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IntroductionAnti-TNF drugs have proven to be effective against spondyloarthritis (SpA), although 30% of patients fail to respond or experience adverse events leading to treatment discontinuation. In rheumatoid arthritis, the presence of anti-drug antibodies (ADA) against the first TNF inhibitor influences the outcome after switching. Our aim was to assess whether the response to a second anti-TNF drug is related to the previous development of ADA to the first anti-TNF drug SpA patients.MethodsForty-two SpA patients began a second anti-TNF drug after failing to respond to the first anti-TNF therapy. Clinical activity was assessed by the Ankylosing Spondylitis Disease Activity Score (ASDAS) at baseline (at the beginning of the first and second anti-TNF therapy) and at 6 months after switching. The drug and ADA levels were measured by ELISA before each administration.ResultsAll patients were treated with anti-TNF drugs and mainly due to inefficacy were switched to a second anti-TNF drug. Eleven of 42 (26.2%) developed ADA during the first biologic treatment. At baseline, no differences in ASDAS were found in patients with or without ADA to the first anti-TNF drug (3.52 ± 1.03 without ADA vs. 3.14 ± 0.95 with ADA, p = 0.399) and to the second anti-TNF drug (3.36 ± 0.94 without ADA vs. 3.09 ± 0.91 with ADA, p = 0.466). At 6 months after switching, patients with previous ADA had lower disease activity (1.62 ± 0.93 with ADA vs. 2.79 ± 1.01 without ADA, p = 0.002) and most patients without ADA had high disease activity state by the ASDAS (25 out of 31 (80.6%) without ADA vs. 3 out of 11 (27.3%) with ADA, p = 0.002).ConclusionsIn SpA the failure to respond to the first anti-TNF drug due to the presence of ADA predicts a better clinical response to a second anti-TNF drug.

Background: Hypophosphatasia (HPP) is an inborn error of metabolism characterized by low levels of serum alkaline phosphatase (ALP). Scarce evidence exists about features that should signal the potential association between hypophosphatasaemia and HPP in adults. The aim of this study is to estimate the prevalence of ALPL variants in subjects with persistent hypophosphatasaemia and determine the associated clinical and laboratory features. For this cross-sectional study, laboratory records of 386,353 subjects were screened by measurement of ALP activity. A total of 85 (0.18%) subjects with persistent hypophosphatasaemia (≥2 serum alkaline phosphatase-ALP-measurements ≤35 IU/L and none > 45 IU/L) were included (secondary causes previously discarded). ALPL genetic testing and a systematized questionnaire to retrieve demographic, clinical and laboratory data were performed. Descriptive analysis and logistic regression models were employed to identify the clinical and laboratory characteristics associated with ALPL variants. Results: Forty subjects (47%) had a variant(s) in ALPL. With regard to clinical characteristics, the presence of an ALPL variant was significantly associated only with musculoskeletal pain (OR: 7.6; 95% IC: 1.9-30.9). Nevertheless, a trend to present more dental abnormalities (OR: 3.6; 95% IC: 0.9-13.4) was observed. Metatarsal stress fractures were also more frequent (4 vs 0; p < 0.05) in this group. Regarding laboratory features, median ALP levels were lower in subjects with ALPL variants (26 vs 29 IU/L; p < 0.005). Interestingly, the threshold of ALP levels < 25 IU/L showed a specificity, positive predictive value and positive likelihood ratio of 97.8, 94.4% and 19.8 to detect a positive ALPL test, respectively. Conclusions: In subjects with persistent hypophosphatasaemia -secondary causes excluded-one out of two presented ALPL variants. Musculoskeletal pain and ALP levels < 25 IU/L are associated with this variant(s). In this scenario, ALP levels < 25 IU/L seem to be very useful to identify individuals with the presence of an ALPL variant.

Background Biological therapies have improved the treatment of Rheumatoid Arthritis (RA) in the last decade. The development of anti-TNF antibodies has been found crucial to drug efficacy and survival. All monoclonal antibodies are immunogenic, whereas the fusion proteins, like Etanercept, have proved to be less immunogenic in several studies. Objectives To assess the survival of 3 anti-TNF agents in a cohort of patients with RA, and to determine if there are differences in the survival of the 3 anti-TNF between patients who develop or not immunogenicity. Methods RA patients, who started Adalimumab (ADA), Infliximab (IFX) or Etanercept (ETN) as first biological treatment in a single center between 2002 to 2010 were included. Clinical and demographic data were collected: sex, age, rheumatoid factor, anti-CCP, disease duration, DMARD co-treatment, DAS28 at baseline, date of start and end of treatment and in the case of ADA and IFX, presence or absence of anti-drug antibodies. No patient with anti-ETN antibodies were identified. The reasons for drug discontinuation were classified as adverse event, administration reaction, inefficacy, remission and other (this included pregnancy, malignancies, lost of follow up, etc). The event was defined as drug discontinuation due to only the first 4 reasons. Cumulative incidence through competitive risk was performed to compare drug survival. Results We studied 177 patients with a mean age of 54,7±14,2 years, 83,1% were women. Out of them, 39% (69) started treatment with IFX, 40,7% (72) with ADA, and 20,3% (36) with ETN. The lowest survival was of IFX with a probability of drug discontinuation of 28,1% at 500 days, and 61,4% at 2000 days (about 5 years), compared to 10,2% at 500 days and 35,5% at 5 years of ADA, and versus 14% at 500 days and 31,5% at 5 years of ETN, which was statistically significant (p=0,0001). Inefficacy was the most common reason for discontinuing IFX and ADA with 32,7% and 31,6% respectively, while 41,2% of patients treated with ETN discontinued treatment for reasons that mainly encompassed pregnancy, malignancies, etc. Of the 69 patients treated with IFX, 43,3% developed anti-IFX antibodies (AIA). Anti-ADA antibodies (AAA) were observed in 15,2% of 72 patients who received ADA. In both drugs was found that drug survival was lower in the presence of anti-drug antibodies, as shown in the following table: Cumulative incidence through competitive risk (probability of drug discontinuation) 500 days 2000 days (5 years aprox.) >3000 days (9 years aprox.) p value Infliximab  No AIA 14,7% 47,6% 52,9% 0,016  With AIA 31,5% 68,5% 86,9% Adalimumab  No AAA 2,5% 11,4% 14,8% 0,006  With AAA 0,0% 57,1% 57,1% When survival was analyzed by subgroups of patients treated with IFX and ADA who had not developed antibodies compared with ETN, IFX still showed the lowest survival (probability of drug discontinuation at 5 years of 47,6%, versus 11,4% of ADA and 31,5% of ETN, p=0,003). Conclusions In our cohort, IFX has proven to be the anti-TNF with ...

Background In psoriatic arthritis (PsA) with peripheral involvement classical DMARDs refractory, the anti-TNF therapy has proven to be effective. In recent years, there are some publications that demostrate the correlation between clinical activity and the anti-drug antibodies (ADA) development in rheumatic diseases such as rheumatoid arthritis (RA) and spondyloarthritis (SpA). To date, there is no studies that reveals theses findings in PsA patients treated with infliximab (Ifx) and adalimumab (Ada). Objectives To evaluate in PsA patients treated with Ifx and Ada wether the development of ADA correlate with clinical activity and biological treatment discontinuation. Methods We studied 37 patients with PsA treated with Ifx and Ada from La Paz University Hospital. Clinical activity was assessed using the Disease Activity Score 28 (DAS28), clinical improvement by the delta-DAS28 and treatment response by EULAR criteria at baseline, at 6 months, at 1 year and at > 2nd years of treatment. Ifx and Ada were administred at standard therapeutic schedule. Serum drug and ADA levels were measured by ELISA. Statistical analysis was performed using SPSS 11.0. Results Of the total of patients, 24/37 (64.9%) were treated with Ifx and 13/37 (35.1%) with Ada, being female 23 (62.1%). The mean age was 55.1 ± 12.3 years and the mean disease duration was 14.4 ± 9.9 years. The average time on biological therapy was 4.4 ± 3.2 years. Most patients received concomitantly classical DMARDs [29/37 (78.3%) with DMARDs vs 8/37 (21.7%) in monotherapy]. At baseline, clinical activity (DAS28) was higher in patients who subsequently not developed ADA (5.1 ± 0.9 without ADA vs 13.4 ± 0.6 with ADA, p = 0.021). Clinical activity (DAS28) tended to be higher in patients with ADA at all studied time points (5.4 ± 1.2 with ADA vs 2.8 ± 1.3 without ADA at 6 months, p = 0.007; 4.0 ± 1.2 with ADA vs 3.0 ± 1.3 without ADA at 1 year, p = 0.144; 2.9 ± 1.3 with ADA vs 2.4 ± 0.4 without ADA a> 2nd year, p = 0.169). Clinical improvement (delta-DAS28) was lower in patients with ADA throughout the study (-1.0 ± 1.6 with ADA vs 2.0 ± 1.4 without ADA at 6 months, p = 0.006, 0.3 ± 1.8 with ADA vs 2.1 ± 1.5 without ADA at 1 year, p = 0.052; 0.9 ± 1.5 with ADA vs 2.7 ± 0.8 without ADA a> 2nd year, p = 0.007). Patients without ADA were classified as responders more frequently based on criteria EULAR [2/5 (40%) with ADA vs. 27/30 (90%) without ADA, p = 0.006]. The median time to drug discontinuation was lower in patients with ADA (4.83 ± 1.6 years with ADA vs 7.93 ± 1.4 years without ADA, p = 0.061). The dose increase was more frequent in patients with ADA [3/6 (50%) with ADA vs 4/31 (12.9%) without ADA, p = 0.053], and in contrast, in patients without ADA was more often performed dose decrease of anti-TNF therapy [0/6 (0%) with ADA vs 15/31 (48.3%) without ADA, p = 0.053]. Conclusions The development of ADA correlates with poorer clinical response and more frequent treatment discontinuation in PsA patients in long-term treatment with Ifx and Ada. Disclosure of Int...