Effectiveness of switching between TNF inhibitors in patients with axial spondyloarthritis: is the reason to switch relevant?

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.

Eligibility criteria for biologic disease-modifying antirheumatic drugs in axial spondyloarthritis: going beyond BASDAI.

OBJECTIVES: To compare definitions of high disease activity of the Ankylosing Spondylitis Disease Activity Score (ASDAS) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in selecting patients for treatment with biologic disease-modifying antirheumatic drugs (bDMARDs). METHODS: Patients from Rheumatic Diseases Portuguese Register (Reuma.pt) with a clinical diagnosis of axial spondyloarthritis (axSpA) were included. Four subgroups (cross-tabulation between ASDAS (≥2.1) and BASDAI (≥4) definitions of high disease activity) were compared regarding baseline characteristics and response to bDMARDs at 3 and 6 months estimated in multivariable regression models. RESULTS: Of the 594 patients included, the majority (82%) had both BASDAI≥4 and ASDAS ≥2.1. The frequency of ASDAS ≥2.1, if BASDAI<4 was much larger than the opposite (ie, ASDAS <2.1, if BASDAI≥4): 62% vs 0.8%. Compared to patients fulfilling both definitions, those with ASDAS ≥2.1 only were more likely to be male (77% vs 51%), human leucocyte antigen B27 positive (79% vs 65%) and have a higher C reactive protein (2.9 (SD 3.5) vs 2.1 (2.9)). Among bDMARD-treated patients (n=359), responses across subgroups were globally overlapping, except for the most 'stringent' outcomes. Patients captured only by ASDAS responded better compared to patients fulfilling both definitions (eg, ASDAS inactive disease at 3 months: 61% vs 25% and at 6 months: 42% vs 25%). CONCLUSION: The ASDAS definition of high disease activity is more inclusive than the BASDAI definition in selecting patients with axSpA for bDMARD treatment. The additionally 'captured' patients respond better and have higher likelihood of predictors thereof. These results support using ASDAS≥2.1 as a criterion for treatment decisions.

Safety of Etanercept in the treatment of rheumatic disease patients with Hepatitis C virus infection.

Hepatitis C virus (HCV) infection is a major public health problem. Because Tumour Necrosis Factor (TNF) seems to have an important role in immune response to HCV infection, suppression by TNFi (TNF inhibitors) may pose a potential worsening of chronic HCV infection. We report our experience with 3 cases of patients with chronic HCV infection and advanced liver disease, with different Rheumatic diseases, treated with a TNFi, etanercept (ETN), for a period ranging from 4 months to 4 years without hepatitis C treatment and, in two of them, concomitant therapy with direct-acting antiviral agents (DAA) and afterwards. Although increasing number of clinical reports support the short-term safety and efficacy of TNFi in patients with HCV, some uncertainties remain regarding long-term. These cases suggests that the risk of HCV reactivation related to TNFi remains low even without concomitant antiviral therapy. Nevertheless, a strict collaboration between rheumatologists and gastroenterologists/hepatologists. Our results also showed a good tolerance and efficacy when used concomitantly the new direct-acting antivirals drugs with ETN.

PORTUGUESE RECOMMENDATIONS FOR THE USE OF BIOLOGICAL THERAPIES IN PATIENTS WITH PSORIATIC ARTHRITIS--2015 UPDATE.

OBJECTIVE: To update recommendations for the treatment of psoriatic arthritis with biological therapies, endorsed by the Portuguese Society of Rheumatology (SPR). METHODS: These treatment recommendations were formulated by Portuguese rheumatologists based on literature evidence and consensus opinion. At a national meeting the 16 recommendations included in this document were discussed and updated. The level of agreement among Portuguese Rheumatologists was assessed using an online survey. A draft of the full text of the recommendations was then circulated and suggestions were incorporated. A final version was again circulated before publication. RESULTS: A consensus was achieved regarding the initiation, assessment of response and switching biological therapies in patients with psoriatic arthritis (PsA). Specific recommendations were developed for several disease domains: peripheral arthritis, axial disease, enthesitis and dactylitis. CONCLUSION: These recommendations may be used for guidance in deciding which patients with PsA should be treated with biological therapies. They cover a rapidly evolving area of therapeutic intervention. As more evidence becomes available and more biological therapies are licensed, these recommendations will have to be updated.

Cardiovascular risk profile in systemic lupus erythematosus and rheumatoid arthritis: a comparative study of female patients.

OBJECTIVE: Premature atherosclerosis is well-documented both in Systemic Lupus Erythematosus (SLE) and in Rheumatoid Arthritis (RA) patients, but cardiovascular (CV) risk is particularly high in lupus women. Although conventional CV risk factors do not fully explain the excessive risk in inflammatory diseases, they remain major contributors to atherosclerosis. The aim of the present study was to investigate whether CV risk factors are differentially associated with SLE and RA. METHODS: One hundred women with SLE, 98 with RA and 102 controls matched on age and without overt CV or renal disease were assessed for the presence of Framingham (hypertension, hypercholesterolemia, low HDL, diabetes, smoking) and other CV risks (atherogenic index of plasma (AIP), insulin resistance, obesity, central obesity, metabolic syndrome, uric acid, sedentarism, hypothyroidism and family history of premature CV disease). RESULTS: Modifiable CV risk factors are highly prevalent and occur more frequently in SLE and RA than in age-matched controls. Some differences in Framingham risk factors were found between SLE and RA, with hypertension being more common in young lupus women, hypercholesterolemia more frequent in RA and low HDL-C more frequent in SLE. However, the estimated 10-year Framingham CHD risk or the Reynolds Risk Score was comparable in both diseases. Although hypercholesterolemia was more frequent in RA, lupus women display a more atherogenic lipid profile, with significantly lower HDL-C levels (56.5±16 mg/dl versus 63.7±18; p=0.005), and more cases above the high risk cutpoints for cholesterol/HDL-C (14% versus 4.1%; p=0.01) and for AIP (15% versus 6.1%; p=0.03). Also, uric acid levels are higher in SLE women (4.8±1.5 mg/dl) than in RA (4.1±1.1 mg/dl), p=0.001. On the other hand, insulin resistance is significantly higher in women with RA as compared with SLE (median HOMA-IR 3.5 [6.4]) versus 0.72 [2.5]; p<0.0001) and the difference remained significant after adjustment for BMI and corticosteroids. CONCLUSIONS: Cardiovascular risk profile is distinct in SLE and RA women and the contribution of traditional CV risk factors to atherogenesis may be different in these two diseases. Prospective studies are necessary to understand how the control of modifiable risks can improve CV outcome in different inflammatory settings.

[Systemic lupus erythematosus and weakness]. / Lúpus eritematoso sistémico e fraqueza muscular.

We report a case of a 13-year old young girl, with Juvenile Systemic Lupus Erythematosus and recent onset of muscle weakness. Investigations lead to the diagnosis of Myasthenia Gravis. The most important causes of muscle weakness in lupus patients are discussed.