed during a 24-week treatment period in Hungarian centres. Although the use of MTX was avoided during the study period, other conventional synthetic DMARDs, oral CSs and NSAIDs were allowed. Study endpoints included the change in DAS28 and clinical activity index (CDAI) scores, the proportion of patients achieving remission in the whole population and in subgroups defined based on prior RA treatment history, and age, weight or biological sex post hoc. The extent of supplementary medication use was monitored. Results: Three hundred and thirty-seven RA patients were enrolled in 18 study centres. TCZ therapy significantly decreased the disease activity measured by both DAS28 (P = 0.0001) and CDAI (P = 0.0001). Clinical response was more pronounced in biologic-naïve patients and was lower in patients >75 years of age. In the whole population, DAS28 ESR or CRP and CDAI remission rates were 70.10%, 78.95% and 33.59%, respectively. In patients <45 years of age, the CDAI remission rate doubled (67.86%). A significant decrease in the frequency of co-administered medication was reported, including oral CSs and DMARDs. Conclusion: Real-world clinical evidence on s.c. TCZ reported here is in line with the efficacy outcomes of randomized clinical trials. Subgroup analysis revealed that TCZ was more effective in biologic-naïve patients and in those <75 years old. Trial registration: ClinicalTrials.gov, http://www.clinicaltrials.gov, NCT02402686.