Rheumatoid factor titers, but not Fc fragments, may be strongly associated with drug survival of anti-TNF agents in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the effects of both the Fc fragment in tumor necrosis factor (TNF) inhibitors and rheumatoid factor (RF) titers on treatment survival, disease activity, and laboratory parameters in patients with rheumatoid arthritis (RA). METHODS: In this retrospective cohort study, patients with RA who had started any anti-TNF therapy between January 2017 and March 2020 and who had stayed on this treatment for at least six months were included. The data of the patients were compared separately according to continuation or discontinuation of treatment and the presence or absence of Fc portion in the structure of anti-TNFs. Patients who were taking certolizumab pegol (CZP) without the Fc fragment were placed in the "without Fc group" (wo/Fc), while patients who were taking other drugs (adalimumab, etanercept, golimumab, and infliximab) were placed in the "with Fc group" (w/Fc). RESULTS: Among the 221 RA patients whose data were available, 52 patients met the inclusion criteria and were included in the study. There was a significant difference in the DAS28-CRP score between wo/Fc group and w/Fc group in the third month of treatment (p=0.012). However, this difference did not persist at the sixth month of treatment (p=0.384). According to the cox-regression results, RF titers were determined to have a significant impact on the drug survival of anti-TNF agents when adjustments were made for the effects of other candidate predictors (Hazard ratio: 1.007 (1.002-1.012), p=0.009). CONCLUSION: Our results suggest that compared to the Fc fragment, RF titers were the more important risk factor in survival of anti-TNF drugs.

Familial Mediterranean fever: perspective on female fertility and disease course in pregnancy from a multicenter nationwide network.

The aim of this study was to analyze the pregnancy process, especially the Familial Mediterranean fever (FMF) disease course and attack types during pregnancy, and to examine the relationship between disease-related factors and female infertility in FMF patients. The study, which was planned in a multicenter national network, included 643 female patients. 435 female patients who had regular sexual intercourse were questioned in terms of infertility. Pregnancy and delivery history, FMF disease severity and course during pregnancy were evaluated. The relationship between demographic and clinical findings, disease severity, genetic analysis results and infertility was investigated. 401 patients had at least 1 pregnancy and 34 patients were diagnosed with infertility. 154 patients had an attack during pregnancy. 61.6% of them reported that attacks during pregnancy were similar to those when they were not pregnant. The most common attack symptoms were fever, fatigue and abdominal pain-peritonitis (96%, 87%, and 83%, respectively) in the pregnancy period. The disease-onset age, disease activity score, gene mutation analyses, and regular colchicine use (> 90%) were similar between the fertile and infertile groups, while the frequency of previous appendectomy and alcohol consumption rates were higher in individuals with infertility. Our results indicated no significant change in the frequency and severity of attacks during pregnancy. The low rate of infertility (7.8%) in our patients was noted. It has been suggested that the risk of FMF-related infertility may not be as high as thought in patients who are followed up regularly and received colchicine.

The effect of central sensitization on disease activity measures, quality of life and clinical parameters in axial spondyloarthritis: a cross-sectional study.

Objective: Despite biological drug therapy, pain remains a persistent complaint in patients with axial spondyloarthritis (axSpA). We aimed to investigate the effect of central sensitization (CS) on disease activity measures, quality of life, and clinical parameters in axSpA patients. Methods: We consecutively recruited axSpA patients who were followed up at our rheumatology outpatient clinic, and age- and sex-matched controls in this cross-sectional study. The central sensitization inventory, douleur neuropathique 4 (DN4) questions, and 2010 American College of Rheumatology fibromyalgia (FM) diagnostic criteria were applied to all individuals. The patients' clinical parameters were recorded. The data of the patient and control groups were compared. Results: Of the 116 axSpA patients (57 female) and 95 controls (46 female) who participated in this study, CS was determined in 46.6% of axSpA patients and 13.7% of controls (p<0.001). Patients with CS exhibited high disease activity, and poor quality of life and functionality than without it (all p<0.001). The median CS, frequency of FM and frequency of neuropathic pain were higher in patients than in the controls (all p<0.001). CS-related conditions, including anxiety and depression, were higher in axSpA patients than in controls (both p<0.05). Conclusion: The results showed that CS was common in axSpA patients, and patients with CS had higher disease activity, worse quality of life, and worse functional status than those without CS.

Is the C-reactive protein-to-albumin ratio the most remarkable simple inflammatory marker showing active disease in patients with axial spondyloarthritis, psoriatic arthritis, and rheumatoid arthritis?

OBJECTIVE: To learn which of the simple inflammation markers obtained from routine laboratory tests showed active disease best. METHODS: The study included 256 patients (102 patients with axial spondyloarthritis [axSpA], 54 with psoriatic arthritis [PsA], and 100 with rheumatoid arthritis [RA]). The results of the routine laboratory tests requested during the outpatient clinic visits of the patients were noted. Inflammation-related ratio/indices were then calculated from these laboratory tests. Active and inactive diseases were defined according to the disease activity scores for each disease. Logistic regression and receiver operating characteristic (ROC) analyses were performed to determine the best laboratory marker(s) showing active disease and its cutoff value for all three diseases. RESULTS: C-reactive protein to albumin ratio (CAR) was significantly higher in patients with active axSpA, PsA, and RA diseases than those with inactive diseases (p < 0.001, p = 0.006, and p < 0.001, respectively). In the logistic regression analysis, the CAR was the most important predictor of active disease in patients with axSpA, PsA, and RA. CAR had also showed the active disease at an acceptable level in axSpA and PsA and very well in RA. The cutoff values for active disease in axSpA, PsA, and RA were 0.75, 0.92, and 0.89, respectively. CONCLUSION: CAR may be a promising simple laboratory marker to distinguish active disease in patients with axSpA, PsA, and RA. Key Points • Acute phase reactants and circulating blood cells have become an important target because of the search for a disease activity marker that can be used cheaply and quickly in the daily outpatient routine. • One or more of these simple markers have been previously discussed in various studies with different hypotheses. • We aimed to determine which of the inflammation markers obtained from routine laboratory tests showed active disease and to determine a cutoff value for this/these marker(s). • CAR was the most important simple laboratory marker to distinguish active disease in patients with axSpA, PsA, and RA. In addition, CAR showed the active disease at an acceptable level in axSpA and PsA, and very well in RA.

Are follistatin-like protein 1 and follistatin-like protein 3 associated with inflammatory processes in patients with familial Mediterranean fever?

OBJECTIVE: Follistatin-like protein 1 (FSTL-1) and follistatin-like protein 3 (FSTL-3) are glycoproteins whose associations with inflammatory cytokines were reported in previous studies. However, it is not yet known whether they have an effect on the pathogenesis of familial Mediterranean fever (FMF). We aimed to detect the FSTL-1 and FSTL-3 levels and to determine their relationship to the attack status and mutation types in patients with FMF. METHODS: Fifty-six FMF patients and 22 healthy controls (HCs) were included in the study. Serum FSTL-1 and FSTL-3 levels were measured with the enzyme-linked immunosorbent assay method from collected serum samples. In addition, the MEditerranean FeVer (MEFV) gene mutation types of the patients were noted. RESULTS: Serum FSTL-1 levels were significantly higher in FMF patients than in HCs (p=0.005). However, there was no significant difference in FSTL-1 levels between patients in the attack period (n=26) and in the attack-free period (n=30). FSTL-3 levels were similar between FMF patients and HCs or patients in the attack period and in the attack-free period. Furthermore, the MEFV mutation type and attack status had no significant effect on FSTL-1 and FSTL-3 levels (p>0.05). CONCLUSION: Our results suggest that FSTL-1 may be associated with the pathogenesis of FMF, rather than FSTL-3. However, neither serum FSTL-1 nor FSTL-3 seems to be good markers to reflect inflammatory activity.

The influence of alexithymia on disease activity and quality of life in patients with axial spondyloarthritis: A cross-sectional study.

OBJECTIVE: To evaluate the prevalence of alexithymia and its influence on disease activity, quality of life, and clinical outcomes in axial spondyloarthritis (axSpA) patients. PATIENTS AND METHODS: This cross-sectional study included 110 (59 men and 51 women) consecutive axSpA patients who agreed to participate at our rheumatology outpatient clinic. Patient demographics, pain, disease activity measures, functionality, quality of life, alexithymia, psychological status, neuropathic pain, and fibromyalgia were evaluated. Patients were divided into 2 groups (without vs with alexithymia) and compared. The risk factors for alexithymia were evaluated. RESULTS: The prevalence of alexithymia in axSpA patients was 31.8% according to a Toronto Alexithymia Scale-20 cutoff of ≥61. The mean age and body mass index of patients were 41.25 ± 9.64 years and 27.73 ± 4.51 kg/m2 , respectively. Most patients with alexithymia were women. Patients with alexithymia had significantly high scores for depression, anxiety, fibromyalgia, disease activity, enthesitis, worse quality of life, and poor functionality (all P < 0.05). Female gender (odds ratio [OR] = 22.359), patient global assessment (OR = 7.873), Bath Ankylosing Spondylitis Functional Index (OR = 1.864), and fibromyalgia symptom severity (OR = 1.303) were found to be independent risk factors for alexithymia. CONCLUSION: The present study results showed that about one-third of axSpA patients had alexithymia, and the patients with alexithymia had higher disease activity, worse quality of life, and worse functional status than those without alexithymia. Female gender, patient global assessment, functional status, and fibromyalgia symptom severity were found to be important contributing factors to alexithymia.

Familial Mediterranean fever: Health-related quality of life and associated variables in a national cohort.

OBJECTIVES: This study aims to evaluate the effectivity of Familial Mediterranean Fever Quality of Life (FMF-QoL) Scale for the measurement of QoL in patients with FMF and to perform correlations between related clinical variables in Turkish patients. PATIENTS AND METHODS: This multicenter prospective study performed between December 2017 and November 2018 included 974 FMF patients (334 males, 640 females; median age: 35; range, 26 to 45 years). Sociodemographic characteristics and clinical features were recorded. All participants were asked to complete the FMF-QoL Scale, Short Form-36 (SF-36), Hospital Anxiety and Depression Scale (HADS), Health Assessment Questionnaire (HAQ), and Functional Assessment of Chronic Illness Therapy (FACIT) Scale. RESULTS: The median FMF-QoL Scale score was 26. Higher FMF-QoL Scale scores were shown to be related to female sex, illiteracy or primary education, monthly low-income (US$<300), smoking, late-onset FMF (>20 years), a higher number of attacks per month (>1/month), and severe disease. FMF-QoL Scale scores were correlated negatively with subscales of SF-36, and positively with HADS-anxiety and HADS-depression scores, HAQ and FACIT. CONCLUSION: Female sex, smoking, lower educational status, more severe disease, fatigue, and functional impairment were associated with poor QoL. FMF-QoL Scale was noted as a valid and simple patient-reported outcome instrument and correlated with the SF-36 scale.

Familial mediterranean fever: assessment of clinical manifestations, pregnancy, genetic mutational analyses, and disease severity in a national cohort.

The aims of this study were to investigate the main clinical and laboratory features, including pregnancy and genetic analysis, of Turkish Familial Mediterranean Fever (FMF) patients and to analyze the relationships between genotypic features, age of disease onset, clinical findings, and disease severity. A study was planned within a national network of 22 different centers. Demographics, clinical and laboratory findings, attack characteristics, drugs, pregnancy and birth history, disease severity, and gene mutation analyses were evaluated. Disease severity, assessed using a scoring system developed by Pras et al., was evaluated in relation to gene mutations and age of disease onset. A total of 979 patients (643 females and 336 males; mean age: 35.92 ± 11.97 years) with FMF were included in the study. Of a total of 585 pregnancies, 7% of them resulted in preterm birth and 18.1% resulted in abortions. During pregnancy, there was no FMF attack in 61.4% of patients. Of the MEditerranean FeVer (MEFV) mutations, 150 (24.3%) cases were homozygous, 292 (47.3%) cases were heterozygous, and 175 (28.4%) were compound heterozygous. Patients with homozygous gene mutations had more severe disease activity, earlier age of disease onset, higher rates of joint and skin involvement, sacroiliitis, and amyloidosis. Patients with compound heterozygous genotype displayed severe disease activity in close resemblance to patients with homozygous mutation. In addition, patients with compound heterozygous mutations had higher rates of protracted febrile myalgia and elevated fibrinogen levels. In 63.9% of compound heterozygous patients, age of onset was < 20 years, with greater disease severity, and high rates of attack frequency and colchicine resistance. Our results suggest that indicators for disease severity include early onset of disease and homozygous gene mutations. Furthermore, patients with compound heterozygous mutations displayed significant presentations of severe disease activity.