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Background. The evolution of the therapeutic arsenal in inflammatory rheumatic diseases has dramatically improved their evolution and prognosis. On the other hand, the information of the safety data, especially for conditions that may appear in a longer time of exposure, are not reflected by clinical trials, due to their limited time design. Patient registries are a valuable source of safety data applicable to real-world (unselected) patients. The evaluation of these data completes the evidence from the various development programs, with the aim of more concrete knowledge of each therapeutic class (therapeutic agent). Aim. The present report descriptively presents the adverse events (AE) of special interest, recorded by the Romanian Registry of Rheumatic Diseases (RRBR), during 2022, in relation to the dynamics of the recent years. Methods. The observational study included all AEs reported in the RRBR in 2022, their severity class, the relationship with exposure to the therapeutic agent. Results. For a cohort of 10676 patients who were exposed to at least one course of treatment, with data in the RRBR during 2022, there were 669 AEs reported: 432 reports for patients with rheumatoid arthritis (RA), 195 records for patients with ankylosing spondylitis (AS) and 42 reports for patients with psoriatic arthritis (PsA). The most common AEs were infections, especially in RA patients. Of all AEs, 94 (14%) were serious AEs, the majority reported in the RA group (16%). A number of 15 MACE, 13 solid malignancy and 19 deaths were reported in the last year. Conclusion. The distribution of EA by disease, the dominance in RA, as well as the distribution by therapeutic groups is in accordance with scientific data, with the exception of breast cancer, which is more frequently reported in RRBR. EA are underreported in the destinated section in the RRBR, an aspect that gives a limit of this report. This represents an unmet need in terms of safety data reporting, that calls for increased knowledge of EA reporting requirements.

Objective. The objective of this cross-sectional study was to analyze data available in the Romanian Registry of Rheumatic Diseases (RRBR) in 2022 for axial spondyloarthritis (axSpA) patients treated with biologic disease modifying anti-rheumatic drugs (bDMARDs). Methods. From the RRBR electronic database were collected multiple variables, including patient’s demographic and clinical characteristics, treatment characteristics, patterns of treatment use (initiations, continuations, switching, tapering), and treatment efficacy data of axSpA patients, from 1 January 2022 to 31 December 2022. Results. In 2022, a total of 4315 axSpA patients were registered in the RRBR database: 70% were men, 48.4 years mean age, 13.3 years mean disease duration, 90% with radiographic axSpA, with high prevalence of extra-musculoskeletal manifestations and cardiovascular comorbidities. Most patients (88%) were treated with a tumor necrosis factor inhibitor (TNFi), usually in monotherapy. The most frequently prescribed bDMARDs were adalimumab (36%), etanercept (32%) and secukinumab (12%). The uptake of biosimilars reached one third of patients from molecules with available biosimilars in 2022. Most patients had a good clinical response, irrespective of clinical form, disease duration, type of medication or line of treatment. Medication switching was needed in 10% of patients, the main reason for switching was secondary loss of efficacy. Medication tapering was implemented in 11% of patients, and it was successful in 90% of cases. Conclusion. Data from RRBR provide a valuable real-world view of clinical practice at the national level regarding biologic treatment of axSpA patients.

Objective. The study aimed at determining whether RA patients starting or stopping biosimilars differ in any regard from those starting or stopping originals. Methods. Data on RA patients was obtained from the Romanian Registry of Rheumatic Diseases (RRBR) database between January 1st, 2022, and December 31st, 2022, encompassing all Romanian RA patients fulfilling the national criteria for bo/bsDMARD initiation, continuation or switching. Results. Etanercept and adalimumab predominated for initiations of biosimilars. Most entries on biosimilars originated from originals (including non-medical switches) and from bDMARDs without biosimilars. A historical effect of accumulation of patients was observed, manifested in the fact that originals still dominated the group of patients continuing their treatment, with the exception of infliximab, while biosimilars tended to be continued in younger patients and in patients with shorter disease duration. Cases categorized more severe by both patients, their doctors and their disease activity were preferably reserved for originals. In patients continuing their previous bDMARD, biosimilars exhibited higher DAS28 and SDAI remission rates. Conclusion. RRBR data from 2022 confirm the market rise of biosimilars in RA, but also physicians’ prudence in prescribing them to highly active cases. In the Romanian RA cohort, biosimilars are overall more effective in holding remission than originals.

Objective. The study aimed at characterizing the evolution of RA treatment with b/tsDMARDs in Romania, since the end of the SARS-CoV-2 pandemic and the national approval of JAKi. Methods. Data on RA patients was obtained from the Romanian Registry of Rheumatic Diseases database between January 1st, 2022, and December 31st, 2022, encompassing all Romanian RA patients fulfilling the national criteria for b/ tsDMARD initiation. Results. The RRBR database contained 5396 active RA patients: 83.2% female, 59.9 years mean age, 13 years median disease duration, 86.7% RF positive, 81.7% ACPA positive, with a high prevalence of cardiovascular comorbidities, 89.8% receiving at least one csDMARD, most often methotrexate (48.7%), with 6.3% on glucocorticoids, 78.8% on bDMARDs (especially etanercept - 27.6%, adalimumab - 18.1% and tocilizumab - 14.0%) and 21.2% on JAKi (most often on baricitinib - 11.4%), with a 58.2% DAS28-defined remission rate and a 34.3% SDAI-defined remission rate. Conclusion. The Romanian cohort of RA patients on b/tsDMARDs observed the both classical phenotypic characteristics of RA and local cohort characteristics. JAKi prescription has gained a significant increase. Capturing data on real-world patients filtered by stringent criteria for high disease activity and poor prognosis factors, the RRBR database proves to be an extremely useful insight into the evolution of RA pharmacologic treatment.

Lung disease is the second most frequent extra articular manifestation in rheumatoid arthritis (RA) patients. It can be present in up to 80% RA cases and represents a major cause of morbidity and mortality. One of the most common types of lung involvement in RA patients is the interstitial lung disease (ILD). Computed tomography studies show evidence of ILD in a large proportion of patients with RA (over 50% in some studies) and it can be clinically symptomatic in 5% of cases. The CT aspect classifies four forms of ILD, listed in order of frequency: usual interstitial pneumonia (UIP) - the most common form, non-specific interstitial pneumonia (NSIP), organizing pneumonia (OP) and diffuse alveolar damage (DAD) which is the least common form. We present a long-standing case of rheumatoid arthritis overlapping systemic sclerosis with interstitial lung disease.

Haemophagocytic lymphohistiocytosis (HLH) is an underrecognized hyperinflammatory condition with a high mortality, characterized by inappropriate survival of histiocytes and cytotoxic T cells (CTLs), leading to a cytokine storm, haemophagocytosis and multi-organ damage (1). The currently accepted terminology includes two forms of HLH: the primary or familial HLH (fHLH) and the secondary HLH (sHLH) (2). The sHLH associated with rheumatic conditions is known as macrophage activation syndrome (MAS). MAS can develop at any time during the evolution of the rheumatic diseases: at the beginning, during flare of the disease or during intercurrent infections – mostly with viral trigger. We present a case of MAS in an patient with adult-onset Still Disease. It is of great importance to be recognized in early stages, because if promptly treated it might respond well to combination therapy of glucocorticoids and IL1- blockers.

Enthesitis is a distinctive feature of psoriatic arthritis. New imaging techniques help to better understand the pathophysiology of entheses, being one of the essential factors of the subclinical and prodromal stages of psoriatic arthritis. This paper aims to review the main clinical scores, imaging scores, confounding factors that might influence the interpretation of results and the impact of medication on enthesitis in psoriatic arthritis.

Background. There is a time sensitive window of opportunity in rheumatoid arthritis (RA) in which therapeutic intervention is more effective, the disease being more susceptible to the immunomodulatory effects of the remissive medication. The goal is to prevent osteo-articular damage, which causes severe functional deficit, and to raise the chance to lead the disease in remission. Evolution towards RA represents a multi-step process. In other medical fields prevention has the same important role as treatment, so could we in the future switch again the therapeutic paradigm in RA, from early treatment to prevention of RA, by treating patients with high risk of developing disease? Initiating treatment in the pre-RA phases could potentially lead to a better immune modulation or even preventing disease development by acting on less mature pathogenic processes. Treating in the initial symptomatic phase of the disease could potentially be more effective in reducing disease persistence and the development of structural lesions. The clinically suspect arthralgia (CSA) definition offers a support of clinical parameters for future longitudinal studies, where together with para clinical parameters, laboratory studies and imagistic studies, could lead to the development of imminent RA classification criteria. Currently there are more ongoing studies that have the primary objective to prove this concept with different subpopulations and treatments, but most of them have inclusion criteria based on the presence of autoantibodies. The publication of this trials results in the next decade will help to better understand the efficacy of therapeutic intervention with the scope of preventing chronic arthritis and what subset of patients at risk to treat. There are no recommendations for management of CSA, but current practice is symptomatic treatment with nonsteroidal anti-inflammatory drugs, pain relievers and of course monitoring.

Imaging evaluation in rheumatoid arthritis (RA) has evolved significantly in last decades. Even if the modern imaging technics like ultrasound and magnetic resonance imaging have unequivocal place in the assessment of early disease (especially for synovial inflammation, bone oedema, erosions), radiographic evaluation of hands and feet is still the most widely used imaging technic for quantification of joint damage in RA. In the current review we aim to address some practical issues related to the radiographic evaluation in RA from daily practice perspective, followed by a broader approach from the clinical trials point of view.

Background. Registries data are important contributors to complement information provided by randomized controlled trial reports in terms of effectiveness and safety evaluation for anti-rheumatic drugs used in clinical practice. Objectives. We aimed to estimate the 12 month secukinumab retention rate and effectiveness in patients with axial spondyloarthritis. Data from the Romanian Registry of Rheumatic Diseaases (RRBR, in Romanian) were collected for all patients who received at least one course of secukinumab. The retention rate was calculated using Kaplan-Meier method with log-rank test. Effectiveness was assessed at 6-month and at 12-month for inactive disease and for low disease activity states (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI < 2 and BASDAI < 4) and Ankylosing Spondylitis Disease Activity Score (ASDAS < 1.3 and ASDAS < 2.1). Results. The study included 616 patients with axial spondyloarthritis who received secukinumab. 226 patients were naïve to biologic treatments; 220 patients had one prior bDMARD; 170 patients used two or more bDMARDs. The overall 6-months and 12-months secukinumab retention rates were 68%/49% with significant differences in favour of biologic naïve patients: bDMARD-naïve: 78%/58%, 1 prior bDMARD: 63%/45%, ≥ 2 prior bDMARDs: 61%/41%. The 6-month and 12-month results for effectiveness: overall BASDAI < 2: 54%/66%; overall BASDAI < 4: 91%/97%; overall ASDAS < 1.3: 14%/19%; overall ASDAS < 2.1: 53%/73%. The number of previous bDMARDs had an impact on effectiveness, with more responders being observed in the biologic naïve group. Conclusions. Our results show that the best retention rate for secukinumab treatment, as well as efficacy, is attained for the bio-naive treatment group. The main reason for discontinuation of secukinumab treatment is secondary loss of efficacy

Objective. The study aimed to observe the variability of rheumatoid arthritis (RA) disease activity scores according to the type of patient global assessment (PtGA) and to compare these subjective assessments with objective measurements. Methods. Prospective study in which RA patients four types of assessments in the same day of their inclusion in the study: completing a questionnaire (including PtGA on a 100 mm visual analogue scale – VAS, and a 0-10 Likert scale), clinical interview and joint examination performed by each attending rheumatologist and peripheral venous blood sampling for acute phase reactants. Results. The study included 110 RA patients (57.5 years average age, 9.4 years median disease duration, 90.0% women, 58.2% in remission or low disease activity). There was low concordance and agreement between PtGA and physician global assessment (PhGA): the two evaluations were significantly but poorly correlated, and in 71.8% of cases VAS and Likert PtGA were higher than PhGA with at least 2 points in average. Patients with no tender or swollen joints (27.3%) reported a median VAS-PtGA of 27 cm and a median Likert-PtGA of 4.2 points. Likert-PtGA were higher than VAS-PtGA in the general sample and for patients with normal objective measures (patients in remission according to DAS28-3v-CRP reported a median VAS-PtGA of 5 points, compared to VAS-PtGA of only 2.2 cm). The strongest correlations of PtGA on both VAS and Likert scales were recorded for mHAQ (r = 0.521 and 0.589, p < 0.001), DAS28-3v-CRP (r = 0.419 and 0.422, p < 0.001) and the presence of prolonged morning stiffness (r = 0.361 and 0.485, p < 0.001). Conclusion. Romanian patients with RA seem to favour and understand the Likert scale better than the VAS when reporting PtGA.

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is responsible for the current pandemic, causing so far over 100.000 cases and more than 4500 deaths in Romania. Clinical manifestations are variable, ranging from mild forms (fever, dry cough, dyspnea, tachypnea, asthenia, myalgia) to severe bilateral pneumonia (COVID-19). Generally, patients with inflammatory/autoimmune rheumatic diseases have an increased risk of infections compared to the general population, especially if under treatment with immunosuppressive therapies. In the absence of infection or exposure to SARS-CoV-2, the use of specific drugs (non-steroidal anti-inflammatory drugs – NSAIDs; glucocorticoids - GC; conventional synthetic - csDMARDs, targeted synthetic – tsDMARDs and biologic disease-modifying anti-rheumatic drugs - bDMARDs, denosumab) should be unaffected. In patients with exposure to SARS-Co V-2, but without symptoms of COVID-19, NSAIDs, hydroxychloroquine, sulfasalazine and, in specific cases, IL-6 inhibitors may be continued, methotrexate, leflunomide, non-anti-IL-6 bDMARDs, tsDMARDs and immunosuppressants should be temporarily discontinued until a negative result for SARS-CoV-2 or for up to 2 weeks asymptomatic state for specific post-epidemiological COVID-19 symptoms. In patients with confirmed or suspected COVID-19 infection, non-anti-IL-6 bDMARDs, tsDMARDs, methotrexate, leflunomide, sulfasalazine and immunosuppressants must be temporarily discontinued. In such particular cases, IL-6 inhibitors and hydroxychloroquine may be continued, depending on the clinical context. In forms with severe respiratory manifestations, NSAIDs must be stopped. In all cases, non-essential medical consultations and maneuvers should be reduced where appropriate, with optimal use of telemedicine. Social distancing, facial masks and constant hand hygiene is advised for all patients, according to national and international recommendations.

The Romanian Register of Rheumatic Diseases (RRBR, in Romanian) is an electronic database which includes data regarding all patients with immune-mediated rheumatic diseases who receive biologic therapies. These real-life data include: demographics, clinical disease forms, comorbidities, treatment regimens with biologic disease-modifying anti-rheumatic drugs (bDMARDs), and efficacy and safety data related to these treatments. The purpose of this study was to analyse the data of patients with psoriatic arthritis (PsA) introduced in the RRBR in RRBR was relatively constant compared to previous years. Patients with PsA had numerous comorbidities, with cardiovascular being the most commonly encountered. Most patients continue to receive combination therapy with a conventional synthetic DMARD (csDMARD), methotrexate being the most commonly used, but the percentage was lower than 2018. The concomitant use of systemic glucocorticoids has been recorded at a very low percentage. There is a tendency to initiate biologic treatment earlier, with over one third of patients receiving biologic therapy within the first 2 years after diagnosis. The most prescribed bDMARDs are still TNF blockers, with etanercept (original + biosimilar) being the most common, followed by adalimumab (original + biosimilar). The only biologic agent with another mechanism of action that was reimbursed in Romania in 2019 was secukinumab, this drug being used in almost one third of initiation and being the main option in the case of switches. The efficacy data show that the vast majority of patients have a low disease activity or are in remission. Although the percentage of patients who had a tapering regimen was reduced, this strategy proved to be a valid option for the majority of those to which it was applied. RRBR is an extremely useful tool for evaluating real-life data related to patients with PsA and the therapeutic strategies used in Romania, allowing their integration and interpretation in the context of similar registers in other countries.

The number of rheumatoid arthritis (RA) patients with visits introduced in the Romanian Registry of Rheumatic Diseases (RRBR) has been steadily increasing within the last 3 years. Included patients display the classical phenotype of established RA, with a relatively high prevalence of extra-articular manifestations, cardiovascular comorbidity and a high burden regarding early retirement due to RA. Data regarding treatment showed a very low prevalence of monotherapy with biologic and targeted synthetic disease-modifying drugs (b/tsDMARD) and a low prevalence of glucocorticoid-therapy. Approximately a fifth of the patients started b/tsDMARD-therapy early during disease course (under 2 years from diagnosis). The most frequent prescribed bDMARD was etanercept, followed by adalimumab and rituximab. Treatment decisions trends in 2019 showed that some molecules present a negative balance, such as abatacept and rituximab, while others present a positive balance such as bDMARD biosimilars and tsDMARDs. Overall, b/tsDMARD achieved treatment target (DAS28-defined remission and LDA) within the first 6 months of treatment in 81.4% of treated patients. Also, RRBR data indicate a slow but significant increase in tapered regimens. Thus, the RRBR has proved to be a very valuable tool in capturing data regarding RA management in a real-life national setting of rheumatology healthcare.

The Romanian Registry of Rheumatic Diseases (RRBR, in Romanian) is an electronic application that includesdata of all patients with inflammatory rheumatic diseases treated with biologics in Romania. First patients with axial spondyloarthritis (axSpA) were included in 2015 and the registry collected multiple variables like demographics,axSpA therapies, disease activity, adverse events, in order to provide data for patients in our country. The number of axSpA patients introduced in RRBR has been steadily increasing within the last 3 years. Thepatients included in the registry are with the two types of ax SpA (non-radiographic and radiographic spondyloarthritis) with a relatively high prevalence of extra-scheletal manifestations and a lot of comorbidities. Dataregarding treatment showed a prevalence of monotherapy with biologic disease-modifying anti rheumatic drugs (bDMARDs), TNF-alpha inhibitors being used by 91% of the patients. 41% of the patients started bDMARD-therapy early during disease course (under 2 years from diagnosis). The most frequent prescribed bDMARDs wasadalimumab, followed by etanercept. Treatment decisions trends in 2019 showed that some molecules present a positive balance such as bDMARD biosimilars and secukinumab. Overall, bDMARDs achieved treatment target(ASDAS defined remission and LDA) within the first 6 months of treatment in 87.6% of treated patients. Also,RRBR data indicate a slow but significant increase in tapered regimens. Thus, the RRBR has proved to be avery valuable tool in capturing data regarding axial spondyloarthrits management in a real-life national setting ofrheumatology healthcare.

Given the limited resources of the health system, rheumatologists are interested in reducing the costs of modern treatments for rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis, given that the therapeutic targets are obtained and maintained. Data from the Romanian Registry of Rheumatic Diseases (RRBR, in Romanian) from 2016 to 2019 showed for all three diseases that: continuations on the same regimen with tapering experienced a marked increase; the yearly drug cost per patient steadily decreased towards 2019; adalimumab and etanercept originators present the most number of administrations per year and consequently the highest afferent costs in the entire observation period; new drugs (biologic biosimilars and targeted synthetic drugs) are gaining specific portions of the market; switches decrease costs of treatment since the hypothetical models in which switches would not have been performed and patients would have continued their previous treatment throughout the respective year showed 11% increases of costs. RRBR data have shown that reaching and maintaining therapeutic targets (including by switching strategies), reducing risks of adverse events by reducing exposure (tapering) and increasing the use of biosimilar biologics lead to significant cost reductions.

Background. The novel therapies in inflammatory rheumatic diseases have changed dramatically the evolution of these conditions, improving patient outcomes, as well as the quality of life. Nevertheless, the efficacy data continuously needs safety reports, on short and long term. Aim. The present study reports adverse events (AEs) captured by the Romanian Registry of Rheumatic Diseases (RRBR, in Romanian), during 2019. Methods. This observational study included all AEs reported in RRBR in 2019, the severity class, outcome and previous exposure to the therapeutic agent. Results. For the active cohort of 9,255 patients that had at least one visit during 2019, there have been 934 reported AEs: 568 cases for rheumatoid arthritis (RA) patients, 291 cases for ankylosing spondylitis (AS) patients and 75 cases for psoriatic arthritis (PsA) patients. The most prevalent AEs were infections, especially in RA patients. Of all AEs, 102 (11%) were serious AEs, with an equal impact of 11% in RA and AS groups. A number of 25 deaths were reported during the last year. Conclusion. AEs seem to be under-reported in the RRBR database, is accordance with literature data for registries which not do have a standardized method for AE reporting. This is an unmet need for safety data that also requires improving the knowledge about AE reporting requirements.