Pan American League of Associations for Rheumatology Recommendations for the Treatment of Psoriatic Arthritis.

OBJECTIVE: Psoriatic arthritis (PsA) is chronic disease that compromises multiple domains and might be associated with progressive joint damage, increased mortality, functional limitation, and considerably impaired quality of life. Our objective was to generate evidence-based recommendations on the management of PsA in Pan American League of Associations for Rheumatology (PANLAR) countries. METHODS: We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE)-ADOLOPMENT approach to adapt the 2019 recommendations of the European Alliance of Associations for Rheumatology. A working group consisting of rheumatologists from various countries in Latin America identified relevant topics for the treatment of PsA in the region. The methodology team updated the evidence and synthesized the information used to generate the final recommendations. These were then discussed and defined by a panel of 31 rheumatologists from 15 countries. RESULTS: Theses guidelines report 15 recommendations addressing therapeutic targets, use of antiinflammatory agents and corticosteroids, treatment with disease-modifying antirheumatic drugs (conventional synthetic, biologic, and targeted synthetic), therapeutic failure, optimization of biologic therapy, nonpharmacological interventions, assessment tools, and follow-up of patients with PsA. CONCLUSION: Here we present a set of recommendations to guide decision making in the treatment of PsA in Latin America, based on the best evidence available, considering resources, medical expertise, and the patient's values and preferences. The successful implementation of these recommendations should be based on clinical practice conditions, healthcare settings in each country, and a tailored evaluation of patients.

Cardiovascular Events, Malignancies, and Efficacy Outcomes in Latin American Patients With Rheumatoid Arthritis Receiving Tofacitinib or Tumor Necrosis Factor Inhibitors: A Post Hoc Analysis of the ORAL Surveillance Study.

BACKGROUND/OBJECTIVE: To assess safety/efficacy of tofacitinib and tumor necrosis factor inhibitors (TNFi) in patients from Latin America (LATAM) in ORAL Surveillance. METHODS: In ORAL Surveillance, 4362 patients with rheumatoid arthritis aged ≥50 years with ≥1 additional cardiovascular risk factor received tofacitinib 5 or 10 mg twice daily or TNFi. This post hoc analysis stratified patients by geographical location (LATAM, n = 1202; non-LATAM, n = 3160). Incidence rates (IRs; patients with first event/100 patient-years) and hazard ratios for adverse events of special interest were reported. Efficacy outcomes included Clinical Disease Activity Index and American College of Rheumatology 20/50/70 responses. RESULTS: Risk factors associated with cardiovascular disease and malignancies were less prevalent in the LATAM cohort compared with the non-LATAM cohort. IRs for patients receiving tofacitinib (combined doses) versus TNFi were 0.54 versus 0.28 (LATAM) and 1.14 versus 0.92 (non-LATAM) for major adverse cardiovascular events; 0.58 versus 0.27 (LATAM) and 1.33 versus 0.95 (non-LATAM) for malignancies excluding nonmelanoma skin cancer; and 0.69 versus 0.35 (LATAM) and 0.63 versus 0.33 (non-LATAM) for all-cause death. IRs for nonmelanoma skin cancer and venous thromboembolism were also numerically higher with tofacitinib versus TNFi and in the non-LATAM cohort versus LATAM. Efficacy was similar across treatment groups within each cohort. CONCLUSIONS: Adverse events of special interest were generally less frequent in LATAM versus non-LATAM patients, reflecting differences in baseline characteristics, and higher with tofacitinib versus TNFi in both cohorts, consistent with the overall findings of ORAL Surveillance. Our findings emphasize the importance of assessing individual risk factors to guide benefit/risk assessment and treatment decisions. CLINICAL TRIAL REGISTRATION NUMBER: NCT02092467.

Infections in patients with rheumatoid arthritis receiving tofacitinib versus tumour necrosis factor inhibitors: results from the open-label, randomised controlled ORAL Surveillance trial.

OBJECTIVES: To characterise infections in patients with rheumatoid arthritis (RA) in ORAL Surveillance. METHODS: In this open-label, randomised controlled trial, patients with RA aged≥50 years with ≥1 additional cardiovascular risk factor received tofacitinib 5 or 10 mg two times per day or a tumour necrosis factor inhibitor (TNFi). Incidence rates (IRs; patients with first events/100 patient-years) and hazard ratios (HRs) were calculated for infections, overall and by age (50-<65 years; ≥65 years). Probabilities of infections were obtained (Kaplan-Meier estimates). Cox modelling identified infection risk factors. RESULTS: IRs/HRs for all infections, serious infection events (SIEs) and non-serious infections (NSIs) were higher with tofacitinib (10>5 mg two times per day) versus TNFi. For SIEs, HR (95% CI) for tofacitinib 5 and 10 mg two times per day versus TNFi, respectively, were 1.17 (0.92 to 1.50) and 1.48 (1.17 to 1.87). Increased IRs/HRs for all infections and SIEs with tofacitinib 10 mg two times per day versus TNFi were more pronounced in patients aged≥65 vs 50-<65 years. SIE probability increased from month 18 and before month 6 with tofacitinib 5 and 10 mg two times per day versus TNFi, respectively. NSI probability increased before month 6 with both tofacitinib doses versus TNFi. Across treatments, the most predictive risk factors for SIEs were increasing age, baseline opioid use, history of chronic lung disease and time-dependent oral corticosteroid use, and, for NSIs, female sex, history of chronic lung disease/infections, past smoking and time-dependent Disease Activity Score in 28 joints, C-reactive protein. CONCLUSIONS: Infections were higher with tofacitinib versus TNFi. Findings may inform future treatment decisions. TRIAL REGISTRATION NUMBER: NCT02092467.

Disease activity and subcutaneous nodules are associated to severe periodontitis in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) was significantly associated with increased overall risk of periodontitis, both chronic, inflammatory pathologies leading to connective tissue breakdown and bone destruction. To identify clinical and/or serological variables routinely evaluated during follow-up of people with RA which are associated with the severity of their periodontal disease. An observational, cross-sectional study was carried out, which included RA patients according to ACR/EULAR 2010 criteria having chronic periodontal disease. RA clinical parameters (disease duration, erythrocyte sedimentation rate, serum C-reactive protein, disease activity (DAS28) and rheumatoid factor, presence of bone erosions and rheumatic nodules) and also corticosteroid therapy were considered. Periodontitis was evaluated according to the American Academy of Periodontology (1999) and chronic periodontitis was assessed by full mouth periapical radiographic examination, periodontal probing depth, clinical attachment level and bleeding index. A total of 110 subjects with RA and chronic periodontitis were included. The female/male relation was 5.1, and no significant differences between genres were found in rheumatic or oral variables. RA patients with longer disease duration, higher disease activity and with rheumatic nodules had significantly greater periodontitis severity. Multivariate analysis confirmed that severe periodontitis was associated with DAS283 4.1 (OR 51.4, CI 95% 9.4-281.5) and the presence of rheumatic nodules (OR 6.4, CI 95% 1.3-31.6). Disease activity and rheumatic nodules were strongly associated with severe periodontitis. Based on these findings it would be desirable to include interdisciplinary management at an early stage of RA to ensure comprehensive treatment of both pathologies.

Efficacy, Safety, and Immunogenicity of Biosimilar Etanercept (Enerceptan) Versus Its Original Form in Combination With Methotrexate in Patients With Rheumatoid Arthritis: A Randomized, Multicenter, Evaluator-Blinded, Noninferiority Study.

BACKGROUND: Enerceptan (EtaBS) has been developed as a proposed biosimilar of etanercept. METHODS: This randomized, multicenter, evaluator-blinded, noninferiority study conducted in Argentina included adults with active, moderate, and severe rheumatoid arthritis with inadequate response to methotrexate. Subjects were randomly assigned to 32 weeks treatment with EtaBS (n = 99) or etanercept (n = 51) at a weekly 50-mg dose administered subcutaneously. Patients were categorized according to prior use of biologic disease-modifying antirheumatic drugs and concomitant use of steroids. The primary efficacy endpoint was ACR20 response rate at week 32. Safety, immunogenicity, and steady-state concentration of both drugs were evaluated. The noninferiority margin for ACR20 was estimated at 12%. RESULTS: In the per-protocol population, 85 subjects (92.4%) treated with EtaBS and 44 subjects (93.6%) treated with etanercept achieved ACR20 (difference, -1.2%; 95% confidence interval, -10.1% to 7.6%). Frequent adverse drug reactions occurred in 34.3% and 38% of subjects treated with EtaBS and etanercept, respectively. The most common reaction was upper respiratory tract infection. Six and 3 serious adverse events occurred in 4 and 3 subjects treated with EtaBS and etanercept, respectively. Injection site reactions occurred in 67.7% and 66.0% of subjects treated with EtaBS and etanercept, respectively. Two subjects treated with EtaBS and 1 subject treated with etanercept developed antibodies by week 32. CONCLUSIONS: Efficacy outcomes for EtaBS were noninferior to original etanercept in patients with moderate-to-severe rheumatoid arthritis with inadequate response to methotrexate. Safety and immunogenicity results were comparable between the two. This study is a major step toward improving access to biologics in Latin America.

Incidence Rates of Interstitial Lung Disease Events in Tofacitinib-Treated Rheumatoid Arthritis Patients: Post Hoc Analysis From 21 Clinical Trials.

BACKGROUND/OBJECTIVE: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Interstitial lung disease (ILD) is an extra-articular manifestation of RA. We investigated incidence rates of ILD in patients with RA, receiving tofacitinib 5 or 10 mg twice daily, and identified potential risk factors for ILD. METHODS: This post hoc analysis comprised a pooled analysis of patients receiving tofacitinib 5 or 10 mg twice daily or placebo from 2 phase (P)1, 10 P2, 6 P3, 1 P3b/4, and 2 long-term extension studies. Interstitial lung disease events were adjudicated as "probable" (supportive clinical evidence) or "possible" (no supportive clinical evidence) compatible adverse events. Incidence rates (patients with events per 100 patient-years) were calculated for ILD events. RESULTS: Of 7061 patients (patient-years of exposure = 23,393.7), 42 (0.6%) had an ILD event; median time to ILD event was 1144 days. Incidence rates for ILD with both tofacitinib doses were 0.18 per 100 patient-years. Incidence rates generally remained stable over time. There were 17 of 42 serious adverse events (40.5%) of ILD; for all ILD events (serious and nonserious), 35 of 42 events (83.3%) were mild to moderate in severity. A multivariable Cox regression analysis identified age 65 years or older (hazard ratio 2.43 [95% confidence interval, 1.13-5.21]), current smokers (2.89 [1.33-6.26]), and Disease Activity Score in 28 joints-erythrocyte sedimentation rate score (1.30 [1.04-1.61]) as significant risk factors for ILD events. CONCLUSIONS: Across P1/2/3/4/long-term extension studies, incidence rates for ILD events were 0.18 following tofacitinib treatment, and ILD events were associated with known risk factors for ILD in RA.

Depression Is a Major Determinant of Functional Capacity in Rheumatoid Arthritis.

OBJECTIVE: The aim of this study was to determine the prevalence of depression among rheumatoid arthritis (RA) Argentinean patients and its association with sociodemographic and clinical factors. METHODS: We performed a cross-sectional study of consecutive adults with RA. Sociodemographic data, comorbidities, RA disease activity, and current treatment were assessed. The following instruments were used to evaluate quality of life (EQ-5D-3 L [EURO Quality 5-dimension 3 lines], QOL-RA [Quality of Life-Rheumatoid Arthritis]), functional capacity (HAQ-A [Health Assessment Questionnaire-Argentinean version]), and depression (PHQ-9 [Patient Health Questionnaire 9]; scores 5-9: mild, 10-14: moderate, 15-19: moderate-severe, and ≥20: severe depression, a cutoff value ≥10 is diagnostic of major depression). RESULTS: Two hundred fifty-eight patients were included, with a median disease duration of 9 years (interquartile range, 3.6-16.7 years). The m PHQ-9 score was 6 (interquartile range, 2-12.3 years). The prevalence of major depression was 33.8%. The frequency of mild, moderate, moderate/severe, and severe depression was 66 (25.6%), 42 (16.3%), 27 (10.5%), and 18 (7%), respectively. Patients with major depression had worse functional capacity (HAQ-A: mean ± SD, 1.6 ± 0.8 vs. 0.7 ± 0.7; p < 0.0001), poorer quality of life (QOL-RA: mean ± SD, 5.4 ± 1.8 vs. 7.3 ± 1.6; p < 0.0001), greater pain (visual analog scale: mean ± SD, 56.2 ± 27.5 mm vs. 33.4 ± 25.7 mm; p < 0.0001), higher disease activity (Disease Activity Score in 28 joints: mean ± SD, 4.3 ± 1.4 vs. 3.3 ± 1.3; p < 0.0001), higher frequency of comorbidities (67% vs. 33%; p = 0.017), and lower frequency of physical activity (22% vs. 35%; p = 0.032). In the multivariate analysis, patients with moderate and severe depression had worse functional capacity (odds ratio, 2.1; 95% confidence interval, 1.6-4.3; p < 0.0001) and quality of life (odds ratio, 0.7; 95% confidence interval, 0.5-0.8; p < 0.0001), independently of disease activity. CONCLUSIONS: A third of RA patients in this Argentinean cohort had major depression. In those patients, depression was associated with worst functional capacity and quality of life.

Validation and cultural adaptation of the qualisex questionnaire in patients with axial spondyloarthritis in Argentina.

The Qualisex questionnaire was developed and validated to assess sexuality in patients with rheumatoid arthritis. To the best of our knowledge, there is no instrument to evaluate sexuality in axial spondyloarthritis (axSpA). For this reason, the objective of this study was to validate and adapt the Qualisex questionnaire in axSpA and evaluate the impact of the disease on patients' sexuality. Cross sectional study. Consecutive patients, with ≥ 21 years of age, diagnosed with axSpA according to ASAS'09 criteria were included. Sexual health was assessed using the Qualisex questionnaire. The original version was translated to Spanish and adapted to axSpA. Internal consistency, and test re-test reliability was calculated. Criterion and construct validity were assessed by comparing the Qualisex with parameters of disease activity functional capacity and quality of life. 61 patients were invited to participate in the study, 11 of whom refused. 50 patients were included; 40 (80%) were males, with a median age of 47 years (IQR 21-72) and a median disease duration of 13 years (IQR 1-46). Reproducibility was excellent with an ICC of 0.99 (95% CI 0.65-1). The Qualisex had a good correlation with different disease evaluation parameters. The Qualisex was significantly higher among women (5.4 in women vs. 2.5 in men, p = 0.02), unemployed (4.7 in unemployed vs. 2.3 in employed, p = 0.01), in patients with higher disease activity (4.2 in active patients vs. 1.6 in inactive patients, p = 0.01), and it was lower in patients receiving biologic therapy (BT) (1.9 with BT vs. 3.8 without BT, p = 0.01). Multivariable analysis showed that female sex, longer disease duration and higher disease activity were independently associated with a greater impact on sexuality. The Qualisex adapted to axSpA is a valid and reliable questionnaire. Female axSpA patients, those with longer disease duration and higher disease activity presented a worse sexual life.

Safety of Tofacitinib in the Treatment of Rheumatoid Arthritis in Latin America Compared With the Rest of the World Population.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic, autoimmune disease characterized by joint destruction. Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. This post hoc analysis assessed the safety of tofacitinib in Latin American (LA) patients with RA versus the Rest of World (RoW) population. METHODS: Data were pooled from 14 clinical studies of tofacitinib: six Phase 2, six Phase 3 and two long-term extension studies. Incidence rates (IRs; patients with events/100 patient-years of treatment exposure) were calculated for safety events of special interest combined across tofacitinib doses. 95% confidence intervals (CI) for IRs were calculated using the maximum likelihood method. Descriptive comparisons were made between LA and RoW (excluding LA) populations. RESULTS: This analysis included data from 984 LA patients and 4687 RoW patients. IRs for safety events of special interest were generally similar between LA and RoW populations, with overlapping 95% CIs. IRs for discontinuation due to adverse events, serious infections, tuberculosis, all herpes zoster (HZ), serious HZ, malignancies (excluding non-melanoma skin cancer) and major adverse cardiovascular events were numerically lower for LA versus RoW patients; IR for mortality was numerically higher. No lymphoma was reported in the LA population versus eight cases in the RoW population. Exposure (extent and length) was lower in the LA population (2148.33 patient-years [mean = 2.18 years]) versus RoW (10515.68 patient-years [mean = 2.24 years]). CONCLUSION: This analysis of pooled data from clinical studies of tofacitinib in patients with RA demonstrates that tofacitinib has a consistent safety profile across LA and RoW patient populations.

Clinical and MRI responses to etanercept in early non-radiographic axial spondyloarthritis: 48-week results from the EMBARK study.

OBJECTIVE: To evaluate the efficacy and safety of etanercept (ETN) after 48 weeks in patients with early active non-radiographic axial spondyloarthritis (nr-axSpA). METHODS: Patients meeting Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axSpA, but not modified New York radiographic criteria, received double-blind ETN 50 mg/week or placebo (PBO) for 12 weeks, then open-label ETN (ETN/ETN or PBO/ETN). Clinical, health, productivity, MRI and safety outcomes were assessed and the 48-week data are presented here. RESULTS: 208/225 patients (92%) entered the open-label phase at week 12 (ETN, n=102; PBO, n=106). The percentage of patients achieving ASAS40 increased from 33% to 52% between weeks 12 and 48 for ETN/ETN and from 15% to 53% for PBO/ETN (within-group p value <0.001 for both). For ETN/ETN and PBO/ETN, the EuroQol 5 Dimensions utility score improved by 0.14 and 0.08, respectively, between baseline and week 12 and by 0.23 and 0.22 between baseline and week 48. Between weeks 12 and 48, MRI Spondyloarthritis Research Consortium of Canada sacroiliac joint (SIJ) scores decreased by -1.1 for ETN/ETN and by -3.0 for PBO/ETN, p<0.001 for both. Decreases in MRI SIJ inflammation and C-reactive protein correlated with several clinical outcomes at weeks 12 and 48. CONCLUSIONS: Patients with early active nr-axSpA demonstrated improvement from week 12 in clinical, health, productivity and MRI outcomes that was sustained to 48 weeks. TRIAL REGISTRATION NUMBER: NCT01258738.

Effects of cigarette smoking on early arthritis: a cross-sectional study-data from the Argentine Consortium for Early Arthritis (CONAART).

Our objective was to analyze the effects of cigarette smoking on disease activity, functional capacity, radiographic damage, serology and presence of extraarticular manifestations in patients with rheumatoid arthritis and undifferentiated arthritis. This is a cross-sectional study of 1,305 patients (729 with rheumatoid arthritis and 576 with undifferentiated arthritis) from CONAART, the Argentine Consortium for Early Arthritis that includes patients older than 16 years with <2 years of disease. Sociodemographic data, clinical characteristics of the disease and smoking history were collected. In patients with rheumatoid arthritis the disease activity score of 28 joints was 5.4 ± 1.3 in current smokers, 5.2 ± 1.4 in former smokers and 5.1 ± 1.4 in never smokers (p = 0.011). The simple erosion narrowing score was higher in current smokers and former smokers than in never smokers (M 14.0, R Q 6.0-21.0; M 15.0, R Q 7.0-24.0; M 10.0, R Q 5.0-17.0; p = 0.006). Current smokers had higher rheumatoid factor titer (M 160.0, R Q 80.0-341.0) than former smokers (M 146.8, R Q 6.03-255.5) and never smokers (M 15.0, R Q 9.0-80.0) (p = 0.004). The variable independently associated with tobacco exposure was simple erosion narrowing score (OR = 1.03, 95 % CI 1.00-1.05; p = 0.012). In patients with undifferentiated arthritis, an association between smoking status and parameters of activity or radiographic damage was not observed. Neither was tobacco exposure related to the presence of extraarticular manifestations or to the degree of disability in any of the two groups of patients. No relation was found between disease activity and severity, and number of packs smoked per year. Tobacco.

Work instability in rheumatoid arthritis patients from Argentina: prevalence and associated factors.

To determine the prevalence of and associated factors to work instability (WI) in rheumatoid arthritis (RA) Argentinean patients. Observational cross-sectional study that assessing employment status in currently working RA patients. They answered the validated version of RA work instability scale (RA-WIS). High-risk WI was considered when RA-WIS was ≥17. Factors associated with high-risk WI were examined by univariable and multivariable analysis. Four-hundred and fifty RA patients were enrolled; of these, 205 patients were currently employed, but only 172 have completed questionnaires required [RA-WIS and health assessment questionnaire (HAQ-A)]. Their mean age was 49.3 ± 10.8 years; 81.3 % were female; and their mean disease duration was 8.1 ± 7.2 years. Fifty-two percent of patients were doing manual work. The mean RA-WIS score was 11.4 ± 6.8, and 41 % of patients had a high-risk WI. High-risk WI was associated with radiographic erosions (p < 0.001) and HAQ-A >0.87 (p < 0.001) in the univariable analysis, whereas in the multivariable logistic regression analysis the variables associated with a high-risk WI were as follows: HAQ-A >0.87 [odds ratio (OR) 12.31; 95 % CI 5.38-28.18] and the presence of radiographic erosions (OR 4.848; 95 % CI 2.22-10.5). In this model, having a higher monthly income (OR 0.301; 95 % CI 0.096-0.943) and a better functional class (OR 0.151; 95 % CI 0.036-0.632) were protective. Forty-one percent of RA working patients had high-risk WI. The predictors of high RA-WIS were HAQ-A ≥0.87 and radiographic erosions, whereas having a better functional class and have higher incomes were protective.

Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: two-year efficacy and safety findings from AMPLE trial.

OBJECTIVES: To compare over 2 years the safety, efficacy and radiographic outcomes of subcutaneous abatacept versus adalimumab, in combination with methotrexate (MTX), in patients with rheumatoid arthritis (RA). METHODS: AMPLE is a phase IIIb, 2-year, randomised, investigator-blinded study with a 1-year primary endpoint. Biologic-naive patients with active RA and an inadequate response to MTX were randomised to 125 mg abatacept weekly or 40 mg adalimumab bi-weekly, both with a stable dose of MTX. RESULTS: Of 646 patients randomised, 79.2% abatacept and 74.7% adalimumab patients completed year 2. At year 2, efficacy outcomes, including radiographic, remained comparable between groups and with year 1 results. The American College Rheumatology 20, 50 and 70 responses at year 2 were 59.7%, 44.7% and 31.1% for abatacept and 60.1%, 46.6% and 29.3% for adalimumab. There were similar rates of adverse events (AEs) and serious adverse events (SAEs). More serious infections occurred with adalimumab (3.8% vs 5.8%) including two cases of tuberculosis with adalimumab. There were fewer discontinuations due to AEs (3.8% vs 9.5%), SAEs (1.6% vs 4.9%) and serious infections (0/12 vs 9/19 patients) in the abatacept group. Injection site reactions (ISRs) occurred less frequently with abatacept (4.1% vs 10.4%). CONCLUSIONS: Through 2 years of blinded treatment in this first head-to-head study between biologic disease-modifying antirheumatic drugs in RA patients with an inadequate response to MTX, subcutaneous abatacept and adalimumab were similarly efficacious based on clinical, functional and radiographic outcomes. Overall, AE frequency was similar in both groups but there were less discontinuations due to AEs, SAEs, serious infections and fewer local ISRs with abatacept.

Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: findings of a phase IIIb, multinational, prospective, randomized study.

OBJECTIVE: There is a need for comparative studies to provide evidence-based treatment guidance for biologic agents in rheumatoid arthritis (RA). Therefore, this study was undertaken as the first head-to-head comparison of subcutaneous (SC) abatacept and SC adalimumab, both administered along with background methotrexate (MTX), for the treatment of RA. METHODS: Patients with active RA who were naive to treatment with biologic agents and had an inadequate response to MTX were randomly assigned to receive 125 mg SC abatacept weekly or 40 mg SC adalimumab biweekly, both given in combination with MTX, in a 2-year study. The primary end point was treatment noninferiority, assessed according to the American College of Rheumatology 20% improvement response (ACR20) at 1 year. RESULTS: Of the 646 patients who were randomized and treated, 86.2% receiving SC abatacept and 82% receiving SC adalimumab completed 12 months of treatment. At 1 year, 64.8% of patients in the SC abatacept group and 63.4% in the SC adalimumab group demonstrated an ACR20 response; the estimated difference between groups was 1.8% (95% confidence interval -5.6%, 9.2%), thus demonstrating the noninferiority of abatacept compared to adalimumab. All efficacy measures showed similar results and kinetics of response between treatments. The rate of radiographic nonprogression (defined as a total modified Sharp/van der Heijde score [SHS] less than or equal to the smallest detectable change) was 84.8% for SC abatacept-treated patients and 88.6% for SC adalimumab-treated patients, while the mean change from baseline in the total SHS was 0.58 and 0.38, respectively. In the SC abatacept and SC adalimumab groups, the incidence of serious adverse events (SAEs) was 10.1% and 9.1%, respectively, and the rate of serious infections was 2.2% and 2.7%, respectively. In patients treated with SC abatacept, the frequency of discontinuations due to AEs was 3.5% and discontinuations due to SAEs was 1.3%, while in patients treated with SC adalimumab, the frequencies were 6.1% and 3%, respectively. Injection site reactions occurred in 3.8% of patients receiving SC abatacept compared to 9.1% of patients receiving SC adalimumab (P=0.006). CONCLUSION: The results demonstrate that SC abatacept and SC adalimumab have comparable efficacy in patients with RA, as shown by similar kinetics of response and comparable inhibition of radiographic progression over 1 year of treatment. The safety was generally similar, other than the occurrence of significantly more local injection site reactions in patients treated with SC adalimumab.

Rheumatoid arthritis in Latin Americans enriched for Amerindian ancestry is associated with loci in chromosomes 1, 12, and 13, and the HLA class II region.

OBJECTIVE: To identify susceptibility loci for rheumatoid arthritis (RA) in Latin American individuals with admixed European and Amerindian genetic ancestry. METHODS: Genotyping was performed in 1,475 patients with RA and 1,213 control subjects, using a customized BeadArray containing 196,524 markers covering loci previously associated with various autoimmune diseases. Principal components analysis (EigenSoft package) and Structure software were used to identify outliers and define the population substructure. REAP software was used to define cryptic relatedness and duplicates, and genetic association analyses were conducted using Plink statistical software. RESULTS: A strong genetic association between RA and the major histocompatibility complex region was observed, localized within BTNL2/DRA-DQB1- DQA2 (P = 7.6 × 10(-10) ), with 3 independent effects. We identified an association in the PLCH2-HES5-TNFRSF14-MMEL1 region of chromosome 1 (P = 9.77 × 10(-6) ), which was previously reported in Europeans, Asians, and Native Canadians. We identified one novel putative association in ENOX1 on chromosome 13 (P = 3.24 × 10(-7) ). Previously reported associations were observed in the current study, including PTPN22, SPRED2, STAT4, IRF5, CCL21, and IL2RA, although the significance was relatively moderate. Adjustment for Amerindian ancestry improved the association of a novel locus in chromosome 12 at C12orf30 (NAA25) (P = 3.9 × 10(-6) ). Associations with the HLA region, SPRED2, and PTPN22 improved in individuals positive for anti-cyclic citrullinated peptide antibodies. CONCLUSION: Our data define, for the first time, the contribution of Amerindian ancestry to the genetic architecture of RA in an admixed Latin American population by confirming the role of the HLA region and supporting the association with a locus in chromosome 1. In addition, we provide data for novel putative loci in chromosomes 12 and 13.

Construct validity and responsiveness of the simplified version of Ankylosing Spondylitis Disease Activity Score (SASDAS) for the evaluation of disease activity in axial spondyloarthritis.

BACKGROUND: Over the last decade, significant progresses have been achieved in the development and validation of new tools for the evaluation of disease activity in axial spondyloarthritis (SpA). Despite they play a key role in the assessment of these patients, the calculation scores are relatively complex and difficult to be quickly assessed in the busy daily clinical practice. OBJECTIVES: To test the construct validity of the Simplified Ankylosing Spondylitis Disease Activity Score (SADSAS) to define disease activity and compare its internal and external responsiveness with the Ankylosing Spondylitis Disease Activity Score (ASDAS) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in patients with axial SpA. METHODS: The patient cohort comprised 397 consecutive axial SpA patients who had never been treated with tumor necrosis factor (TNF) blockers. Clinical and laboratory outcome assessments were performed at baseline, and at week 24. The following parameters were evaluated: BASDAI, ASDAS-CRP, ASDAS-ESR, and SASDAS. Construct convergent validity was evaluated by correlating SASDAS with ASDAS CRP/ESR, BASDAI, Bath Ankylosing Spondylitis Functional Index (BASFI) and EuroQol five-dimensional (EQ-5D) questionnaire. One hundred and fifty-six patients were observed longitudinally for 6 months. Responsiveness was assessed after six months of treatment with sulfasalazine (SSZ) or biologics. Internal responsiveness was evaluated by using the effect size (ES) and standardized response mean (SRM). External responsiveness was investigated by receiver operating characteristic (ROC) analysis. Change scores were compared by calculating paired t-test statistic for the difference. RESULTS: In testing for convergent validity a strong correlations (p < 0.0001) were observed between both SASDAS and ASDAS-ESR (r = 0.835), and ASDAS-CRP (r = 0.805). Strong correlations (p < 0.0001) were also found between SASDAS and BASDAI score (r = -0.886), SASDAS and BASFI scores (rho = 0.588) and SASDAS and EQ-5D scores (rho = -0.579). The cross-classification showed a significant overall agreement (defined as the percentage of observed exact agreements) for SASDAS vs ASDAS-ESR (weighted k = 0.704) and for SASDAS vs ASDAS-CRP (k = 0.661). The most efficient composite measure in detecting change was the ASDAS-CRP (ES 1.95 and SRM 0.97). The responsiveness of SASDAS was slightly higher to ASDAS-ESR with an ES of 1.62 and 1.33, and an SRM of 0.88 and 0.71, respectively. The BASDAI appear to be the less responsive (ES = 0.93 and SRM = 0.52). The area under ROC curve of the SASDAS gives similar results to those provided by ASDAS CRP/ESR. The score changes of all combinations were highly correlated (p < 0.0001). CONCLUSIONS: The new SASDAS is a highly effective measure in assessing disease activity and it showed comparable internal and external responsiveness with respect to the ASDAS ESR/CRP response criteria in patients with axial SpA. SASDAS is easy to calculate and, therefore, appear suitable for clinical decision making, epidemiologic research, and clinical trials.

Hyposalivation and periodontal disease as oral non-articular characteristics in rheumatoid arthritis.

OBJECTIVE: To investigate the association among rheumatoid arthritis (RA), saliva production, and periodontal status. METHODS: An observational study was carried out on 103 subjects with RA and 103 without RA matched by sex and age. Rheumatologic evaluation included serological and clinical variables. A full mouth periodontal examination was performed according to the American Academy of Periodontology (1999). Resting and stimulated whole salivary flows were determined after spiting during 5 min. RESULTS: RA was associated with a higher prevalence of severe periodontitis (12% vs. 4%), with a marked reduction in resting and stimulated saliva production, and with a higher prevalence of resting (19% vs. 0%) and also stimulated hyposalivation (54% vs. 10%), compared with the control group. The differences in mean resting and stimulated salivary flows between RA and control groups persisted after the exclusion of people with hyposalivation. Saliva production was not associated with the presence or the severity of periodontal disease, or with the rheumatic clinical characteristics of the patients. CONCLUSIONS: More than 50% of people with RA have some degree of reduction in their salivary flows, an affection not associated with the periodontal status or rheumatic activity, which are the expression of the two related inflammatory diseases. The influence of autonomic dysfunction on hyposalivation can be considered. While periodontitis would be a disease-associated comorbidity of RA, poor saliva production should be included among the extra-articular manifestations. Key Points • Rheumatoid arthritis patients are more prone to suffer from periodontitis and/or hyposalivation. • Periodontal disease is more prevalent in people with rheumatoid arthritis and also an association was found between the severities of both pathologies. • More than 50% of people with RA would have some degree of reduction in their salivary flows, an affection not associated with the periodontal status or rheumatic activity. • Reduced saliva production in rheumatoid arthritis patients should be included among the extra-articular manifestations.