Background: To investigate whether the reason to discontinue the first TNF inhibitor (TNFi) affects the response to the second TNFi in axial spondyloarthritis (axSpA). Methods: Patients with axSpA from the Rheumatic Diseases Portuguese Register (ReumaPt), who discontinued their first TNFi and started the second TNFi between June 2008 and May 2018, were included. Response was assessed by the Ankylosing Spondylitis Disease Activity Score (ASDAS) clinically important improvement (ASDAS-CII), major important improvement (ASDAS-MI), low disease activity (ASDAS-LDA), and inactive disease (ASDAS-ID). The reason for discontinuation of the first TNFi was defined, according to ASDAS-CII as primary failure (no response ≤ 6 months), secondary failure (response ≤ 6 months but lost thereafter), adverse events, and others. The association between the reason for discontinuation of the first TNFi and response to the second TNFi over time was assessed in multivariable generalized equation (GEE) models. Results: In total, 193 patients were included. The reason for discontinuation of the first TNFi did not influence the response to the second TNFi, according to the ASDAS-CII. However, a difference was found with more stringent outcomes, e.g., there was a higher likelihood to achieve ASDAS-ID with the second TNFi for patients discontinuing the first TNFi due to secondary failure (OR 7.3 [95%CI 1.9; 27.7]), adverse events (OR 9.1 [2.5; 33.3]), or other reasons (OR 7.7 [1.6; 37.9]) compared to primary failure. Conclusion: Patients with axSpA with secondary failure to their first TNFi, compared to those with primary failure, have a better response to the second TNFi according to stringent outcomes.

Ulcerating and mutilating variant of carpal tunnel syndrome occurs in longstanding cases of untreated disease. Pa- tients present with painless ulcers of the second and third fingers, accompanied with other cutaneous and sensory changes. These patients are often misdiagnosed as having a Raynaud disease or systemic sclerosis. Clinical assessment is the gold standard for the diagnosis of carpal tunnel syndrome, but hand radiography and electromyography help supporting the diagnosis. The authors present two cases of this ulcerating variant of carpal tunnel syndrome.

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The authors present a case of a 51-year-old woman with clinical diagnosis of mixed connective tissue disease and overlap systemic lupus erythematosus features, with a 6-month history of progressive painless abdominal distension. On examination, evident signs of ascites were present. Both the abdominal-pelvic ultrasound and CT scan confirmed a large amount of ascites. A diagnostic paracentesis was performed, which revealed typical features of chylous ascites (CA). An extensive diagnostic work-up led by a multidisciplinary team was performed, excluding malignancy, cirrhosis, infectious, as well as cardiac and primary lymphatic causes. The patient was kept under surveillance, with dietary therapy and periodic ascitic drainages. The hypothesis of an autoimmune cause for CA was considered by exclusion. Rituximab therapy was initiated and an excellent response was achieved, with reduction of the rate of accumulation of CA and an increase in quality of life of the patient.

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Background:It has been common practice to start a second TNF inhibitor (TNFi) in patients with axial spondyloarthritis (axSpA) who discontinue their first TNFi. It remains unclear if the reason for discontinuation of the first TNFi influences the response to the second.Objectives:To assess if the reason of discontinuation of the first TNFi influences the response to the second TNFi.Methods:Patients with axSpA from the ReumaPt registry, who discontinued their first TNFi and started a second TNFi and who had complete data on Ankylosing Spondylitis Disease Activity Score (ASDAS) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at baseline, 3 and 6 months for their first TNFi were included. Then, they were followed every 6 months up to 12 years. The main outcome was the ASDAS clinically important improvement (ASDAS CII). Secondary outcomes were ASDAS major important improvement (ASDAS MI); ASDAS low disease activity (ASDAS LDA); ASDAS inactive disease (ASDAS ID) and BASDAI 50. The reason for discontinuation of the first TNFi was defined as: i) Primary failure, ASDAS CII was not achieved at 3 or 6 months; ii) Secondary failure, ASDAS CII achieved at 3 or 6 months but lost in ≥1 follow-up visit; iii) Adverse events; iv) Other (e.g. pregnancy, surgery). The response to the first TNFi at 3 and 6 months was compared to the response to the second TNFi at the same visits, adjusting for age, gender and C-reactive protein (CRP). The association between the reason of discontinuation of the first TNFi and response the second TNFi over time was tested in generalized estimating equations (GEE) models, adjusted for age, gender and CRP.Results:In total, 193 patients (53% male, mean age 45 (SD:11) years) were included, with a median follow-up time on the second TNFi of 1.5 years. Patients had a lower response to the second TNFi compared to the first TNFi according to the main outcome (ASDAS CII) at 3 months (41% vs 51%) and 6 months (35% vs 56%). There was an association between the reason to discontinue the first TNFi and response to the second TNFi as defined by the most stringent outcomes (ASDAS MI and ASDAS ID), but not for ASDAS CII (Table). Compared to patients who discontinued their first TNFi due to primary failure, patients were more likely to achieve ASDAS ID with the second TNFi when they discontinued their first TNFi due to secondary failure (OR: 7.3 [(95%CI: 1.9; 27.7]), adverse events (OR: 9.1 [2.5; 33.3]), or other reasons (OR: 7.7 [1.6; 37.9]).Conclusion:In axSpA, response to the second TNFi is worse compared to the first TNFi. Patients with a secondary failure to the first TNFi have a better response to the second TNFi compared to those discontinuing the first TNFi due to primary failure, particularly for most stringent outcomes.Table.Association between the reason for discontinuation of the first TNFi and response to the second TNFiReason to discontinue first TNFi*Outcome for the second TNFiOR (95% CI)ASDAS-CII (N=135)ASDAS-MII (N=135)ASDAS-LDA (N=166)ASDAS-ID (N=166)BASDAI50 (N=147)(ref Primary failure) -Secondary failure1.9 (0.7;4.8)4.8 (1.3;18.2)1.2 (0.6;2.4)7.3 (1.9;27.7)1.4 (0.6;3.0) -Adverse events1.5 (0.6;3.5)2.4 (0.6;9.6)0.9 (0.5;1.7)9.1 (2.5;33.3)1.1 (0.5;2.3) -Other1.0 (0.3;3.8)1.7 (0.1;19.4)1.0 (0.4;2.4)7.7 (1.6;37.9)0.5 (0.1;1.7)*GEE models with the reason of discontinuation of the first TNFi as predictor (reference category: primary failure); all models adjusted for age, gender and C-reactive protein. OR in bold are statistically significant (p<0.05).Disclosure of Interests:Santiago Rodrigues-Manica Speakers bureau: Jansse, MSD, Novartis, Alexandre Sepriano: None declared, Fernando Pimentel dos Santos Speakers bureau: Novartis, Pfizer, Biogen, Vitoria,, Nélia Gouveia: None declared, Anabela Barcelos Speakers bureau: Bene, Eli-Lilly, Pfizer, MSD, Novartis, Jaime Branco Speakers bureau: Vitoria, Miguel Bernardes Speakers bureau: Abbvie, Amgen, Biogen, Eli-Lilly, Glaxo-Smith-Kline, Pfizer, Janssen, Novartis, Raquel Ferreira: None declared, Elsa Vieira-Sousa: None declared, Sofia C Barreira: None declared, Filipe Vinagre: None declared, Raquel Roque: None declared, Helena Santos Speakers bureau: AbbVie, Eli-Lilly, Janssen, Pfizer, Novartis, Nathalie Madeira: None declared, João Rovisco: None declared, Alexandra Daniel: None declared, Sofia Ramiro Grant/research support from: MSD, Consultant of: Abbvie, Lilly, Novartis, Sanofi Genzyme, Speakers bureau: Lilly, MSD, Novartis

Background: To investigate whether the reason to discontinue the first TNF inhibitor (TNFi) affects the response to a second TNFi in axial spondyloartrhtis (axSpA).Methods: Patients with axSpA from the Rheumatic Diseases Portuguese Register (ReumaPt), who discontinued their first TNFi and started a second TNFi between June 2008 and May 2018 were included. Response was assessed by the Ankylosing Spondylitis Disease Activity Score (ASDAS) clinically important improvement (ASDAS-CII), major important improvement (ASDAS-MI), low disease activity (ASDAS-LDA) and inactive disease (ASDAS-ID). The reason for discontinuation of the first TNFi was defined, according to ASDAS-CII as: primary failure (no response ≤6 months); secondary failure (response ≤6 months but lost thereafter); adverse events; other. The association between the reason of discontinuation of the first TNFi and response to the second TNFi over time was assessed in multivariable generalized equation (GEE) models.Results: In total, 193 patients were included. The reason of discontinuation of the first TNFi did not influence the response to a second TNFi, according to the ASDAS-CII. However, a difference was found with more stringent outcomes, e.g. there was a higher likelihood to achieve ASDAS-ID with the second TNFi for patients discontinuing the first TNFi due to secondary failure (OR: 7.3 [(95%CI: 1.9; 27.7]), adverse events (OR: 9.1 [2.5; 33.3]), or other reasons (OR: 7.7 [1.6; 37.9]) compared to primary failure.Conclusion: Patients with axSpA with secondary failure to their first TNFi, compared to those with primary failure, have better response to the second TNFi according to stringent outcomes.