IL-1 Inhibitors in the Treatment of Familial Mediterranean Fever: Treatment Indications and Clinical Features in a Large Real-World Cohort.

Background: The accruing evidence about the efficacy of anti-IL-1 agents in Familial Mediterranean Fever (FMF) patients led to their widespread off-label use. Therefore, identifying precise indications and clinical characteristics of IL-1i-warranting patients are important. This study investigated the clinical characteristics and treatment indications of patients with FMF requiring interleukin 1 inhibition therapy (IL-1i). Methods: Hospital records of FMF patients attending a tertiary care center at the Department of Rheumatology, University of Health Sciences, Basaksehir Cam and Sakura City Hospital were retrospectively analyzed. Data on symptoms and disease manifestations, age of symptom onset, time to diagnosis, MEFV variants, type of treatment, and their indications were collected. Results: Between June 2020 and March 2023, 312 FMF patients were identified. The mean age at the onset of symptoms was 14.0, and the mean time to diagnosis was 11.9 years. In total, 87.1% of patients were receiving colchicine monotherapy, while the remaining 11.8% warranted IL-1i. Clinical symptoms and flare manifestations did not show a significant difference between the two groups. However, patients receiving IL-1i started having symptoms at younger age (11.5 vs. 14.5, p = 0.042) and time to diagnosis was longer (18.2 vs. 11.0, p < 0.01). M694V homozygosity was more common in patients receiving IL-1i. Indications for patients receiving IL-1i were colchicine resistance (8.0%), secondary amyloidosis (5.1%), and colchicine intolerance (2.2%). Conclusions: This study shows that a subset of FMF patients, particularly those with a more severe phenotype with an earlier disease onset and M694V homozygosity, require IL-1i treatment despite the overall good efficacy and tolerability of colchicine, primarily due to colchicine resistance, intolerance, or complications such as amyloidosis.

Tocilizumab as a first line biologic agent in rheumatoid arthritis patients with inadequate response to disease-modifying anti-rheumatic drugs: real life experience from the TReasure Registry.

OBJECTIVES: To evaluate the retention rate, treatment response and safety of tocilizumab (TCZ) as first-line biologic treatment in rheumatoid arthritis (RA) patients with inadequate response to disease-modifying anti-rheumatic drugs (DMARD-IR). METHODS: The TReasure Registry is a multicentre, web-based registry of RA and spondyloarthritis patients across Turkey. DMARD-IR RA patients who received TCZ as first-line biologic treatment were included in this registry for efficacy and safety. Demographic and clinical data, treatments, and adverse events were collected. Drug retention rate was estimated using Kaplan-Meier analysis. RESULTS: Among 642 RA patients who ever used TCZ, 258 DMARD-IR RA patients (male/female: 18.2%/81.8%, mean age, 54.41 years) received TCZ as first-line biologic. The median disease duration was 97 (range, 60-179) months and the median TCZ treatment duration was 15 (range, 6-28) months. At the 6th and 12th months of TCZ treatment, the decrease in disease activity scores from baseline was significant. The Kaplan-Meier analysis revealed the retention rate of TCZ at the 12th, 24th, 36th, and 60th months as 81.1%, 73.8%, 66.2%, and 63.6%, respectively. Fifty-seven (22%) patients discontinued TCZ; the main reason being primary or secondary inefficacy (n=29). CONCLUSIONS: Over 80% drug retention rate at 12th month of TCZ treatment in this real-world study was concordant with previously conducted TCZ clinical studies. Significant reductions not only in the disease activity score-28 but also in the simplified disease activity index (SDAI) and clinical disease activity index (CDAI) scores, along with health assessment questionnaire (HAQ) scores, supported the impact of TCZ in RA management with a good safety profile.

Treatment of systemic sclerosis-associated digital ulcers: recommendations of the Turkish Society for Rheumatology.

OBJECTIVES: Digital ulcers (DUs) are associated with a significant burden in systemic sclerosis (SSc) by leading to severe pain, physical disability, and reduced quality of life. This effort aimed to develop recommendations of the Turkish Society for Rheumatology (TRD) on the management of DUs associated with SSc. METHODS: In the first meeting held in December 2020 with the participation of a task force consisting of 23 rheumatologists the scope of the recommendations and research questions were determined. A systematic literature review was conducted by 5 fellows and results were presented to the task force during the second meeting. The Oxford system was used to determine the level of evidence. The preliminary recommendations were discussed, modified, and voted by the task force and then by members of TRD via e-mail invitation allowing personalised access to a web-based questionnaire [SurveyMonkey®]. RESULTS: A total of 23 recommendations under 7 main headings were formulated covering non-pharmacological measures for the prevention of DUs and pharmacological treatments including vasodilators, anti-aggregants, antibiotics, wound care, pain control, and interventions including sympathectomy, botulinum toxin, and surgery. Risk factors, poor prognostic factors, prevention of DU and adverse effects of medical treatments were reported as 4 overarching principles. CONCLUSIONS: These evidence-based recommendations for the management of SSc-associated DUs were developed to provide a useful guide to all physicians who are involved in the care of patients with SSc, as well as to point out unmet needs in this field.

Pulmonary involvement in antineutrophil cytoplasmic antibody-associated vasculitides: A single center experience from Turkey.

OBJECTIVE: Pulmonary involvement is an important cause of mortality and morbidity in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). In this study, we aimed to evaluate the type and frequency of pulmonary involvement and investigate the potential relationship between thorax computed tomography (CT) signs and other systemic clinical findings in AAV. METHODS: A total of 63 patients over the age of 18 and diagnosed with AAV were included in this study. Thoracic CT imaging findings and clinical features of the patients at the time of diagnosis were retrospectively evaluated. The frequency and distribution of detected pathological findings on imaging according to disease types, in addition to the relationship of these findings with other systemic findings and disease severity, were analyzed. RESULTS: Of 63 patients, 50 (79.4%) had pulmonary symptoms at the time of presentation. Most frequently observed pulmonary finding of thorax CT was nodular opacity. Consolidation, cavitary nodules, bronchiectasis, emphysema and fibrotic sequelae change were more common in the patients with diagnosis of granulomatosis with polyangiitis. Honeycomb, atelectasis, interstitial pneumonia, pulmonary venous congestion and pleural effusion were more common in the patients with diagnosis of microscopic polyangiitis. Ground-glass appearance, central airway disease, peribronchovascular nodules, pericardial effusion and lymphatic adenomegaly (>10 mm) were more common in the patients with diagnosis of eosinophilic granulomatosis with polyangiitis. Interstitial lung disease, pulmonary hemorrhage and severe lung involvement were found significantly increased in patients with myeloperoxidase antibody (MPO)-ANCA positivity (P < 0.05). CONCLUSION: Lung involvement was detected in almost all of the patients with AAV. Both interstitial lung disease and severe lung involvement were more frequently found in patients with MPO-ANCA positivity compared to other patients. Pulmonary examination by an imaging technique in all patients with AAV may be useful to determine the vasculitis subtype and to determine the extent of the disease. PRACTITIONER POINTS: Pulmonary involvement is quite common in AAV. Every patient with suspected AAV should be examined with imaging for lung involvement, even in the absence of respiratory symptoms. Severe pulmonary involvement is associated with the presence of severe disease and MPO-ANCA positivity.

Evaluation of the Optic Nerve Head Using Optical Coherence Tomography Angiography in Systemic Sclerosis Patients.

PURPOSE: To quantify microvascular vessel density in the optic disc using optical coherence tomography angiography (OCTA) in patients with systemic sclerosis (SS); to determine whether there is a difference in values between patients and controls; and to correlate the OCTA measurements with disease activity, damage risk, and drug usage. METHODS: Patients aged 20 - 76 years who were followed up after a diagnosis of SS and age- and gender-matched controls. The patients underwent RTVue-XR AngioVue OCTA imaging in this cross-sectional observational study. RESULTS: A total of 61 eyes of 61 consecutive SS patients and 60 eyes of 60 controls were investigated. There was no statistically significant difference between the patients and control groups regarding the average RNFL (retinal fiber layer) and radial peripapillary capillary (RPC) vessel density (VD) measurements (p = 0.35, p = 0.25, respectively). As the antinuclear antibody (ANA) titer increased, RNFLsuperior (p = 0.01, r = - 0.327), RPCwhole (p = 0.029, r = 0.279), RPCperipapillary (p = 0.037, r = - 0.267), RPCsuperior (p = 0.003, r = - 0.371), and RPCinferior (p = 0.02, r = 0.297) values decreased with statistical significance. The RPCinside values were lower in anti-Scl-70-positive patients compared to patients negative for anti-Scl-70 (topoisomerase I) (p = 0.021). The RNFLnasal (p = 0.03, r = - 0.278) value decreased as the years of disease increased. The RPCinside value was higher in patients using hydroxychloroquine and calcium channel blockers than those who did not use them (p = 0.021 and p = 0.027, respectively). The RPCwhole, RPCperipapillary, and RPCnasal values were higher, with statistical significance in corticosteroid users than in those patients who did not use corticosteroids (p = 0.043, 0.030, and 0.033, respectively). CONCLUSION: There was no significant difference between the patients and control groups regarding the average RPC VD measurements. However, since this is the first study to analyze optic disc vessel density in SS patients, optic nerve blood flow changes in scleroderma with OCTA could be studied.

Antifibrotic therapies in rheumatoid arthritis associated interstitial lung disease.

Interstitial lung disease (ILD) is one of the common extra-articular manifestations of rheumatoid arthritis (RA) and it is associated with high mortality rate. The usual interstitial pneumonia (UIP) pattern of RA associated ILD (RA-ILD) shows some similarities to idiopathic pulmonary fibrosis, suggesting that antifibrotic therapies may have potential positive affects. In this review, we discuss the effectiveness of antifibrotic therapy for RA-ILD.

Palpable purpura: is it associated with vasculitis or not? A single-center experience.

BACKGROUND AND AIM: The most common cutaneous manifestation of small vessel vasculitis is palpable purpura. Etiology includes various causes such as infections, malignancies, drugs, and systemic vasculitides. The number of studies that evaluated the etiology of patients presenting with palpable purpura in the adult age group is minimal. This study aimed to determine the etiology in patients presenting with palpable purpura and analyze the clinical features associated with this pathology. MATERIALS AND METHODS: We included 85 patients over 18 years old who presented with palpable purpura in the study. The presenting demographic characteristics, medical history, systemic examination findings, laboratory, imaging, and histopathological results, and initial treatment of the patients were recorded. At the end of data collection, statistical analyses were performed to determine the patients' final diagnoses and organ involvement. RESULTS: Etiological evaluation revealed Ig A vasculitis (IgAV) in 58.8% (n = 50) of the cases, cutaneous leukocytoclastic vasculitis (CLV) in 23.5% (n = 20), and ANCA-associated vasculitis (AAV) in 3.5% (n = 3). Rheumatologic disease-associated vasculitis (RDaV) was detected in 7.1% (n = 6) of the patients. In 7.1% (n = 6) of the patients, the biopsy results were not compatible with vasculitis (NVH). DISCUSSION: Palpable purpura can occur due to many reasons. Ig A vasculitis was the most common cause of palpable purpura in our study. KEY POINTS: • All clinicians should recognize and know palpable purpura and its differential diagnosis. • IgA vasculitis is the most common cause of palpable purpura in adult patients. • In our study, Anca-associated vasculitis (AAV) was found in 3 (3%) of 85 adult patients with palpable purpura.

Tocilizumab treatment in severe COVID-19: a multicenter retrospective study with matched controls.

Coronavirus disease-2019 (COVID-19) associated pneumonia may progress into acute respiratory distress syndrome (ARDS). Some patients develop features of macrophage activation syndrome (MAS). Elevated levels of IL-6 were reported to be associated with severe disease, and anti-IL-6R tocilizumab has been shown to be effective in some patients. This retrospective multicenter case-control study aimed to evaluate the efficacy of tocilizumab in hospitalized COVID-19 patients, who received standard of care with or without tocilizumab. Primary outcome was the progression to intubation or death. PSMATCH (SAS) procedure was used to achieve exact propensity score (PS) matching. Data from 1289 patients were collected, and study population was reduced to 1073 based on inclusion-exclusion criteria. The composite outcome was observed more frequently in tocilizumab-users, but there was a significant imbalance between arms in all critical parameters. Primary analyses were carried out in 348 patients (174 in each arm) after exact PS matching according to gender, ferritin, and procalcitonin. Logistic regression models revealed that tocilizumab significantly reduced the intubation or death (OR 0.40, p = 0.0017). When intubation is considered alone, tocilizumab-users had > 60% reduction in odds of intubation. Multiple imputation approach, which increased the size of the matched patients up to 506, provided no significant difference between arms despite a similar trend for intubation alone group. Analysis of this retrospective cohort showed more frequent intubation or death in tocilizumab-users, but PS-matched analyses revealed significant results for supporting tocilizumab use overall in a subset of patients matched according to gender, ferritin and procalcitonin levels.

ANCA Associated Vasculitis and Related Pulmonary Alveolar Hemorrhage in a Patient with Pulmonary Alveolar Proteinosis.

ABSTRACT: Pulmonary Alveolar Proteinosis (PAP) is a rare lung disease characterized by accumulation of a lipoproteinous material in the alveoli and distal airways. Antibodies against granulocyte macropha-ge colony stimulant factor (GM-CSF) are thought to be responsible for its pathogenesis. Antineutrophilic cytoplasmic antibody (ANCA) associated vasculitis (AAV) is a group of vasculitis affecting small and medium vessels and often characterized by lung and kidney involvement. Here, we present a patient with PAP diagnosis who has been in remission for many years, developing AAV and associated pulmonary alveolar hemorrhage. Pulmonary Alveolar Proteinosis (PAP) is a rare lung disease characterized by accumulation of a lipoproteinous material in the alveoli and distal airways. Antibodies against granulocyte macropha-ge colony stimulant factor (GM-CSF) are thought to be responsible for its pathogenesis. Antineutrophilic cytoplasmic antibody (ANCA) associated vasculitis (AAV) is a group of vasculitis affecting small and medium vessels and often characterized by lung and kidney involvement. Here, we present a patient with PAP diagnosis who has been in remission for many years, developing AAV and associated pulmonary alveolar hemorrhage.

COVID-19 Among Patients With Inflammatory Rheumatic Diseases.

BACKGROUND: The course of novel coronavirus disease 2019 (COVID-19) has been of special concern in patients with inflammatory rheumatic diseases (IRDs) due to the immune dysregulation that may be associated with these diseases and the medications used for IRDs, that may affect innate immune responses. OBJECTIVE: In this cohort study, we aimed to report the disease characteristics and variables associated with COVID-19 outcome among Turkish patients with IRDs. METHODS: Between April and June, 2020, 167 adult IRD patients with COVID-19 were registered from 31 centers in 14 cities in Turkey. Disease outcome was classified in 4 categories; (i) outpatient management, (ii) hospitalization without oxygen requirement, (iii) hospitalization with oxygen requirement, and (iv) intensive care unit (ICU) admission or death. Multivariable ordinal logistic regression analysis was conducted to determine variables associated with a worse outcome. RESULTS: 165 patients (mean age: 50 ± 15.6 years, 58.2% female) were included. Twenty-four patients (14.5%) recovered under outpatient management, 141 (85.5%) were hospitalized, 49 (30%) required inpatient oxygen support, 22 (13%) were treated in the ICU (17 received invasive mechanic ventilation) and 16 (10%) died. Glucocorticoid use (OR: 4.53, 95%CI 1.65-12.76), chronic kidney disease (OR: 12.8, 95%CI 2.25-103.5), pulmonary disease (OR: 2.66, 95%CI 1.08-6.61) and obesity (OR: 3.7, 95%CI 1.01-13.87) were associated with a worse outcome. Biologic disease-modifying antirheumatic drugs (DMARDs) do not seem to affect COVID-19 outcome while conventional synthetic DMARDs may have a protective effect (OR: 0.36, 95%CI 0.17-0.75). Estimates for the associations between IRD diagnoses and outcome were inconclusive. CONCLUSIONS: Among IRD patients with COVID-19, comorbidities and glucocorticoid use were associated with a worse outcome, while biologic DMARDs do not seem to be associated with a worse outcome.

Favorable retention rates and safety of conventional anti-rheumatic drugs in older patients with rheumatoid arthritis.

Physicians are challenged by the recognition and treatment of older patients with rheumatoid arthritis (RA). The aim of this case-control study was to evaluate the retention and safety of conventional disease-modifying anti-rheumatic drugs in older patients with RA.In this observational case-control study, we assessed older patients with RA (≥65 years) who were diagnosed in 3 different rheumatology centers from Turkey. Patients were divided as to those aged ≥65 years (elderly rheumatoid arthritis [ERA]) and those aged <65 years (young rheumatoid arthritis [YRA]) at the time of conventional DMARD treatment initiation. The Mann-Whitney U test was used for the comparison of 2 non-normally distributed groups. The Chi-square (χ) test was used for categorical variables. Survival analysis were performed using the Kaplan-Meier method.Four hundred eighteen patients with RA (296 females [71%]) were included from January 2010 to January 2018. The age of treatment onset of 190 (47%) patients was in the elderly period and they were included in the ERA group. In the analysis of drug retention rates, there was no significant difference between the ERA and YRA groups for each conventional DMARD (methotrexate 71.2% in ERA, 62.7% in YRA, P = .817; hydroxychloroquine 82.9% in ERA, 78.8% in YRA, P = .899; leflunomide 81.4% in ERA, 84.4% in YRA, P = .205; sulfasalazine 37.5% in ERA, 40.9% in YRA, P = .380). The adverse event data were also similar in both groups.The drug retention and adverse effect rates in older patients with RA using conventional DMARDS are similar to the rates in young patients with RA.