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Objective: To determine the dynamics of serum levels of TNF-α in patients with juvenile idiopathic arthritis (JIA) treated with anti-TNF-α biological drugs and investigate their association with the disease activity. Methods: We conducted a single-centre, observational cohort study in 98 patients with JIA (30 boys, 68 girls, mean age 11.3 years) treated with anti-TNF-α biological drugs. Clinical examinations and laboratory assessments of serum levels of TNF-α were performed before starting therapy with biological drug and at 6-month intervals afterwards up to 2.5 years. Results: The analysis of serum levels of TNF-α in relation to the disease activity states showed the highest mean serum levels of TNF-α in patients on etanercept who had low disease activity states and in patients on adalimumab who had inactive disease. The correlation analysis in patients with JIA treated with etanercept or adalimumab showed a weak negative correlation between the serum levels of TNF-α and JADAS10 scores (p = 0.007), (r = − 0.177). Conclusion: The assessment of serum levels of TNF-α in children with JIA during treatment with etanercept or adalimumab is not a reliable biomarker of disease activity or immunological remission. Longitudinal measurement of TNF-α has no added clinical value in patients with JIA treated with anti-TNF-α biological drugs. Key Points • There is limited evidence regarding the effect of anti-TNF therapy on serum concentrations of TNF-α in patients with juvenile idiopathic arthritis • Our study showed an increase in the serum level of TNF-α after the initiation of therapy with either etanercept or adalimumab, which was more significant in patients with inactive or low disease activity • Serum TNF-α is most likely not biologically active during therapy with TNF-α inhibitors and therefore not a reliable biomarker of disease activity or immunological remission in patients with juvenile idiopathic arthritis [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to examine pre-treatment and post-treatment hemogram-derived inflammatory biomarkers in patients with rheumatoid arthritis (RA) who received anti-tumor necrosis factor (TNF)-α treatment. Material and methods: The data of 1182 patients with RA were screened. Among them, 207 patients who met the eligibility criteria were included in the retrospective study. Demographic parameters, disease activity, and blood cell-derived indexes were evaluated. The neutrophil–lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and hemoglobin-red cell distribution width (Hb/RDW) rates were evaluated before treatment and at the third month of treatment in patients with RA who received anti-TNF-α treatment. Results: According to the EULAR response criteria, 12.6% of the 207 patients responded to anti-TNF-α treatment as none, 21.3% as good, and 66.2% as moderate, respectively. Post-treatment NLR and PLR values were significantly lower than pre-treatment values (p < 0.001), whereas post-treatment LMR and Hb/RDW values were significantly higher than pre-treatment values (respectively, p = 0.001 and p = 0.012). The difference between pre-treatment and post-treatment values of LMR and Hb/RDW was significantly higher when compared to the moderate + good response groups than the none-response group (p = 0.002 and p = 0.014, respectively). However, in the receiver operating characteristic curve analysis, these parameters were not found to be significant in predicting treatment response. Conclusion: Significant changes were detected in hemogram-derived inflammatory markers of the groups responding to anti-TNF-α treatment. They can be used as a guide during treatment follow-up. Yet, they do not predict treatment response. Key Points • RA may manifest with periods of remission and activation, and regular follow-up is essential. • There is a demand for readily available, reproducible, and cost-effective parameters to assess treatment response. • Hemogram-derived inflammatory markers differ in relation to anti-TNF-α treatment response in RA. • None of those markers demonstrate an acceptable predictive performance in distinguishing patients based on their response to TNF-α inhibitors. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the efficacy and safety of Janus kinase (JAK) inhibitors (Jakinibs) in the treatment of psoriasis and psoriatic arthritis (PsA). Methods: Databases including PubMed, Embase, Web of Science, and Cochrane Library were searched for randomized controlled trials on the efficacy and safety of Jakinibs in treating psoriasis and PsA from inception to July 2021. A systematic review and meta-analysis were performed to estimate pooled relative risk (RR) and 95% confidence interval (CI). Results: Seventeen clinical trials (16 publications) comprising 6802 patients were included. All Jakinibs demonstrated significantly higher response rates compared with placebo (ACR20: RR 2.09, 95% CI 1.90–2.30; PASI75: RR 4.03, 95% CI 3.13–5.18). Within the subgroup analysis, the response rates defined by ACR20 were highest for filgotinib (RR 2.40, 95% CI 1.67–3.45), followed by upadacitinib, tofacitinib, and deucravacitinib. The proportion of patients achieving PASI75 response in the tofacitinib 10 mg twice daily group was significantly higher than that in the tofacitinib 5 mg group. Regarding safety, the incidence of adverse events (AEs) was significantly higher for Jakinibs compared with placebo (RR 1.17, 95% CI 1.11–1.23). Of note, a considerable increase in the risk of infections including upper respiratory tract and herpes zoster infection was observed among patients in the treatment group. For tofacitinib, upadacitinib, and filgotiniband, infection was the most prevalent AE. Moreover, AEs in the 10 mg tofacitinib group were higher than those in the 5 mg tofacitinib group. Conclusion: Jakinibs are efficacious interventions for the treatment of psoriasis and PsA, but they are associated with an increased risk of AEs when compared with placebo. The long-term efficacy and safety data require further evaluation. Key Points • This systematic review investigated and compared the efficacy and safety of different Jakinibs including the novel selective TYK2 inhibitors. • Jakinibs are efficacious interventions for the treatment of psoriasis and PsA. • A relatively higher dosing schedule of Jakinibs is associated with increased toxicity. [ABSTRACT FROM AUTHOR]

Objective: To assess the clinical equivalence of TQ-Z2301, a biosimilar of adalimumab, to the reference adalimumab in the treatment of Chinese patients with active ankylosing spondylitis. Methods: This multicenter, randomized, double-blind, positive-controlled phase III clinical trial was conducted in 19 centers across China. Chinese adults with active ankylosing spondylitis despite being treated with non-steroidal anti-inflammatory drugs for ≥ 4 weeks were randomized in a 1:1 ratio to subcutaneously receive 40 mg of TQ-Z2301 or adalimumab every other week for 24 weeks. The primary endpoint was the percentage of patients who achieved at least 20% improvement according to the Assessment of Spondyloarthritis International Society criteria (ASAS20) at week 24. The equivalence was established if the 90% CI for RR of ASAS20 between two groups at week 24 fell within (0.80, 1.25). Secondary endpoints included efficacy measures of disease activity, spinal mobility, physical function and quality of life, immunogenicity, and pharmacokinetic parameters. Safety analysis was done for all patients who received at least one study drug. Results: A total of 380 patients were enrolled in the study between September 2018 and October 2019, including 188 in the TQ-Z2301 group and 192 in the adalimumab group. In the full analysis population, the ASAS20 response rate at week 24 was 86.70% in the TQ-Z2301 group, and 80.73% in the adalimumab group, the RR of ASAS20 for TQ-Z2301 versus adalimumab was 1.074, 90% CI (0.997, 1.157), fell within the predefined equivalence boundary (0.80, 1.25). Except for the SF-36 at week 12, there was no statistical difference between the two groups for all the secondary endpoints (P>0.05). The incidence of adverse events group was 82.45% in the TQ-Z2301, and 83.85% in the adalimumab group, the safety profile of the two groups was similar. The profiles of immunogenicity and pharmacokinetics were also similar between the two groups. Conclusion: TQ-Z2301 is equivalent to adalimumab for the treatment of Chinese patients with active ankylosing spondylitis. The safety, immunogenicity, and pharmacokinetic characteristics of both drugs are similar. Trial registration: The study (CTR20181863) was registered in the Chinese Clinical Trial Registry on 19 October 2018. Key Points • TQ-Z2301 showed the equivalence of efficacy compared with the reference adalimumab for the treatment of Chinese patients with active ankylosing spondylitis. • The safety, immunogenicity, and pharmacokinetics profiles of TQZ-2301 were similar to those of the reference adalimumab. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the 12-month efficacy and safety profile of adalimumab and etanercept in patients with ankylosing spondylitis (AS) and total spinal ankylosis (TSA). Type of study design: Case-series follow-up study. Design: Twenty-eight patients (26 men and 2 women) with active AS (BASDAI > 4) and TSA were treated as follows: 19 patients receiving adalimumab and 9 patients receiving etanercept. Twelve-month data related to the efficacy and safety of these two TNF-alpha inhibitors were evaluated. The primary endpoint was ASAS 20 (the ASsessment in AS International Working Group criteria for 20% improvement) at weeks 12 and 52. Other measures that were evaluated were function (BASFI), disease activity (BASDAI), patient's and physician's global disease assessment on visual analogue scale (VAS) and C-reactive protein. Results: In both adalimumab and etanercept groups, there was a significant improvement in all observed variables (baseline compared to weeks 12 and 52). This improvement was sustained for the whole follow-up period. In the adalimumab group, at week 12, ASAS 20 was achieved in 18/19 patients and at week 52 in 17/19 patients. In the etanercept group, at week 12 ASAS 20 was achieved in all patients and at week 52 in 6/9 patients. Conclusion: In patients with active AS and TSA, adalimumab and etanercept treatment showed significant improvement in function and disease activity. No serious side effects or adverse effects were observed in our cohort. Key Points • TNF-alpha inhibitors can be effective treatment options for patients with AS and having total spinal ankylosis. • Patients with advanced AS should not be disregarded as good candidates for treatment with biologic disease-modifying antirheumatic drugs. [ABSTRACT FROM AUTHOR]

Objective: The equivalence of the biosimilar HS016 to adalimumab (Humira) for the treatment of active ankylosing spondylitis (AS) patients has been previously validated. The aim was to compare the efficacy of HS016 and adalimumab in stratified subgroups at different time points using Health Assessment Questionnaire for Spondyloarthropathies (HAQ-S) and short form 36 (SF-36) questionnaires. Methods: We carried out a multicenter, randomized, double-blind, parallel, positive control, phase 3 trial of patients with active AS. They were selected randomly to be subcutaneously administered 40 mg HS016 or adalimumab every 2 weeks for a total treatment period of 24 weeks in a 2:1 ratio. A health surveys were used to assess mental and physical improvements of patients as well as other factors. Results: HAQ-S revealed that changes in scores from baseline in both groups were time dependent until 14 weeks and that during the first 4 weeks of treatment the changes declined rapidly. The SF-36 health survey revealed that both HS016 and adalimumab produced rapid beneficial effects against AS during the first 2 weeks of therapy, which gradually declined between 2 and 12 weeks and flattened out after 12 weeks until 24 weeks. Conclusion: This trial demonstrated that both HS016 and adalimumab produced rapid improvements in symptoms during the first 2 weeks of treatment. These findings suggest that HS016 is an alternative economical treatment for Chinese AS patients producing a rapid amelioration of symptoms, aiding them to recover their lifestyle satisfaction. Trial registration: http://www.chictr.org.cn/enindex.aspx, ChiCTR1900022520, retrospectively registered. Key points • HS016 and adalimumab produced rapid AS symptom improvements during the first 2 weeks followed by a slowdown of improvements until week 4 with afterwards few improvements evaluated by HAQ-S • The improvements according to the short form of the 36 (SF-36) questionnaires revealed similar trends as for HAQ-S • There was no significant difference in HAQ-S and SF-36 scores between HS016 and adalimumab [ABSTRACT FROM AUTHOR]

One can also assess the percent of patients achieving a disease state such as CDAI, Simple Disease Activity Scale (SDAI), or DAS28(ESR) remission or low disease activity [[4]]. There have been four properly powered head-to-head RCT in RA comparing a jakinib plus continued methotrexate (MTX) to a TNFi (adalimumab 40 mg every other week plus MTX) in patients with continued disease activity despite MTX. 6652745 29 Huffstutter J, Kafka S, Brent L, Matucci-Cerinic M, Tang K, Chevrier M, Sprabery T, DeHoratius R. Clinical response to golimumab in rheumatoid arthritis patients who were receiving etanercept or adalimumab: results of a multicenter active treatment study. To determine relative efficacy of two molecules, the gold standard is a well-designed head-to-head randomized clinical trial (RCT) comparing the two with a validated and clinically meaningful primary endpoint. [Extracted from the article]

Background: To compare outcomes of a short and long weaning strategy of anti-tumor necrosis factor (aTNF) in our prospective juvenile idiopathic arthritis (JIA) cohort., Research Design and Methods: JIA patients on subcutaneous adalimumab with at least 6 months of follow-up were recruited (May 2010-Jan 2022). Once clinical remission on medication (CRM) was achieved, adalimumab was weaned according to two protocols-short (every 4-weekly for 6 months and stopped) and long (extending dosing interval by 2 weeks for three cycles until 12-weekly intervals and thereafter stopped) protocols. Outcomes assessed were flare rates, time to flare, and predictors., Results: Of 110 JIA patients, 77 (83% male, 78% Chinese; 82% enthesitis-related arthritis) underwent aTNF weaning with 53% on short and 47% on long weaning protocol. The total flare rate during and after stopping aTNF was not different between the two groups. The time to flare after stopping aTNF was not different (p = 0.639). Positive anti-nuclear antibody increased flare risk during weaning in long weaning group (OR 7.0, 95%CI: 1.2-40.8). Positive HLA-B27 (OR 6.5, 95%CI: 1.1-30.4) increased flare risks after stopping aTNF., Conclusion: Duration of weaning aTNF may not minimize flare rate or delay time to flare after stopping treatment in JIA patients. Recapture rates for inactive disease at 6 months remained high for patients who flared after weaning or discontinuing medication., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Objective: SB5 showed comparable efficacy and safety profile in respect to adalimumab originator (ADA) in randomized clinical trials of rheumatoid arthritis (RA) and psoriasis. We aimed to describe the efficacy and safety of SB5 after switching from ADA in RA, axial spondyloarthritis (axSpA), psoriatic arthritis (PsA) and juvenile idiopathic arthritis (JIA) patients. Method: Adult RA, PsA, axSpA, JIA patients treated with ADA for at least 6 months, switched to SB5 in stable clinical conditions, were eligible. Data on safety, activity indexes and patient-reported outcomes were collected at baseline, 3 and 6 months after switching. Results: Eighty-two patients (19 RA, 28 PsA, 32 axSpA and 3 JIA; 45 females, mean age 54 ± 14 years, disease duration 13 ± 7 years, ADA duration 6 ± 3 years) were enrolled. RA patients showed stable conditions, while PsA patients showed an increase in both HAQ, DAS28(CRP) and DAPSA and axSpA patients an increase in VAS pain, VAS patient disease activity and ASDAS, both at 3 months. There were changes in the concomitant medications profile, with regression of activity indexes increases at 6 months. Adverse events were reported by 33.7% patients at 3 months and 16.6% patients at 6 months, mostly disease flares and infectious events. Two patients stopped SB5. Conclusions: Despite temporary changes in the concomitant medication profile for mild disease flares, our real-life data replicate the safety profile of switching from ADA to SB5 in RA, with additional data for its applicability in PsA and axSpA patients, further supporting switching to biosimilars in treating inflammatory rheumatic conditions. Key Points • Switching from adalimumab originator to SB5 is feasible in real life rheumatic inflammatory joint diseases. • Mild disease flares can present after switching from originator adalimumab to SB5, in particular in axial spondyloarthritis and psoriatic arthritis. • Changes in concomitant medications profile allows the control of minor disease flares presenting after switching from adalimumab originator to SB5. [ABSTRACT FROM AUTHOR]

Objective: The goal of this study was to evaluate the long-term impact of adalimumab therapy on work-related outcomes in employed patients with rheumatoid arthritis (RA). Method: We utilized data from an observational cohort of German patients who initiated adalimumab treatment during routine clinical care. Analyses were based on employed patients (part-time or full-time) who continued adalimumab treatment for 24 months. Major outcomes were self-reported sick leave days in the previous 6 months, absenteeism, presenteeism, and total work productivity impairment as assessed by the Work Productivity and Activity Impairment (WPAI) questionnaire and disease activity assessments. The normal number of sick leave days was based on data from the German Federal Statistical Office. Results: Of 783 patients, 72.3% were women, mean age was 47.9 years, and mean disease duration was 7.8 years. At baseline (before adalimumab initiation), 42.9% of patients had higher than normal sick leave days (> 5) in the previous 6 months. During 24 months of adalimumab treatment, 61% of patients with higher than normal sick leave days at baseline returned to normal sick leave values (≤ 5 days/6 months). Overall, mean sick leave days/6 months decreased from 14.8 days at baseline to 7.4 days at month 24. Improvements were observed in WPAI assessments and disease activity measures, although presenteeism levels remained high (32.2% at month 24). Conclusions: Adalimumab treatment was associated with strong and sustained improvements in work-related outcomes in employed patients who continued on adalimumab for 24 months. Presenteeism appears to be the work outcome most resistant to improvement during RA treatment. Trial registration: NCT01076205 Key Points • Long-term adalimumab therapy was associated with sustained improvements in work outcomes in patients with rheumatoid arthritis. • Despite improvements in sick leave days and work absenteeism, presenteeism (impairment while at work) remained relatively high. [ABSTRACT FROM AUTHOR]

A 49-year-old African American male with multiorgan sarcoidosis presented with recurrent episodes of dactylitis and arthritis. Imaging had shown sarcoid osseous involvement of both hands. This would improve temporarily with high-dose corticosteroids but once tapered, he would experience recurrent flares. Despite several different oral immunosuppressant regimens, significant improvement was only observed after the initiation of adalimumab. Not only was adalimumab successful in symptomatic relief, in addition, patient continues to be in remission with no recurrent episodes of dactylitis. Prednisone was successfully tapered from 40 to 3 mg daily. This improvement with TNF inhibitors has been reported with other manifestations of sarcoidosis including pulmonary and ocular involvements. Osseous sarcoidosis is a very rare presentation, and little information regarding treatment with TNF inhibitors is available. TNF inhibitors should be considered as the next-step therapy in resistant cases of osseous sarcoidosis and dactylitis not responding to corticosteroids and traditional immunosuppressant therapy. [ABSTRACT FROM AUTHOR]

Objective: To assess the longitudinal production of anti-adalimumab antibody (AAA) and baseline risk factors for this antibody development in juvenile idiopathic arthritis (JIA) patients initiating adalimumab (ADA). Method: Thirty consecutive JIA patients under ADA therapy were prospectively followed. JIA clinical/laboratorial/treatment data and sera for ADA and AAA assays (ELISA and bridging ELISA) were obtained at baseline (BL), 2 months (2M), 3 months (3M), 6 months (6M), 12 months (12M), and 24 months (24M). Patients with therapy failure requiring ADA withdrawn had their sera evaluated at their last medical visit prior to biologic switch (blinded to ADA and AAA levels). Results: AAA was absent at BL, first detected at 2M after ADA initiation in 2/30 (7%) patients with a significant increase at 3M (10/29 (34%), p = 0.013) and no major change in 6M (11/30 (37%)) and 12M (9/26 (35%)). Of note, at 3M, AAA levels correlated negatively with ADA levels (r = − 0.781, p = 0.0001). Analysis of BL predictors revealed a significantly higher risk of developing AAA in patients with female gender (OR 21; 95% CI 1.08–406.57; p = 0.044), ESR > 30 mm/1st hour (OR 5.44; 95% CI 1.04–28.53; p = 0.045), and leflunomide use (OR 9.33; 95% CI 1.51–57.66; p = 0.016). In contrast, concomitant use of methotrexate was protective for AAA appearance (OR 0.08; 95% CI 0.01–0.53; p = 0.009). After 12M of ADA, 60% of AAA-positive patients required drug switch for drug failure compared with 15% in AAA-negative group (p = 0.03). Conclusions: This study provides novel evidence of AAA production kinetics demonstrating a timely significant increase starting at 3M and stable throughout 24M. We also identified female gender, increased ESR, and leflunomide use as relevant risk factors for AAA production at BL, whereas methotrexate was protective. Early systematic monitoring of AAA at 3M may, therefore, guide drug switching in these patients. Key Points • Anti-adalimumab antibodies (AAA) production kinetics demonstrated a timely significant increase starting at 3M in juvenile idiopathic arthritis (JIA) patients under adalimumab therapy • Female gender, increased ESR, and leflunomide use were identified as relevant risk factors for AAA production in JIA, whereas methotrexate was protective [ABSTRACT FROM AUTHOR]

Objectives: There are no pharmacovigilance studies on adverse event (AE) data for tumour necrosis factor alpha (TNFα) inhibitors in South Korea. We analysed AEs induced by adalimumab, infliximab, and etanercept Methods: We used data from the Korea Institute of Drug Safety and Risk Management–Korea Adverse Events Reporting System Database (KIDS-KD) collected between 2005 and 2016. We used three different signal detection methods: proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC). The drug was compared with drug labels in the USA and Korea. Logistic regression analysis identified AEs that are more likely to occur with drug use. Results: Of the 5594 AEs identified, 350, 452, and 71 were related to adalimumab, infliximab, and etanercept, respectively. We identified seven new signals, which were not listed on drug labels in either Korea or the USA, for AEs associated with the study drugs: two for adalimumab (medication error and drug failure), two for infliximab (palpitation and temperature sensation change), and three for etanercept (hyperkeratosis, acne, and thyroid neoplasm malignant). Injection site pain (OR 6.14, 95% CI 1.15–32.74) and alopecia (OR 4.54, 95% CI 1.16–17.77) for adalimumab, chest pain (OR 6.01, 95% CI 1.35–26.77) for infliximab, and uveitis (OR 10.11, 95% CI 1.13–90.77) for etanercept were more likely to be reported in patients with each TNFα inhibitor than in those without, respectively. Conclusions: Seven new signals that were not included in the current label were identified for TNFα inhibitors and should be updated and monitored. Key Points • Large-scale spontaneous AE reporting data and data mining techniques are useful for detecting signals of rare AEs as well as common AEs induced by drugs. • Drug labels should be updated to reflect signals that are newly discovered by continuous monitoring. [ABSTRACT FROM AUTHOR]

Objectives: To compare the safety, efficacy, and immunogenicity of MSB11022 (acetate-buffered formulation), an adalimumab biosimilar, with the reference product. Method: AURIEL-RA study was a phase 3, multicenter, randomized, double-blind, parallel group trial (NCT03052322). Patients with moderately-to-severely active rheumatoid arthritis (RA) with an inadequate response to methotrexate were randomized 1:1 to MSB11022 or reference adalimumab. The primary endpoint was the incidence of treatment-emergent adverse events of special interest (AESIs) (predefined as hypersensitivity) up to week 52. The key secondary endpoint was ACR20 (≥ 20% improvement in American College of Rheumatology core set measurements from baseline) at week 12. Other efficacy endpoints, quality of life, immunogenicity, and pharmacokinetic parameters were evaluated up to week 52. Secondary safety endpoints were evaluated up to week 52 and at a 4-month safety follow-up. Results: In total, 288 patients were randomized. The proportion of patients experiencing ≥ 1 treatment-emergent AESI up to week 52 was similar between trial arms: 6 patients (4.2%; 95% CI 1.56, 8.91) receiving MSB11022, and 8 patients (5.5%; 95% CI 2.41, 10.58) receiving reference adalimumab. No clinically meaningful differences in efficacy, quality of life, or immunogenicity were seen between treatment arms up to week 52. No notable difference in the incidence of treatment-emergent adverse events was observed between treatment arms up to the end of the follow-up period. Conclusions: These results suggest MSB11022 and reference adalimumab are similar in patients with moderately-to-severely active rheumatoid arthritis in terms of safety, immunogenicity, and efficacy. AURIEL-RA provides evidence to support the similarity of MSB11022 and adalimumab. Key Points • Incidences of hypersensitivity events were similar for MSB11022 (modified buffer) and reference adalimumab. • There was no difference in local reactions between MSB11022 (modified buffer) and reference adalimumab. • AURIEL-RA confirms the equivalence in efficacy and immunogenicity of MSB11022 (modified buffer) and reference adalimumab. [ABSTRACT FROM AUTHOR]

Our center carried out an extended study to evaluate the influence of HS016 on sacroiliitis and hip arthritis using magnetic resonance imaging (MRI). One patient of the HS016 group discontinued the study because of sepsis, so 13 and 5 patients who received HS016 or its originator therapy underwent the final MRI examinations. [Extracted from the article]

Macrophage activation syndrome (MAS) is a rare and potentially fatal condition characterized by excessive activation and uncontrolled proliferation of T lymphocytes and macrophages, leading to overwhelming systemic inflammation and cytokine release. MAS has been reported with viral infections, autoimmune disorders, malignancies, and medications. We describe a case of a patient with axial spondyloarthritis (axSpA) treated with adalimumab, who presented with MAS. [ABSTRACT FROM AUTHOR]

Dactylitis is a frequent disabling feature of psoriatic arthritis (PsA). Therapeutic strategy on dactylitis is not really codified. We performed a complementary literature review (since a previous one in 2014) of efficacy of new treatments recently used in PsA on this specific clinical manifestation. Eleven publications were retained (4697 patients). In the randomized double-blind placebo-controlled trials analyzed, authors declared ustekinumab, ixekizumab, adalimumab, and apremilast efficient. Secukinumab, clazakizumab, abatacept, and tofacitinib were promising. Brodalumab was ineffective. Calculations of odds ratios for residual dactylitis were significant for clazakizumab 100 mg and secukinumab in anti-TNF-naïve population. Homogenization of dactylitis assessment and use of this criterion as primary outcome are necessary to have better data on treatment efficacy in the future. [ABSTRACT FROM AUTHOR]

The aim of the present study was to compare long-term adalimumab (ADA) and infliximab (IFX) retention rates in patients with intermediate, posterior, or panuveitis. Additional aims are as follows: (i) to identify any difference in the causes of treatment discontinuation between patients treated with ADA and IFX; (ii) to assess any impact of demographic features, concomitant treatments, and different lines of biologic therapy on ADA and IFX retention rates; and (iii) to identify any correlation between ADA and IFX treatment duration and the age at uveitis onset, the age at onset of the associated systemic diseases, and the age at the start of treatment. Clinical, therapeutic, and demographic data from patients with non-infectious intermediate, posterior, or panuveitis treated with ADA or IFX were retrospectively collected. Kaplan-Meier plot and log-rank (Mantel-Cox) test were used to assess survival curves. One hundred eight patients (188 eyes) were enrolled; in 87 (80.6%) patients, uveitis was associated with a systemic disease. ADA and IFX were administered in 62 and 46 patients, respectively. No statistically significant differences were identified between ADA and IFX retention rates (p value = 0.22). Similarly, no differences were identified between ADA and IFX retention rates in relation to gender (p value = 0.61 for males, p value = 0.09 for females), monotherapy (p value = 0.08), combination therapy with conventional disease-modifying antirheumatic drugs (log-rank p value = 0.63), and different lines of biologic therapy (p value = 0.79 for biologic-naïve patients; p value = 0.81 for subjects previously treated with other biologics). In conclusion, ADA and IFX have similar long-term retention rates in patients with non-infectious intermediate, posterior, and panuveitis. Demographic, clinical, and therapeutic features do not affect their long-term effectiveness. [ABSTRACT FROM AUTHOR]

The primary aim of the study was to evaluate the efficacy of tumor necrosis factor (TNF)-α blockers adalimumab (ADA) and infliximab (IFX) in refractory sight-threatening retinal vasculitis (RV) during a 12-month follow-up period. Secondary aims were to evaluate (i) any impact of concomitant conventional disease-modifying anti-rheumatic drugs (cDMARDs) and different lines of biologic therapy; (ii) any difference in terms of efficacy between ADA and IFX; (iii) consequences of biotherapies on the best-corrected visual acuity (BCVA); (iv) corticosteroid-sparing effect; and (vi) ocular complications during anti-TNF-α treatment. Demographic, clinical, and therapeutic data were retrospectively collected from the medical records and statistically analyzed. Forty-eight patients (82 eyes) were recruited, 22 (45.8%) of which received IFX and 26 (54.2%) ADA. The percentages of patients achieving RV remission within 3 and 12 months were 54 and 86%, respectively. A significant decrease in RV detection was identified from baseline to 3-month (p < 0.0001) and 12-month (p < 0.0001) assessments and between 3-month and 12-month visits (p = 0.004). No differences were identified in terms of RV resolution between (i) patients undergoing monotherapy and those co-administered with cDMARDs at 3-month (p = 0.560) and 12-month (p = 0.611) follow-up; (ii) biologic-naïve patients and those already exposed to other biologics at 3-month (p = 0.497) and 12-month (p > 0.99) visits; and (iii) patients treated with ADA and those treated with IFX (p = 0.357). During the study period, a statistically significant corticosteroid-sparing effect was observed (p = 0.0002), while BCVA values did not significantly change (p = 0.950). Anti-TNF-α monoclonal antibodies have proved excellent results in patients with recalcitrant sight-threatening RV. [ABSTRACT FROM AUTHOR]

To identify clinical variables capable of predicting long-term treatment duration of TNF-α inhibition in patients with Behçet’s disease (BD)-related uveitis. Demographic, clinical, and therapeutic data were retrospectively collected from BD patients treated with the tumor necrosis factor (TNF)-α blockers infliximab and adalimumab. Patients still continuing TNF-α inhibitors at 48-month follow-up visits were classified as long-term responders and were statistically compared to patients discontinuing treatment before the 48-month visit. Forty-five patients (75 eyes) were enrolled. Thirty-two patients continued anti-TNF-α treatment for more than 48 months; 13 patients discontinued the treatment after a mean time of 12.3 ± 10.44 months due to lack (61.5%) or loss (38.5%) of efficacy. Baseline value of BD current activity form was the only variable discriminating long- and short-term responsive patients (p = 0.048, OR = 0.656, C.I. 95% 0.433-0.996). Disease activity levels at the start of treatment predict duration of response to monoclonal TNF antagonists in ocular BD. [ABSTRACT FROM AUTHOR]

Adalimumab is a TNF-α blocker antibody similar in structure and function to natural human IgG1. Even if adalimumab is fully humanized, the development of anti-drug antibodies has been reported in several inflammatory conditions. The objective of our study was to assess the presence of anti-adalimumab antibodies (AAA) and their clinical relevance in a cohort of juvenile idiopathic arthritis (JIA) patients on adalimumab. This is a prospective observational cohort study recruiting JIA children. Experiments were performed using a validated surface plasmon resonance (SPR)-based optical assay (Biacore® T100). Disease activity was evaluated using the Juvenile Arthritis Disease Activity Score with 10 joint count (JADAS-10). The Mann-Whitney U test, Wilcoxon signed-rank test for paired samples, chi-square, and Fisher exact test were used to compare data. Pearson’s and Spearman’s correlation tests were used to determine correlation coefficients for entered variables: demographic, clinical, and serological data. Ten (37%) out of 27 patients included in the study had at least one AAA-positive sample. Patients developed AAA between 3 and 38 months after starting adalimumab. Seven (70%) out of 10 children with AAA positivity experienced at least a relapse compared to 4 (23.5%) out of 17 AAA-negative children (rs 0.45, p < 0.017). In conclusion, using an innovative and accurate assay method, we found a high incidence of anti-drug antibodies in a cohort of adalimumab-treated JIA patients observed over a mean period of 40 weeks; the presence of anti-adalimumab antibodies seemed to be related to the number of relapses. [ABSTRACT FROM AUTHOR]

We aimed to assess the relative efficacy and safety of biosimilar adalimumab and originator adalimumab plus methotrexate (MTX) compared to those of placebo plus MTX in patients with active rheumatoid arthritis (RA) who showed an inadequate response to MTX. We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) examining the efficacy and safety of biosimilar + MTX and adalimumab + MTX versus placebo + MTX (MTX group) in patients with active RA despite treatment with MTX. A total of eight RCTs involving 2543 patients met the inclusion criteria. The ACR20 response rate was significantly higher in the biosimilar + MTX (odds ratio [OR] 2.91, 95% credible interval [CrI] 1.57-5.74) and adalimumab + MTX (OR 2.80, 95% CrI 1.81-4.46) groups than in the MTX group, with no difference in the ACR20 response rate between the biosimilar + MTX and adalimumab + MTX groups. Biosimilar + MTX had the highest probability of being the best treatment in terms of the ACR20 response rate (surface under the cumulative ranking curve [SUCRA] = 0.7896), followed by adalimumab + MTX (SUCRA = 0.7082) and MTX (SUCRA = 0.0022). The ACR50 and ACR70 response rates showed a distribution pattern similar to that of the ACR20 response rate. Safety based on the number of serious adverse events did not differ significantly among the three interventions in the follow-up period of 12 to 24 weeks. Biosimilar and originator adalimumab, in combination with MTX, represent an effective intervention for active RA despite treatment with MTX. No significant difference was found between biosimilar and originator adalimumab in terms of efficacy and safety. However, follow-up in RCTs is short and not all safety outcomes can be assessed in RCTs. Thus, additional long-term evaluations are needed. [ABSTRACT FROM AUTHOR]

Weekly adalimumab dosing is used to treat juvenile idiopathic arthritis (JIA), uveitis, and other pediatric rheumatic diseases, but the safety of such dosing has not previously been studied. A retrospective chart review was conducted to assess the safety of weekly adalimumab. Demographic and clinical data were collected. Basic descriptive analysis was performed to assess for adverse events from weekly adalimumab. Sixty-nine patients at the University of Minnesota or Gillette Children's Hospital were identified as treated with weekly adalimumab. Sixty (87%) were eligible for the chart review. Weekly adalimumab was used most commonly to treat uveitis (28%, 17/60) and rheumatoid factor-negative polyarticular JIA (25%, 15/60). Mean age at the start of weekly dosing was 13.9 years. The majority of patients were concurrently treated with a non-steroidal anti-inflammatory drug and methotrexate. Fifty-three (90%) patients continued weekly dosing for greater than 3 months. The mean duration of weekly adalimumab was 2 years. Throughout the duration of weekly dosing, 24/60 (40%) patients had documented minor infections not requiring antimicrobials and 24/60 (40%) had documented infections requiring antimicrobial treatment. Only three patients (5%) had an infection requiring hospitalization. Two patients (3%) developed autoimmune disease. Laboratory abnormalities and injection site reactions were rare. Weekly adalimumab was used most commonly to treat uveitis and rheumatoid factor-negative polyarticular JIA, and mean duration of weekly dosing was 2 years. Serious adverse events were rare. [ABSTRACT FROM AUTHOR]

This study aims to investigate 1-year hand bone loss (HBL) in early rheumatoid arthritis (RA) patients treated with a methotrexate (MTX) and intra-articular triamcinolone treat-to-target strategy +/− adalimumab and to determine if HBL is associated with radiographic progression after 2 years. In a clinical trial (OPERA) of 180 treatment-naive early RA patients, bone mineral density (BMD) was estimated from hand radiographs with digital X-ray radiogrammetry (DXR) at baseline, after 6 ( n = 90) and 12 months ( n = 70) of follow-up. Baseline and 2-year radiographs were scored according to the Sharp/van der Heijde method. Baseline characteristics and HBL (0-6 months changes in DXR-BMD) were investigated as predictors of structural damage by univariate linear (∆ total Sharp/van der Heijde score (TSS) as dependent variable) and logistic (+/−radiographic progression (∆TSS >0) as dependent variable) regression analyses. Variables with p < 0.10 were included in multivariable models. In 70 patients with available HBL data, HBL was median (interquartile range (IQR)) −1.9 (−3.3; −0.26 mg/cm) in the MTX + placebo group and −1.8 (−3.6; 0.06) mg/cm in the MTX + adalimumab group, p = 0.98, Wilcoxon signed-rank. Increased HBL (compared to general population reference values) was found in 26/37 and 23/33 patients in the MTX + placebo and MTX + adalimumab groups, chi-squared = 0.99. In 90 patients with HBL data and 2-year radiographic data, HBL was independently associated with ∆TSS after 2 years ( β = −0.086 (95% confidence interval = −0.15; −0.025) TSS unit/mg/cm increase, p = 0.006) but not with presence of radiographic progression (∆TSS >0) (OR 0.96 (0.92-1.0), p = 0.10). In early RA patients treated with a methotrexate-based treat-to-target strategy, the majority of patients had increased HBL, irrespective of adalimumab; HBL was independently associated with ∆TSS after 2 years. [ABSTRACT FROM AUTHOR]

Our aim was to evaluate the effectiveness of adalimumab (ADA) during a 24-month study period in patients affected with Behçet's disease (BD). Clinical and therapeutic data from 100 consecutive BD patients treated with ADA were retrospectively collected and statistically analyzed. At 12-week follow-up, ADA induced clinical efficacy in 81 patients, with a mean time to response of 7.63 ± 3.43 weeks; 25 (30.9 %) patients underwent a disease relapse after 22.17 ± 1.57 months, but treatment adjustments allowed a recovery of efficacy in 11 cases. At 24-month follow-up, 67/100 patients were still on ADA therapy despite concomitant treatments. No differences were identified between ADA monotherapy and co-treatment with DMARDs about efficacy ( p = 0.09), time to response ( p = 0.61), relapses ( p = 0.36), and ADA discontinuation ( p = 0.40). No differences existed in patients switched from other tumor necrosis factor (TNF)-α inhibitors about efficacy at 12 weeks ( p = 0.13) and rapidity of response ( p = 0.93) while relapses ( p = 0.01) and ADA discontinuation at 24 months ( p = 0.001) were significantly more common. Adverse events occurred in 10 patients. ADA confirmed its effectiveness in BD. Combination therapy with DMARDs seems not significantly superior to monotherapy. Frequency and time to response for ADA was not conditioned by a previous lack or loss of efficacy to other TNF-α inhibitors, but long-term loss of efficacy seemed more likely in patients switched from other anti-TNF agents. [ABSTRACT FROM AUTHOR]

The aims of this study are to characterize the biological disease-modifying antirheumatic drug (bDMARD) usage patterns in real-life and examine the remission rate of rheumatoid arthritis (RA) patients receiving bDMARDs in routine clinical practice in China. Consenting RA patients (≥18 years) from 15 teaching hospitals and receiving marketed bDMARDs were included. In total, 802 patients (81.3 % women, 49.0 ± 13.9 years) were included; 89.5 % were receiving a combination of bDMARDs and conventional synthetic DMARDs (csDMARDS), whereas 10.5 % were receiving bDMARD monotherapy. Etanercept (including Enbrel® and local brand Yi Sai Pu® and Qiangke®), tocilizumab, adalimumab, and infliximab were used by 66.6 %, 17.0 %, 7.5 %, and 6.6 % patients, respectively. Etanercept was used at a mean weekly dose of 38.2 ± 15.6 mg for 25.5 ± 47.0 weeks and tocilizumab at 94.5 ± 21.9 mg for 4.7 ± 7.5 weeks. Overall rate of remission was 12.6 %, 5.4 % , and 3.5 % based on DAS28, CDAI, and SDAI scores, respectively. Compared with patients receiving bDMARDs for <3 months, those receiving bDMARDs for ≥3 months exhibited significantly lower DAS28 scores ( p < 0.0001), and a significantly higher proportion of patients who received bDMARDs for ≥12 months achieved the treatment goal (remission or low disease activity, 62.5 % vs. 18.3 %, p < 0.0001). Patients receiving combination therapy with csDMARDs exhibited lower DAS28 scores than patients receiving bDMARD monotherapy (4.3 vs. 4.8, p = 0.011). This large-scale real-world study showed that bDMARD usage patterns in routine clinical practice in China were in accordance with international guidelines for RA management despite the short treatment duration. Longer duration of bDMARD usage and combination therapy showed a favored outcome of RA. [ABSTRACT FROM AUTHOR]

The study aim was to evaluate the efficacy of adalimumab (ADA) in a large series of Behçet's disease (BD)-related uveitis. We performed a multicenter retrospective observational study including 40 selected patients (66 eyes) receiving ADA. Clinical data were retrospectively analyzed at baseline, at 3 and 12 months of treatment. Primary end point was reduction of ocular inflammatory flares. Secondary end points were improvement of best corrected visual acuity (BCVA), reduction of macular thickness measured by optical coherence tomography (OCT), reduction in the occurrence of vasculitis assessed by fluorescein angiography (FA), and evaluation of statistically significant differences between patients treated with ADA monotherapy and those undergoing ADA plus DMARDs and in patients firstly treated with ADA compared to patients previously administered with other biologics; ADA steroid sparing effect was also evaluated. During the first 12 months of ADA therapy, the number of flares significantly decreased from 200 flares/100 patients/year to 8.5 flares/100 patients/year ( p < 0.0001). Similarly, BCVA improved if compared to baseline (7.4 ± 2.9 versus 8.5 ± 2.1, p = 0.03). OCT findings significantly improved showing a mean reduction of central macular thickness (CMT) of 27.27 ± 42.8 μm at the end of follow-up ( p < 0.006). FA identified retinal vasculitis in 22 cases at baseline (55%), 8 (20%) cases after 3 months, and in only one (2.5%) case at 12-month follow-up. FA improvement was highly significant at 3- and 12-month follow-up if compared to baseline ( p < 0.0001 and p = 0.006, respectively). ADA is highly effective and safe for the treatment of BD-related uveitis, providing a long-term control of ocular inflammation. [ABSTRACT FROM AUTHOR]

Biologics as therapeutic interventions for human disease represent both a distinctly modern novelty and an echo of ancient, or at least old, medical practice. The similarity lies in the sense that in both the synthetic effort occurs in living organisms (an extract of a plant, animal tissue, or a cell culture) while the difference is apparent in the bioengineering required in modern methods and the corresponding flexibility to customize the therapeutic product. Although the concept of looking to living systems as a source of medically useful compounds either for research or for actual patient care has never vanished, the development of biochemistry and advances in medicinal chemistry made production by total synthesis the standard for a safe, reliable, and commercial drug production at sufficient scale. In this interval was where much of the modern apparatus for approving medical therapies came to be developed, and as such, the most proper extension of the regulatory regime to modern biologics is not entirely obvious. In particular, the notion of generics for off-patent conventional pharmaceuticals and their role in the marketplace with respect to increasing the accessibility of treatment is not congruent with the relationship between what are known as biosimilars and off-patent originating biologics. In this article, we review elements of the scientific basis for challenges in the production, use, and regulation of biosimilars. In light of these advances, we propose suggestions to modify constraints on biosimilar regulations in the interest of patient care and access to therapies. [ABSTRACT FROM AUTHOR]

The TNF inhibitors etanercept (ETA) and adalimumab (ADA) are approved for treating patients older than 2 years with polyarticular juvenile idiopathic arthritis (JIA). Because long-term experience of treating children younger than 4 years is limited, we evaluated the efficacy and safety of ETA or ADA in patients aged 2-4 years. This prospective, long-term, observational registry study documented baseline demographics, clinical characteristics, disease activity parameters, and safety of patients treated with ETA or ADA. Efficacy was determined using the JADAS-10, the JADAS criteria for minimal disease activity (MDA) and remission, and the PedACR response criteria after 3, 6, 12, 18, and 24 months. Between January 2001 and March 2015, 85 patients with polyarticular JIA aged 2-4 years started anti-TNF-α treatment. Seventy-four (54 girls) patients were treated with ETA and 11 (7 girls) with ADA. After 6/12/24 months of treatment, JADAS-MDA was reached by 55/58/58 % of ETA patients and 50/71/66 % of ADA patients. Furthermore, JADAS-Remission was achieved by 35/44/50 % of ETA patients and 16/28/66 % of ADA patients. PedACR 50/70/90 response was achieved by 64/54/41 % of ETA patients and 56/33/22 % of ADA patients at the last treatment observation. Discontinuation because of remission or inefficacy was recorded in 24 (29 %) and 28 (33 %) patients, respectively. Seventy-nine adverse events and four serious adverse events were reported. Administration of ETA and ADA in JIA patients younger than 4 years was efficacious, well tolerated, and safe. Patients younger than 4 years may show marked improvement following anti-TNF-alpha therapy. [ABSTRACT FROM AUTHOR]

The purpose of the study was to estimate the clinical profile of naïve biological patients with rheumatoid arthritis (RA) starting adalimumab through 3-year calendar periods and their clinical outcomes such as drug survival and global clinical disease control (GCDC). RA patients starting adalimumab as first biological drug between 2003 and 2012 were subdivided in 3-year calendar periods. Survival on therapy was estimated using the Kaplan-Meier analysis. One and 2-year clinical response was assessed by calculating percentage of patients attaining GCDC (28-joint Disease Activity Score (DAS28) ≤ 2.6 + Health Assessment Questionnaire (HAQ) ≤ 0.5), low disease activity (DAS28 ≤ 3.2), remission (DAS28 ≤ 2.6) and good European League Against Rheumatism (EULAR) response. Multivariate regression models were used to assess baseline predictors of drug discontinuation or achievement of clinical remission. We recruited 1695 RA patients. Overall drug persistence at 3 years was 40.6 %, while the global rate of nonswitching patients was 54.7 %. Compared to 2003-2005, initiators in more recent years had a significantly lower 3-year crude drug retention rate (log rank, p < 0.0001) and a significantly higher rate of switching to alternative biologics (log rank, p < 0.0001). No difference in adverse events or effectiveness rate among the calendar periods was found. A substantial proportion of patients (up to 27 %) achieved GCDC at 2 years, regardless of the calendar period. In real-life setting, RA patients starting adalimumab in more recent years had a higher rate of drug discontinuation not related to ineffectiveness or side effects but to switching, probably due to a wider availability of biologics. A meaningful proportion of patients attained GCDC without any difference across calendar periods. [ABSTRACT FROM AUTHOR]

To evaluate the impact of anti-TNF-α therapy on the body weight of rheumatoid arthritis (RA) patients following 24 months of treatment. Data were collected on all RA patients included in the Veneto Region's Registry of Biological Therapy from January 2007 to July 2012. Inclusion criteria were: start of monotherapy with adalimumab, etanercept, or methotrexate, no previous use of biologic therapy, and at least 24 months of treatment. At baseline, 12, and 24 months, each patient completed a questionnaire about physical activity, smoking, alcohol, and food habits. One hundred and thirty-one RA patients in monotherapy with etanercept ( n = 47), adalimumab ( n = 44), and methotrexate ( n = 40) were enrolled for this study. After 24 months of therapy, there was an increase of weight only in patients treated with anti-TNF-α. Patients on etanercept and adalimumab therapy showed a risk to gain weight six times greater compared to those on methotrexate therapy. The results of present study show that the use of anti-TNF-α in RA patients can be associated to a significant increase of body weight. This increase is not shown in patients under treatment with methotrexate. A more careful evaluation of weight changes needs to be considered in RA patients under anti-TNF-α treatment. [ABSTRACT FROM AUTHOR]

The relationship between ankylosing spondylitis and the recently proposed entity called axial spondyloarthritis with its radiographic and non-radiographic forms that have been defined by the Assessment of Spondyloarthritis International Society (ASAS) criteria for axial spondyloarthritis (axSpA), is currently being debated. The Food and Drug Agency (FDA) had criticized the ASAS criteria and the studies which used these criteria to enroll patients in a clinical trial of certolizumab and adalimumab for the treatment of non-radiographic axial spondyloarthritis. The primary aim of classification criteria is to create homogenous patient populations for basic and clinical research. But the multi-arm construct of the ASAS criteria is a potential source of heterogeneity reducing their utility. Criteria sets should be regarded as dynamic concepts open to modifications or updates as our knowledge advances. We provide evidence to conclude that it is time to modify the ASAS Criteria for axSpA, and we propose some of the steps that can be taken to start moving forward in improving the validity of these criteria. [ABSTRACT FROM AUTHOR]

Conversions and reversions of interferon-gamma (IFN-γ) release assays (IGRAs) were observed when these tests were repeated over time in the same individuals, including those treated with biological agents. In most studies, the variability of IFN-γ plasma levels was not paralleled by clinical change, but a few exceptions exist, in which IGRA conversion predicted the emergence of active tuberculosis (TB). We report the case of a Peruvian patient with rheumatoid arthritis (RA) and Crohn's disease scheduled for treatment with adalimumab. TB screening demonstrated latent TB infection (LTBI), and the patient was started on isoniazid (INH) for 9 months. Adalimumab was initiated after 1 month since INH. QuantiFERON-TB Gold In-Tube, one of the IGRAs currently available, was serially repeated to monitor the status of TB infection during treatment with the biological agent. The patient developed active TB preceded by progressively rising levels of released IFN-γ. We came to know that she had withdrawn INH after 2 months on her own initiative. Considering the low rate of INH completion, serial IGRAs may help in the clinical vigilance during prophylaxis as well as anti-TNF treatment, at least in patients presenting other risk factors aside from the state of immunosuppression. [ABSTRACT FROM AUTHOR]

The objective of the study was to combine ultrasonographic (US) with clinical findings for comparing the effect of adalimumab (ADA) to methotrexate (MTX) on the thickness of tendons and enthesis in psoriatic arthritis (PsA) patients. Forty-three consecutive PsA patients were examined at baseline and after 6 and 12 weeks of treatment with ADA or MTX. The US assessment included thickness measurement of the extensor (ET) and flexor tendons (FT) of the second and third finger of both hands, plantar aponeurosis (PA) and the Achilles tendon (AT) bilaterally. Disease activity (DA) was assessed by the number of tender (TJ) and swollen joints (SJ), the number of inflamed enthesis (IE), pain assessment (PAI), and patient (PDAI) and physician (PHDAI) disease activity evaluations by visual activity score (VAS). Nineteen patients received MTX and 24 patients received ADA. All DA parameters improved in both groups. A decrease in thickness of tendons and enthesis was observed only in the ADA group, reaching a level of significance for the left AT ( p = 0.01), left PA ( p = 0.007), the second left FT ( p = 0.04) and the third ET ( p = 0.04). ADA patients showed a trend towards a better response to treatment compared to MTX patients that reach significance at week 6 of treatment for the thickness of left AT ( p = 0.04), left PA ( p = 0.03), the number of TJ ( p = 0.0136), PAI ( p = 0.0028), and PDAI ( p = 0.029). ADA treatment for PsA compared to MTX significantly improved signs of DA and several US parameters. US assessment of enthesis can be an additional useful tool in the monitoring of psoriatic enthesopathy. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality attributed to traditional cardiovascular risk factors and/or the chronic systemic inflammation. We investigated the effect of a TNF antagonist (adalimumab-ADA) on aortic stiffness in RA patients. We studied 18 RA patients with active disease despite therapy with disease modifying antirheumatic drugs (DMARDs), treated with ADA (alone or in combination with DMARDs) for 12 weeks. Disease activity markers as well as aortic stiffness indices (carotid-femoral pulse wave velocity-PWV, augmentation index-AIx), were measured at baseline and at the end of treatment. Eighteen RA patients treated with methotrexate (MTX) were included as controls. Patients were categorized as responders (decrease of Disease Activity Score-DAS28 > 1.2) or nonresponders. There was a statistically significant decrease in PWV (from 8.18 ± 2.03 to 7.01 ± 1.78 m/s, p = 0.00006) and DAS28 (from 6.65 ± 1.22 to 4.69 ± 1.46, p = 0.00007) in RA patients treated with ADA. The decrease in PWV was observed both in responders ( n = 12) and nonresponders ( n = 6). Multivariate analysis showed that the decrease of PWV was independent of changes in disease activity or other parameters. There was no significant change in PWV in patients treated with MTX (from 8.87 ± 1.91 to 8.41 ± 2.17, p = 0.29). No significant change in AIx or traditional cardiovascular risk factors was observed. Treatment with ADA significantly reduced aortic stiffness in RA patients regardless of their response to therapy. These findings imply a direct protective effect of ADA in vascular wall in RA patients. [ABSTRACT FROM AUTHOR]

The objective of this study was to assess the safety of adalimumab in patients aged 2 to <4 years old or ≥4 years old weighing <15 kg with moderately to severely active polyarticular juvenile idiopathic arthritis (JIA). Clinical effectiveness and pharmacokinetics (PK) of adalimumab were also evaluated. This was an international, multicenter, open-label, phase 3b study in 32 patients with active JIA that were treated with adalimumab 24 mg/m (maximum = 20 mg/dose) every other week up to 120 weeks, with or without concomitant methotrexate. Adverse events (AEs) were summarized for completed visits. Efficacy endpoints included American College of Rheumatology pediatric (PedACR) 30/50/70/90 responses and JIA core components. Adalimumab serum trough concentrations were measured in a subset of patients. Among the patients, 88 % were female. Baseline mean age, weight, and JIA duration were 3 years, 13 kg, and 12 months, respectively; 39 % had elevated C-reactive protein. AE incidence rates included any AEs (29/32, 91 %), serious AEs (5/32, 16 %), infectious AEs (25/32, 78 %), and serious infections (3/32, 9 %). No deaths, malignancies, or opportunistic infections were reported. Growth was not adversely impacted. At week 96, 92 % of patients achieved PedACR30, and 77 % achieved PedACR70. Improvements in JIA core components were observed. Mean steady-state serum adalimumab trough concentrations were 7-8 μg/mL at weeks 12 and 24. Adalimumab was well tolerated in JIA patients aged 2 to <4 years old or ≥4 years old weighing <15 kg. The efficacy and PK of adalimumab were comparable to those seen in older JIA patients. [ABSTRACT FROM AUTHOR]