Percival D. Sampaio-Barros

2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis

To update and integrate the recommendations for ankylosing spondylitis and the recommendations for the use of tumour necrosis factor inhibitors (TNFi) in axial spondyloarthritis (axSpA) into one set applicable to the full spectrum of patients with axSpA. Following the latest version of the European League Against Rheumatism (EULAR) Standardised Operating Procedures, two systematic literature reviews first collected the evidence regarding all treatment options (pharmacological and non-pharmacological) that were published since 2009. After a discussion of the results in the steering group and presentation to the task force, overarching principles and recommendations were formulated, and consensus was obtained by informal voting. A total of 5 overarching principles and 13 recommendations were agreed on. The first three recommendations deal with personalised medicine including treatment target and monitoring. Recommendation 4 covers non-pharmacological management. Recommendation 5 describes the central role of non-steroidal anti-inflammatory drugs (NSAIDs) as first-choice drug treatment. Recommendations 6–8 define the rather modest role of analgesics, and disprove glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) for axSpA patents with predominant axial involvement. Recommendation 9 refers to biological DMARDs (bDMARDs) including TNFi and IL-17 inhibitors (IL-17i) for patients with high disease activity despite the use (or intolerance/contraindication) of at least two NSAIDs. In addition, they should either have an elevated C reactive protein and/or definite inflammation on MRI and/or radiographic evidence of sacroiliitis. Current practice is to start with a TNFi. Switching to another TNFi or an IL-17i is recommended in case TNFi fails (recommendation 10). Tapering, but not stopping a bDMARD, can be considered in patients in sustained remission (recommendation 11). The final two recommendations (12, 13) deal with surgery and spinal fractures. The 2016 Assessment of SpondyloArthritis international Society-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA.

The challenge of early systemic sclerosis for the EULAR Scleroderma Trial and Research group (EUSTAR) community. It is time to cut the Gordian knot and develop a prevention or rescue strategy

Early diagnosis of systemic sclerosis (SSc) may allow the start of treatment that could slow disease progression. For this reason early diagnosis of the disease is of pivotal importance. However, the lack of diagnostic criteria and valid predictors significantly limit patient evaluation and the use of potentially effective drugs in the earliest phase of SSc. Early SSc may be suspected on the basis of Raynauds phenomenon, puffy fingers, autoantibodies and SSc capillaroscopic pattern. In practice, the aim is to have criteria for the diagnosis of very early SSc. The criteria that are proposed are obviously provisional and need to be validated: (a) initially through a Delphi technique; (b) thereafter perhaps using already available datasets; but (c) of critical importance, through prospective studies. Only after prospective studies can these potential criteria be considered validated. The consensus on criteria for the classification of very early SSc might be part of the evolving EULAR/ACR project of reclassification of SSc.

Methotrexate in the treatment of ankylosing spondylitis.

The authors carried out an open prospective study analyzing methotrexate (MTX) ef®cacy and toxicity in 34 patients with ankylosing spondylitis (AS) for a period of one year. All the patients presented with active axial disease, characterized by in ̄ammatory spinal pain, prolonged morning stiffness, erythrocyte sedimentation rate (ESR) §25 mm, and failure on treatment with non-steroidal anti-in ̄ammatory drugs for a period of more than two years. MTX was taken at a single weekly intramuscular dose of 12.5 mg. Thirty-one patients (91%) concluded treatment. Eighteen patients (53%) were considered responders to MTX; most of them presented peripheral arthritis. Despite clinical improvement, axial measures were unaltered at the end of the study. The mean value of ESR decreased signi®cantly at the end of the treatment (p~0.0001), predominantly in the responders group. Side effects were observed in 23 patients (68%) and included dyspeptic syndrome, transient elevation of liver enzymes, and dizziness. The results of this one year open study suggest that MTX can be an ef®cient drug in the treatment of AS.The authors carried out an open prospective study analyzing methotrexate (MTX) efficacy and toxicity in 34 patients with ankylosing spondylitis (AS) for a period of one year. All the patients presented with active axial disease, characterized by inflammatory spinal pain, prolonged morning stiffness, erythrocyte sedimentation rate (ESR) > or = 25 mm, and failure on treatment with non-steroidal anti-inflammatory drugs for a period of more than two years. MTX was taken at a single weekly intramuscular dose of 12.5 mg. Thirty-one patients (91%) concluded treatment. Eighteen patients (53%) were considered responders to MTX; most of them presented peripheral arthritis. Despite clinical improvement, axial measures were unaltered at the end of the study. The mean value of ESR decreased significantly at the end of the treatment (p=0.0001), predominantly in the responders group. Side effects were observed in 23 patients (68%) and included dyspeptic syndrome, transient elevation of liver enzymes, and dizziness. The results of this one year open study suggest that MTX can be an efficient drug in the treatment of AS.

Undifferentiated Spondyloarthritis: A Longterm Followup

Objective. To analyze the longterm followup of a series of Brazilian patients with undifferentiated spondyloarthritis (uSpA). Methods. Prospective study analyzing a group of 111 patients with the diagnosis of uSpA, fulfilling the European Spondylarthropathy Study Group and the Amor criteria, who were followed for 5 to 10 years in a single university referral center. Patients had their outcome analyzed at 5, 7, and 10 years. Results. There was a predominance of men (81.1%), white ethnicity (78.4%), and positive HLA-B27 (61.3%), with a mean age at onset of 27.2 years. Twenty-seven patients presented development to ankylosing spondylitis (AS; 24.3%) and 3 to psoriatic arthritis (PsA; 2.7%), while 25 patients (22.5%) went into remission during the followup. Univariate logistic regression analysis revealed that ethnicity, HLA-B27, buttock pain, inflammatory low back pain, ankle involvement, grade I sacroiliitis at the beginning of the study, and the use of sulfasalazine were statistically associated with progression to AS. Multivariate logistic regression analysis revealed that HLA-B27 (p = 0.035, OR 6.720, 95% CI 11.45–39.43) and buttock pain (p = 0.009, OR 6.211, 95% CI 1.591–24.25) were statistically associated with progression to AS. Conclusion. In a longterm followup of 111 Brazilian patients with uSpA, HLA-B27 and buttock pain were significant predictors of progression to a definite disease.

Undifferentiated Spondyloarthropathies: A 2-Year Follow-up Study

Abstract: The aim of the study was to analyse the 2-year follow-up of a series of patients with the diagnosis of undifferentiated spondyloarthropathy (uSpA). A prospective study was carried out analysing 68 patients with symptomatic uSpA who fulfilled the European Spondylarthropathy Study Group (ESSG) criteria for seronegative spondyloarthropathies (SpA) and were aged between 18 and 50 years. Inclusion criteria included inflammatory low back pain (ILBP) (without radiographic sacroiliitis), asymmetric oligoarthritis (predominantly affecting large joints in the lower limbs) and heel enthesopathies (Achilles tendinitis and/or plantar fasciitis). Imaging methods included pelvic radiography (at study entry and after 2 years) and calcaneal radiography (at study entry). There was a predominance of male gender (78%), caucasoid race (72%) and positive HLA-B27 (54%), with a mean age of 31 years and mean disease duration of 5 years. The first disease manifestations were ILBP (49%), asymmetric oligoarthritis (35%) and heel enthesopathies (16%). A positive family history of a definite SpA was mentioned by 9% of the patients. Seventeen patients (25%) scored 5 points in the Amor set of SpA criteria; logistic regression analysis showed that HLA-B27, heel enthesopathy and asymmetric oligoarthritis were significantly associated with Amor criteria ≥6, whereas ILBP was associated with Amor criteria <6. Male sex was associated with heel enthesopathies (p = 0.041) and ankle involvement (p = 0.015). Caucasoid race was associated with ILBP (p = 0.015) and buttock pain (p = 0.047). Positive HLA-B27 was associated with wrist involvement (p = 0.019) and Amor criteria ≥6 (p = 0.001). After a 2-year follow-up the following outcomes were observed: uSpA 75%; disease remission 13%; ankylosing spondylitis 10%; psoriatic arthritis 2%. Logistic regression analysis showed that buttock pain and positive HLA-B27 (trend) were statistically associated with progression to a definite SpA. In conclusion, uSpA can represent a provisional diagnosis in the group of SpA and a systematic follow-up is necessary in order to better establish the different patterns of the disease.

Survival, Causes of Death, and Prognostic Factors in Systemic Sclerosis: Analysis of 947 Brazilian Patients

Objective. To analyze survival, prognostic factors, and causes of death in a large cohort of patients with systemic sclerosis (SSc). Methods. From 1991 to 2010, 947 patients with SSc were treated at 2 referral university centers in Brazil. Causes of death were considered SSc-related and non-SSc-related. Multiple logistic regression analysis was used to identify prognostic factors. Survival at 5 and 10 years was estimated using the Kaplan-Meier method. Results. One hundred sixty-eight patients died during the followup. Among the 110 deaths considered related to SSc, there was predominance of lung (48.1%) and heart (24.5%) involvement. Most of the 58 deaths not related to SSc were caused by infection, cardiovascular or cerebrovascular disease, and cancer. Male sex, modified Rodnan skin score (mRSS) > 20, osteoarticular involvement, lung involvement, and renal crisis were the main prognostic factors associated to death. Overall survival rate was 90% for 5 years and 84% for 10 years. Patients presented worse prognosis if they had diffuse SSc (85% vs 92% at 5 yrs, respectively, and 77% vs 87% at 10 yrs, compared to limited SSc), male sex (77% vs 90% at 5 yrs and 64% vs 86% at 10 yrs, compared to female sex), and mRSS > 20 (83% vs 90% at 5 yrs and 66% vs 86% at 10 yrs, compared to mRSS < 20). Conclusion. Survival was worse in male patients with diffuse SSc, and lung and heart involvement represented the main causes of death in this South American series of patients with SSc.

Immunogenicity and safety of the 2009 non-adjuvanted influenza A/H1N1 vaccine in a large cohort of autoimmune rheumatic diseases

Background Despite the WHO recommendation that the 2010–2011 trivalent seasonal flu vaccine must contain A/California/7/2009/H1N1-like virus there is no consistent data regarding its immunogenicity and safety in a large autoimmune rheumatic disease (ARD) population. Methods 1668 ARD patients (systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic sclerosis, psoriatic arthritis (PsA), Behçets disease (BD), mixed connective tissue disease, primary antiphospholipid syndrome (PAPS), dermatomyositis (DM), primary Sjögrens syndrome, Takayasus arteritis, polymyositis and Granulomatosis with polyangiitis (Wegeners) (GPA)) and 234 healthy controls were vaccinated with a non-adjuvanted influenza A/California/7/2009(H1N1) virus-like strain flu. Subjects were evaluated before vaccination and 21 days post-vaccination. The percentage of seroprotection, seroconversion and the factor increase in geometric mean titre (GMT) were calculated. Results After immunisation, seroprotection rates (68.5% vs 82.9% p<0.0001), seroconversion rates (63.4% vs 76.9%, p<0.001) and the factor increase in GMT (8.9 vs 13.2 p<0.0001) were significantly lower in ARD than controls. Analysis of specific diseases revealed that seroprotection significantly reduced in SLE (p<0.0001), RA (p<0.0001), PsA (p=0.0006), AS (p=0.04), BD (p=0.04) and DM (p=0.04) patients than controls. The seroconversion rates in SLE (p<0.0001), RA (p<0.0001) and PsA (p=0.0006) patients and the increase in GMTs in SLE (p<0.0001), RA (p<0.0001) and PsA (p<0.0001) patients were also reduced compared with controls. Moderate and severe side effects were not reported. Conclusions The novel recognition of a diverse vaccine immunogenicity profile in distinct ARDs supports the notion that a booster dose may be recommended for diseases with suboptimal immune responses. This large study also settles the issue of vaccine safety. (ClinicalTrials.gov #NCT01151644)

Association of Interferon‐ and Transforming Growth Factor β–Regulated Genes and Macrophage Activation With Systemic Sclerosis–Related Progressive Lung Fibrosis

Systemic sclerosis (SSc)–related interstitial lung disease (ILD) is one of the leading causes of mortality. We undertook this study to analyze the gene expression of lung tissue in a prospective cohort of patients with SSc‐related ILD and to compare it with that in control lungs and with 2 prospective clinical parameters in order to understand the molecular pathways implicated in progressive lung disease.

Pulmonary involvement in ankylosing spondylitis.

This is a prospective study analyzing 52 asymptomatic, consecutive patients with ankylosing spondylitis (AS), who submitted to a pulmonary investigation that included plain chest radiography, pulmonary function test (PFT), and thoracic high-resolution computed tomography (HRCT). The results were compared according to sex, race, dorsal spine involvement, thoracic diameter, smoking status, and HLA-B27. There were four patients (8%) with an altered plain chest radiograph. PFT presented a restrictive pattern in 52% of the patients. Thoracic HRCT showed abnormalities in 21 patients (40%), predominantly nonspecific linear parenchymal opacities (19%), lymphadenopathy (12%), emphysema (10%), bronchiectasis (8%), and pleural involvement (8%). Linear parenchymal opacities were associated with a smoking history (p=0.026) and dorsal spine involvement (p=0.032). HLA-B27 was not associated with any abnormality. A lower thoracic diameter was observed in patients with dorsal spine involvement (p=0.0001), restrictive pattern at PFT (p=0.023), and linear parenchymal opacities (p=0.015). The study concluded that nonspecific subclinical pulmonary involvement is frequent in AS.

Gynaecologic history in systemic sclerosis.

Abstract: The aim of the study was to analyse the gynaecologic history of 150 Brazilian patients with systemic sclerosis (SSc) by comparing the outcome of the pregnancies before and after disease onset and in the two clinical variants of SSc, as well as to assess the effects of the pregnancy on the progress of the disease. A retrospective analysis was carried out of 150 female SSc patients, more than 18 years old, who attended the outpatient clinic of the Unit of Rheumatology of the State University of Campinas. The patients were questioned about the number of pregnancies, deliveries (full-term infants, premature births and twins) and fetal deaths (spontaneous abortions and perinatal deaths). These data were subdivided into pregnancies before and after SSc onset. In those gestations started after disease onset the patients were questioned about the evolution of SSc during the pregnancy. The patients were also asked about dyspareunia and the age at menopause. Thirty-two patients (21%) had never been pregnant, and only five of them were considered infertile. One hundred and eighteen patients (79%) had a total of 406 pregnancies, with an average of 3.4 per patient; there were 364 pregnancies before and 42 after SSc onset. There were 58 fetal deaths (14% of the pregnancies), 50 of these occurring before and eight after disease onset; 55 were spontaneous abortions and the other three were perinatal deaths. The fertility rate was higher in the limited SSc (3.6) than in the diffuse SSc patients (3.1), although the percentage of fetal deaths and the evolution of SSc during the pregnancy were similar in the two clinical variants. In the pregnancies that occurred after the onset of SSc, the clinical course remained stable in 72% of the cases, worsened in 14% and improved in 14%. Dyspareunia was mentioned by 49 patients (37% of those with an active sexual life). Menopause was reported by 72 patients, predominantly with limited SSc (61 patients). The fertility rate in the postmenopausal SSc patients was 3.9, similar to that observed in general postmenopausal population in Brazil. The analysis of the gynaecologic history in this series of SSc patients showed no increased risk in infertility or spontaneous abortions. The fertility rate in the two SSc clinical variants was higher than that observed in the local global population. Most of the patients who became pregnant after the onset of SSc showed no signs of worsening during the course of the disease.