Diffusing Capacity of the Lungs for Carbon Monoxide and Echocardiographic Parameters in Identifying Mild Pulmonary Hypertension in the EUSTAR Cohort of Patients With Systemic Sclerosis.

BACKGROUND: The 2022 European Society of Cardiology/European Respiratory Society guidelines define pulmonary hypertension (PH) as a resting mean pulmonary artery pressure (mPAP) > 20 mm Hg at right heart catheterization (RHC). Previously, patients with an mPAP between 21 and 24 mm Hg were classified in a "gray zone" of unclear clinical significance. RESEARCH QUESTION: What is the diagnostic performance of the main parameters used for PH screening in detecting patients with systemic sclerosis (SSc) with an mPAP of 21 to 24 mm Hg at RHC? STUDY DESIGN AND METHODS: Patients with SSc from the European Scleroderma Trials and Research (EUSTAR) database with available tricuspid annular plane systolic excursion (TAPSE), systolic PAP (sPAP), and mPAP data were included. Patients with mPAP 21 to 24 mm Hg and patients with mPAP ≤ 20 mm Hg were considered for the analysis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. RESULTS: TAPSE/sPAP was lower in the group of patients with SSc with mPAP 21 to 24 mm Hg than in the non-PH group (0.58 [0.46-0.72] vs 0.69 [0.57-0.81] mm/mm Hg, respectively; P < .01). No difference was found in other parameters between the two groups. Diffusing capacity of the lungs for carbon monoxide < 80% of the predicted value had the highest sensitivity (88.9%) and NPV (80%), but the lowest specificity (18.2%) and PPV (30.8%) in detecting patients with SSc with mPAP 21 to 24 mm Hg. TAPSE/sPAP < 0.55 mm/mm Hg had the highest specificity (78.9%), PPV (50%), and accuracy (68.1%); its NPV was 75.4%, and its sensitivity was 45.1%. INTERPRETATION: In this study, diffusing capacity of the lungs for carbon monoxide < 80% of the predicted value was the parameter with the highest sensitivity and NPV in detecting patients with SSc with mPAP 21 to 24 mm Hg. TAPSE/sPAP < 0.55 mm/mm Hg had the highest specificity, PPV, and accuracy and, therefore, can be a useful additional parameter to decrease the number of unnecessary RHCs.

The Performance of Pulmonary Function Tests in Predicting Systemic Sclerosis-Interstitial Lung Disease in the European Scleroderma Trial and Research Database.

BACKGROUND AND OBJECTIVES: In SSc, ILD is a major cause of morbidity and mortality. We aimed to investigate the performance of DLCO (diffusing capacity of lung carbon monoxide) and FVC (forced vital capacity) delta change (Δ) and baseline values in predicting the development of SSc-ILD. METHODS: Longitudinal data of DLCO, FVC, and ILD on the HRCT of SSc patients from the EUSTAR database were evaluated at baseline (t0) and after 12 (±4) (t1) and 24 (±4) (t2) months. RESULTS: 474/17805 patients were eligible for the study (403 females); 46 (9.7%) developed ILD at t2. Positivity for anti-topoisomerase antibodies (117 patients) showed an association with ILD development at t2 (p = 0.0031). Neither the mean t0 to t1 change (Δ) of DLCO nor the mean t0 to t1 FVCΔ predicted the appearance of ILD at t2. Investigating the possible role of baseline DLCO and FVC values in predicting ILD appearance after 24 (±4) months, we observed a moderate predictive capability of t0 DLCO < 80%, stronger than that of FVC < 80%. CONCLUSIONS: We suggest that an impaired baseline DLCO may be predictive of the appearance of ILD after 2 years of follow-up. This result advances the hypothesis that a reduction in gas exchange may be considered an early sign of lung involvement. However, further rigorous studies are warranted to understand the predictive role of DLCO evaluation in the course of SSc.

An Insight on the Possible Association between Inflammatory Bowel Disease and Biologic Therapy with IL-17 Inhibitors in Psoriasis Patients.

Psoriasis is a chronic, inflammatory, multisystemic disease which affects approximately 2-3% of the population globally, whose onset is triggered by genetic and environmental factors which activate both dendritic cells and keratinocytes, resulting in the production of proinflammatory cytokines such as tumor necrosis factor alpha, interleukin 17, interleukin 23, interleukin 22, and interleukin 1ß. An in-depth understanding of the pathophysiology of psoriasis led to significant advances in the development of safe and efficient novel therapeutic options, with four classes of biologic therapy being approved for the management of moderate to severe psoriasis: tumor necrosis factor alpha inhibitors, interleukin 23 inhibitors, anti-interleukin 12/23 agents, anti-interleukin 17 agents, as well as small-molecule inhibitors, such as apremilast. Psoriasis is associated with comorbid conditions, namely psoriatic arthritis, cardiovascular disease, metabolic syndrome, psychiatric disorders, malignancy, as well as inflammatory bowel disease. For patients affected by both psoriasis and inflammatory bowel disease, there is a strong recommendation to avoid IL-17 inhibitors since they may play a part in the exacerbation of the gastrointestinal disease. Our aim was to perform a thorough literature review regarding the development of inflammatory bowel disease lesions in psoriasis patients treated with IL-17 inhibitors, along with a case presentation to emphasize the need for close follow-up of these patients.

Arrhythmias and Conduction Disturbances in Patients with Systemic Sclerosis-A Systematic Literature Review.

Systemic sclerosis (SSc) is an autoimmune disease characterized by skin and internal organ fibrosis and microvascular impairment, which can affect major organs, including the heart. Arrhythmias are responsible for approximately 6% of deaths in patients with SSc, and mainly occur due to myocardial fibrosis, which causes electrical inhomogeneity. The aim of this study was to determine the frequency of arrhythmias and conduction disturbances in SSc cohorts, and to identify the characteristics and risk factors associated with the occurrence of dysrhythmias in patients with SSc. A systematic literature review using PubMed, Embase, Web of Science and Scopus databases was performed. Full-text articles in English with arrhythmias as the main topic published until 21 April 2022 were included. Most prevalent arrhythmias were premature supraventricular and ventricular contractions, while the most frequent conduction disturbance was represented by right bundle branch block (RBBB). Elevated concentrations of N-terminal prohormones of brain natriuretic peptides (NT-pro BNP) were associated with numerous types of atrial and ventricular arrhythmias, and with the occurrence of RBBB. A lower value of the turbulence slope (TS) emerged as an independent predictor for ventricular arrhythmias. In conclusion, dysrhythmias are frequent in SSc cohorts. Paraclinical and laboratory parameters are useful instruments that could lead to early diagnosis in the course of the disease.

Performance of the New 2019 European Alliance of Associations for Rheumatology/American College of Rheumatology Systemic Lupus Erythematosus Classification Criteria in a Large Unicentric Cohort.

Background: The recently published 2019 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria for systemic lupus erythematosus (SLE) were developed to increase the reliability and identification of SLE, especially in early disease. With the emergence of several new drugs for SLE, identifying and treating patients early are more important than ever. Methods: Data of 446 SLE patients evaluated in our center between 1996−2019 and 226 controls with other autoimmune diseases evaluated between 2001−2022 were retrospectively analyzed. The sensitivity and specificity of the 2019 ACR/EULAR criteria were compared to the 2012 SLICC and the 1997 ACR criteria. Results: The 2019 ACR/EULAR criteria showed very good sensitivity (86.6%) compared to the 1997 ACR criteria (76.7%), p < 0.001, with a trend toward significance compared to the 2012 SLICC criteria (83.6%), p = 0.072. Their sensitivity remained high (87.6%) in patients with a short disease duration. The specificity of the 2019 ACR/EULAR criteria (91.2%) was statistically lower than the 2012 SLICC (96.0%) and 1997 ACR criteria (95.1%), p = 0.007 and p = 0.012, respectively, but still had a very high value. A total of 22 controls (9.7%) fulfilled at least one set of criteria (15 patients with MCTD, 5 with UCTD, and 2 with SSc). Conclusion: In this large real-life cohort, the 2019 ACR/EULAR criteria had very good performance compared to the 2012 SLICC and 1997 ACR criteria.

Effectiveness and safety of tocilizumab in patients with systemic sclerosis: a propensity score matched controlled observational study of the EUSTAR cohort.

OBJECTIVES: Tocilizumab showed trends for improving skin fibrosis and prevented progression of lung fibrosis in systemic sclerosis (SSc) in randomised controlled clinical trials. We aimed to assess safety and effectiveness of tocilizumab in a real-life setting using the European Scleroderma Trial and Research (EUSTAR) database. METHODS: Patients with SSc fulfilling the American College of Rheumatology (ACR)/EULAR 2013 classification criteria, with baseline and follow-up visits at 12±3 months, receiving tocilizumab or standard of care as the control group, were selected. Propensity score matching was applied. Primary endpoints were the modified Rodnan skin score (mRSS) and FVC at 12±3 months compared between the groups. Secondary endpoints were the percentage of progressive/regressive patients for skin and lung at 12±3 months. RESULTS: Ninety-three patients with SSc treated with tocilizumab and 3180 patients with SSc with standard of care fulfilled the inclusion criteria. Comparison between groups did not show significant differences, but favoured tocilizumab across all predefined primary and secondary endpoints: mRSS was lower in the tocilizumab group (difference -1.0, 95% CI -3.7 to 1.8, p=0.48). Similarly, FVC % predicted was higher in the tocilizumab group (difference 1.5 (-6.1 to 9.1), p=0.70). The percentage of progressive/regressive patients favoured tocilizumab over controls. These results were robust regarding the sensitivity analyses. Safety analysis confirmed previously reported adverse event profiles. CONCLUSION: Although this large, observational, controlled, real-life EUSTAR study did not show significant effectiveness of tocilizumab on skin and lung fibrosis, the consistency of direction of all predefined endpoints generates hypothesis for potential effectiveness in a broader SSc population.

Development and validation of a patient-reported outcome measure for systemic sclerosis: the EULAR Systemic Sclerosis Impact of Disease (ScleroID) questionnaire.

OBJECTIVES: Patient-reported outcome measures (PROMs) are important for clinical practice and research. Given the high unmet need, our aim was to develop a comprehensive PROM for systemic sclerosis (SSc), jointly with patient experts. METHODS: This European Alliance of Associations for Rheumatology (EULAR)-endorsed project involved 11 European SSc centres. Relevant health dimensions were chosen and prioritised by patients. The resulting Systemic Sclerosis Impact of Disease (ScleroID) questionnaire was subsequently weighted and validated by Outcome Measures in Rheumatology criteria in an observational cohort study, cross-sectionally and longitudinally. As comparators, SSc-Health Assessment Questionnaire (HAQ), EuroQol Five Dimensional (EQ-5D), Short Form-36 (SF-36) were included. RESULTS: Initially, 17 health dimensions were selected and prioritised. The top 10 health dimensions were selected for the ScleroID questionnaire. Importantly, Raynaud's phenomenon, impaired hand function, pain and fatigue had the highest patient-reported disease impact. The validation cohort study included 472 patients with a baseline visit, from which 109 had a test-retest reliability visit and 113 had a follow-up visit (85% female, 38% diffuse SSc, mean age 58 years, mean disease duration 9 years). The total ScleroID score showed strong Pearson correlation coefficients with comparators (SSc-HAQ, 0.73; Patient's global assessment, Visual Analogue Scale 0.77; HAQ-Disability Index, 0.62; SF-36 physical score, -0.62; each p<0.001). The internal consistency was strong: Cronbach's alpha was 0.87, similar to SSc-HAQ (0.88) and higher than EQ-5D (0.77). The ScleroID had excellent reliability and good sensitivity to change, superior to all comparators (intraclass correlation coefficient 0.84; standardised response mean 0.57). CONCLUSIONS: We have developed and validated the EULAR ScleroID, which is a novel, brief, disease-specific, patient-derived, disease impact PROM, suitable for research and clinical use in SSc.

Screening for Pulmonary Hypertension in Systemic Sclerosis-A Primer for Cardio-Rheumatology Clinics.

Systemic sclerosis (SSc) is a rare disease, with unfavorable clinical course and prognosis, characterized by progressive multisystemic involvement. SSc associated pulmonary hypertension (SSc-PAH) and interstitial lung disease (ILD) are the most important factors for morbi-mortality in these patients, being responsible for more than 60% of total deaths. Though pulmonary arterial hypertension (PAH) is the dominant subtype seen in SSc, PH secondary to ILD, left-heart pathology, and pulmonary veno-occlusive disease (PVOD) are also possible occurrences. Initial evaluation of a SSc case is complex and should be performed with a multidisciplinary approach. Early detection of SSc-PAH is imperative, given the fact that new and effective medications are available and early treatment was shown to improve outcomes. Therefore, screening algorithms must be used adequately and in a cost-effective manner. Sensitivity and negative predictive value (NPV) are the most important performance measures in a screening test. Several algorithms were developed in the last decade (e.g., DETECT and ASIG) and demonstrated higher efficiency when compared to older algorithms. The present manuscript details the risk factors for SSc-PAH and includes a critical description of current detection algorithms, as a primer for clinicians working in the field of cardio-rheumatology.

Reliability, Validity, and Sensitivity to Change of the Cochin Hand Functional Disability Scale and Testing the New 6-Item Cochin Hand Functional Disability Scale in Systemic Sclerosis.

Systemic sclerosis (SSc) is a chronic autoimmune disease causing complex hand disability. A reliable tool for hand function assessment in SSc is the Cochin Hand Functional Disability Scale (CHFS). More recently, a short-form CHFS of 6 items (CHFS-6) has been developed. OBJECTIVES: To validate the CHFS and the new CHFS-6 in Romanian patients with SSc. PATIENTS AND METHODS: Consecutive patients with SSc who completed the CHFS were included. All patients were assessed according to the recommendations of the European Scleroderma and Research Trials and also completed the Scleroderma Health Assessment Questionnaire and the Hand Mobility in Scleroderma questionnaire. Finger range-of-motion distances were measured. RESULTS: Seventy patients, 63 female and 7 male patients (age median, 53.0 years; interquartile range [IQR], 21.0 years), were included. Twenty seven had diffuse cutaneous involvement (dcSSc). Median CHFS and CHFS-6 at baseline were 25.0 (IQR, 37.0) and 8.0 (IQR, 13.0), respectively.The internal consistency (Cronbach α = 0.96, respectively, 0.90, in all 70 patients) and test-retest reliability (intraclass correlation coefficient = 0.98 for both, in 38 patients) of both CHFS and CHFS-6 were excellent. The CHFS-6 had a very high correlation with the CHFS. There were moderate to good correlations with Hand Mobility in Scleroderma, Scleroderma Health Assessment Questionnaire, and the anthropometric measurements (construct validity). In patients with early dcSSc with a second evaluation, we found good to moderate sensitivity to change (standardized response mean of 0.8 and effect size of 0.4 for CHFS, and standardized response mean of 1.1 and effect size of 0.6 for CHFS-6). CONCLUSIONS: The CHFS and CHFS-6 are valid and easy-to-use tools for hand involvement in SSc, which can be used in clinical or research setting.

Capillary loss reflects disease activity and prognosis in patients with systemic sclerosis.

Capillary density on nailfold capillaroscopy (NFC) is considered a promising instrument for assessing disease characteristics in patients with systemic sclerosis (SSc), however, there is no agreement yet over how to analyze and interpret the results. The objective of this study was to investigate the possible associations of the mean number of capillaries with disease characteristics, disease activity [measured by the European Scleroderma Study Group (EScSG) disease activity score] and survival in a single-center cohort of patients with SSc. Sixty-eight patients were included; 54 had follow-up at 6 months. Thirty-two images per patient were assessed independently by two raters, scoring the mean number of capillaries in all fingers (N), in the 3rd finger of the dominant hand (dN3) and in the 4th finger of the non-dominant hand (ndN4) for each patient. NFC 'early', 'active' and 'late' patterns were also assessed. Two thousand and seventy-six images were scored at baseline, 1,728 at follow-up. Baseline N was median (IQR) 5.1 (2.7) for rater 1, and 4.9 (1.7) for rater 2, respectively. N was significantly lower in patients with a history of digital ulcers (DUs), vs. those who never had DUs 4.8 (1.4) vs. 6.4 (3.1), P=0.016. A lower N was associated with higher disease activity at baseline and follow-up (linear regression adjusted for age, sex and history of DUs). A lower ndN4 was associated with increased mortality (logistic regression adjusted for age and sex). In conclusion, in patients with SSc, a lower mean number of capillaries assessed by NFC was associated with higher disease activity after 6 months of follow-up and with shorter survival.

Digital ulcer debridement in systemic sclerosis: a systematic literature review.

Optimal wound care is an essential component in the management of systemic sclerosis (SSc) digital ulcers (DUs). DU debridement has been suggested to reduce ulcer-related pain and improve tissue healing. However, only a minority of rheumatologists perform DU debridement, and there is no standard of care/protocol. Our objectives were to (i) evaluate the current evidence for the use of debridement in DU management and (ii) assess whether there are any specific protocols. A systematic literature review was performed searching the PubMed database (between 01/01/1950-01/03/2019) in accordance with PRISMA guidelines. Two independent reviewers screened and extracted the abstracts/full manuscripts. Articles in English, which focussed on SSc-DU debridement/curettage, were included. Exclusion criteria included studies of juvenile/paediatric patients and basic/non-clinical research. Our search identified 1497 studies of which 4 studies were included in our final analysis. Three studies used scalpel debridement, and one study used this in combination with autolytic debridement. No studies specifically reported the effect on DU healing from debridement. Autolytic debridement with hyaluronate-based products was associated with significant ulcer pain and inflammation. Local anaesthetic significantly reduces pain both during and after debridement. Combined local and oral analgesia is often required for more severe or infected DUs. DU (scalpel and autolytic) debridement is being used by some clinicians in rheumatology; however, there are no standardised protocols. To improve wound care for SSc-DUs, future research should focus on developing a standardised protocol for SSc-DU debridement, with a view to facilitate randomised controlled trials to demonstrate safety and treatment efficacy.Key Points• Optimal wound care is an essential component in the management of systemic sclerosis-digital ulcers.• 'Sharp' debridement uses a scalpel, whereas 'autolytic' debridement uses dressings to optimize endogenous tissue lysis.• There is significant variation in the use of digital ulcer debridement in systemic sclerosis.• A standardized protocol and randomized controlled trials are needed to demonstrate debridement the safety and efficacy of digital ulcer debridement in systemic sclerosis.

Incidence and risk factors for gangrene in patients with systemic sclerosis from the EUSTAR cohort.

OBJECTIVE: In patients with SSc, peripheral vasculopathy can promote critical ischaemia and gangrene. The aim of this study was to investigate the prevalence, incidence and risk factors for gangrene in the EUSTAR cohort. METHODS: We included patients from the EUSTAR database fulfilling the ACR 1980 or the ACR/EULAR 2013 classification criteria for SSc, with at least one visit recording data on gangrene. Centres were asked for supplementary data on traditional cardiovascular risk factors. We analysed the cross-sectional relationship between gangrene and its potential risk factors by univariable and multivariable logistic regression. Longitudinal data were analysed by Cox proportional hazards regression. RESULTS: 1757 patients were analysed (age 55.9 [14.5] years, disease duration 7.9 [10.3] years, male sex 16.7%, 24.6% diffuse cutaneous subset [dcSSc]). At inclusion, 8.9% of patients had current or previous digital gangrene, 16.1% had current digital ulcers (DUs) and 42.7% had ever had DUs (current or previous). Older age, DUs ever and dcSSc were statistically significant risk factors for gangrene in the cross-sectional multivariable model. During a median follow-up of 13.1 months, 16/771 (0.9%) patients developed gangrene. All 16 patients who developed gangrene had previously had DUs and gangrene. Further risk factors for incident gangrene were the dcSSc subset and longer disease duration. CONCLUSION: In unselected SSc patients, gangrene occurs in about 9% of SSc patients. DUs ever and, to a lesser extent, the dcSSc subset are strongly and independently associated with gangrene, while traditional cardiovascular risk factors could not be identified as risk factors.

Patient-reported outcome instruments in clinical trials of systemic sclerosis.

Patient-reported outcome instruments provide valuable insight into disease-related morbidity known only to the patient and complement more objective outcome tools in the clinical trial setting. They are of particular importance in systemic sclerosis owing to the challenges around defining disease activity, the episodic nature of many disease-specific manifestations and the paucity of validated objective surrogate outcome measures for use in clinical trials. Early clinical trials of systemic sclerosis often incorporated legacy patient-reported outcome instruments, but the last 20 years has witnessed the emergence of several scleroderma-specific instruments that are now being routinely used alongside other outcomes in systemic sclerosis clinical trials. More recently, the value of patient-reported outcomes has been highlighted by their prominence in the American College of Rheumatology Combined Response Index for Systemic Sclerosis that has been utilized as the primary endpoint of recent clinical trials of early diffuse systemic sclerosis. This review considers the role and performance of the various patient-reported outcome instruments utilized in systemic sclerosis clinical trials, the current positioning of patient-reported outcome instruments within clinical trial endpoint models across the range of systemic sclerosis disease manifestations and, where applicable, we shall highlight areas for future research.

The emerging application of semi-quantitative and quantitative capillaroscopy in systemic sclerosis.

Systemic sclerosis (SSc) is a connective tissue disease with high morbidity and mortality, characterized by autoimmunity, obliterative vasculopathy involving mainly the microvasculature, and fibrosis. SSc-specific nailfold capillaroscopic changes have been defined, and nailfold capillaroscopy (NFC) is now unequivocally accepted to be a cornerstone for the early diagnosis of SSc. However, the use of NFC in patients already diagnosed with SSc is still not standardized. Several studies have shown that NFC abnormalities correlate with disease activity and severity and are predictive for disease worsening, such as occurrence of new digital ulcers. More importantly, successful treatment has been shown to diminish NFC abnormalities in severe SSc cases. These findings support the importance of NFC in monitoring patients with SSc and even its role as an outcome measure in SSc clinical trials. It is a matter of debate if Semi-quantitative and Quantitative NFC would be a more sensitive tool than qualitative NFC for meeting these objectives. This review is presenting the emerging application of Semi-quantitative and Quantitative NFC in SSc and its potential benefits.

Cutting Edge: Homeostasis of Innate Lymphoid Cells Is Imbalanced in Psoriatic Arthritis.

Innate lymphoid cells (ILC) have a high potency for cytokine production independent of specific Ag stimulation. Imbalance of ILC subsets may influence cytokine production in humans and hence be associated with the development of inflammatory disease. Evidence for an imbalance of ILC homeostasis in human disease, however, is very limited to date. In this study we show that psoriatic arthritis (PsA), a severe disease of the joints depending on the activation of the IL-23/IL-17 pathway, is characterized by a skewed ILC homeostasis. Circulating ILC3s as potent source of IL-17/IL-22 were elevated in active PsA, whereas ILC2s, which produce proresolving cytokines, were decreased. The ILC2/ILC3 ratio was significantly correlated with clinical disease activity scores and the presence of imaging signs of joint inflammation and bone damage. Multivariable analysis showed that a high ILC2/ILC3 ratio is associated with remission in PsA, suggesting that specific alterations of ILC homeostasis control disease activity in PsA.

Risk of active tuberculosis in patients with inflammatory arthritis receiving TNF inhibitors: a look beyond the baseline tuberculosis screening protocol.

Tuberculosis (TB) is a major concern in patients receiving TNF inhibitors (TNFi). This study aimed to assess the incidence of active TB and the efficacy of TB prevention measures used over the years, and to determine risk factors for developing TB, in a single-centre cohort of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) receiving TNFi. Data of all patients in whom treatment with TNFi was initiated in our rheumatology clinic until December 1st 2014 have been retrospectively analysed. The cohort was divided into 3 groups per the mandatory LTBI screening method at baseline: tuberculin skin test (TST) with a positive threshold of either 10 mm (group TST1), or 5 mm (group TST2), and QuantiFERON®-TB Gold test (group QFT). The incidence of active TB was analysed for each group and compared to TB incidence data in general population. Five hundred fifty patients were included (305 RA, 42 PsA, 203 AS); 97 patients belonged to the TST1, 229 to the TST2 and 224 to the QFT group. The number of active TB cases/time of exposure to TNFi (person-years, PY) was 8/593.5, 9/1044.0 and 3/555.3, respectively, accounting for an incidence of 1348.0, 862.1 and 540.2 cases per 105 PY. Active TB cases occurring in the first year of TNFi treatment (early TB) per total TB cases were only 3/8, 1/9 and 1/3, respectively, too few to identify statistically significant differences between the 3 LTBI screening protocols. However, less TB cases per total observation time were registered in the QFT group, probably due to the reduced duration of exposure to TNFi. All cases of active TB were registered among patients receiving monoclonal antibodies TNFi agents. We have found no significant risk factors for developing active TB. In our cohort, TB occurring after 1 year of TNFi treatment exceeds 'early TB', suggesting the necessity of further TB prevention measures besides baseline screening for LTBI.