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Objectives We evaluated the association of lupus nephritis (LN) and adverse pregnancy outcomes in prospective cohorts of pregnant women with SLE (systemic lupus erythematosus). Methods We conducted a patient-level pooled analysis of data from three cohorts of pregnant women with SLE. Pooled logistic regression models were used to evaluate the association of LN and adverse pregnancy outcomes. Odds ratios and 95% confidence intervals were calculated using a fixed effect model by enrolling cohort. Results The pooled cohort included 393 women who received care at clinics in the United States and Canada from 1995 to 2015. There were 144 (37%) women with a history of LN. Compared to women without LN, those with LN had higher odds of fetal loss (OR: 1.90; 95% CI: 1.01, 3.56) and preeclampsia (OR: 2.04; 95% CI: 1.01, 4.13). Among the 31 women with active nephritis (defined as urine protein ≥ 0.5 g/24 h) there was a higher odds of poor pregnancy outcome (OR: 3.08; 95% CI: 1.31, 7.23) and fetal loss (OR: 6.29; 95% CI: 2.52, 15.70) compared to women without LN. Conclusions In this pooled cohort of women with SLE, a history of LN was associated with fetal loss and preeclampsia. Active nephritis was associated with poor pregnancy outcome and fetal loss.

Low disease activity (LDA)/remission is the target of treatment in patients with psoriatic arthritis (PsA). We assessed the proportions of patients with PsA receiving upadacitinib who achieved LDA/remission over 1 year.This was a post hoc analysis of the double-blind, placebo-controlled SELECT-PsA 1 (also adalimumab-controlled) and SELECT-PsA 2 trials. Treatment targets assessed included LDA/remission defined by Disease Activity in Psoriatic Arthritis (≤ 14/ ≤ 4) and Psoriatic Arthritis Disease Activity Scores (≤ 3.2/ ≤ 1.9), as well as minimal disease activity (MDA)/very low disease activity (VLDA) states (5/7 and 7/7 components, respectively, of MDA criteria). Targets were assessed at 24 and 56 weeks. For binary outcomes, non-responder imputation was used for missing data. Data from patients receiving upadacitinib 30 mg was not included in the analysis.Overall, 1386 patients were analyzed. Disease control (i.e., LDA/MDA) was achieved at 24 weeks in upadacitinib 15 mg-treated patients across both studies: LDA/MDA was achieved by 25-48% of patients receiving upadacitinib 15 mg versus 2-16% of patients receiving placebo, and remission/VLDA rates were 7-14% with upadacitinib 15 mg versus 0-4% with placebo. The proportions of patients achieving treatment targets were numerically similar to upadacitinib 15 mg and adalimumab. All responses were sustained at 56 weeks.Remission and LDA are feasible targets with upadacitinib treatment in patients with PsA.ClinicalTrial.gov identifiers NCT03104400 (SELECT-PsA 1) and NCT03104374 (SELECT-PsA 2).Psoriatic arthritis is a disease that causes inflammation of the skin and joints. Doctors measure how bad a patient’s disease is by measuring signs and symptoms of the disease, and using these to make a “score.” The aim of treatment is to reduce the score to low levels (known as “low disease activity”) or very low levels (“remission”). This study looked at results from two clinical trials that compared upadacitinib, a medicine used to treat psoriatic arthritis, with no medicine (placebo) to see how many patients had low disease activity or were in remission after 1 year of treatment. The results showed that more patients who were taking upadacitinib had low disease activity or were in remission after the first 6 months of treatment compared with those who took placebo. This difference between upadacitinib and placebo could still be seen after 1 year of treatment. These results show that treatment with upadacitinib is effective enough for some patients with psoriatic arthritis to achieve low disease activity or remission and to stay at this level, even after more than 1 year of treatment.

Psoriatic arthritis (PsA) is an immune-mediated disease characterized by pain, stiffness, and swelling of peripheral joints, with an estimated prevalence in Canada of 0.45%. Treatment aims to minimize disease activity, reduce progression of damage, and improve quality of life. Secukinumab is a biologic disease-modifying antirheumatic drug (bDMARD) that has demonstrated efficacy and safety for PsA in clinical trials, however there is limited real-world evidence on its use in Canada. The objective of this study was to use the Canadian Spondyloarthritis (CanSpA) Research Network to describe realworld retention and effectiveness of secukinumab among Canadian patients with PsA.Observational cohort study of Canadian PsA patients 18-65 years who attended a clinic of the CanSpA network and received treatment with secukinumab. Patients were indexed on the date they first initiated secukinumab. Retention was assessed at 12-months post-index. Clinical effectiveness was measured as proportion in remission and change in disease activity from baseline to 12-months using several clinical indices.213 patients were included. Overall retention was estimated at 73.6% at 12-months (81.8% for bt/sDMARD-naive patients). 17/110 (15.5%) patients were in DAPSA28-based remission, and 10/70 (14.3%) were in PASDAS-based remission at 12-months. PASI improved by 65.8%; TJC68 and SJC66 improved by 65.5% and 73.7%, respectively.This is the first nationwide study to describe real-world use of secukinumab in Canada for PsA, and supports its effectiveness in a Canadian real-world setting. The CanSpA network represents a unique opportunity to build and improve the real-world evidence base for SpA treatment in Canada.

Owing to recent advances in the recognition of psoriatic arthritis, its outcomes, its pathogenesis, and the development of several novel therapeutic approaches, it is believed that a comprehensive textbook on psoriatic arthritis was necessary. This book will provide the most up-to-date information in the advances in the field of psoriatic arthritis, its classification criteria, and mechanisms of bone destruction and formation. This chapter provides an overview of the scope of the textbook, the rationale behind writing a volume on this subject, and advice to clinicians.

Although there is still some controversy about the existence of psoriatic arthritis (PsA) as a specific form of inflammatory arthritis associated with psoriasis, epidemiological and clinical studies support the unique features of PsA. Because of lack of diagnostic or classification criteria, the disease has been thought of as uncommon. New classification criteria should facilitate case definition of PsA. Over the past several decades, it has become clear that the disease leads to serious disability and even increased mortality. Traditional medications have not been effective in preventing the progression of joint damage. New medications, including biologics, have emerged with potential to controlling the inflammation and arresting the progression of joint damage.

[This corrects the article on p. e1001195 in vol. 6.].

Introduction Systemic lupus erythematosus is a genetically complex disease. Currently, the precise allelic polymorphisms associated with this condition remain largely unidentified. In part this reflects the fact that multiple genes, each having a relatively minor effect, act in concert to produce disease. Given this complexity, analysis of subclinical phenotypes may aid in the identification of susceptibility alleles. Here, we used flow cytometry to investigate whether some of the immune abnormalities that are seen in the peripheral blood lymphocyte population of lupus patients are seen in their first-degree relatives. Methods Peripheral blood mononuclear cells were isolated from the subjects, stained with fluorochrome-conjugated monoclonal antibodies to identify various cellular subsets, and analyzed by flow cytometry. Results We found reduced proportions of natural killer (NK)T cells among 367 first-degree relatives of lupus patients as compared with 102 control individuals. There were also slightly increased proportions of memory B and T cells, suggesting increased chronic low-grade activation of the immune system in first-degree relatives. However, only the deficiency of NKT cells was associated with a positive anti-nuclear antibody test and clinical autoimmune disease in family members. There was a significant association between mean parental, sibling, and proband values for the proportion of NKT cells, suggesting that this is a heritable trait. Conclusions The findings suggest that analysis of cellular phenotypes may enhance the ability to detect subclinical lupus and that genetically determined altered immunoregulation by NKT cells predisposes first-degree relatives of lupus patients to the development of autoimmunity.

Development of treatment recommendations for arthritis has traditionally relied on the compilation of evidence-based data by experts in the field despite recommendations by various bodies for broad stakeholder input. Our objectives were: (1) To develop evidence-based treatment recommendations for the management of spondyloarthritis (SpA) in Canada that also incorporate the perspective of multiple stakeholders. (2) To generate a procedural template for the multidisciplinary development of treatment recommendations.The process was directed by a steering committee comprising the SPARCC Executive, rheumatologists from academic and community-based practice, patient consumers, and a representative from the John Dossetor Health Ethics Centre. Guidelines established by EULAR and stipulated in the AGREE instrument were followed. First, a working document was drafted that included a referenced summary of the evidence-based data and the 12 national arthritis care standards developed by the Alliance for the Canadian Arthritis Program. Second, a Web-based survey was conducted among patient consumers to address the relevance to patients of 2 primary outcome instruments that assess the effectiveness of treatment. Third, a list of questions was generated for drafting propositions by the ethics consultant. A Delphi consensus exercise was then conducted.Consensus was generated on a final list of 38 treatment recommendations categorized under the subject headings of general management principles, ethical considerations, target groups, definition of target disease, disease monitoring, and specific management recommendations.Using broad stakeholder input, we provide treatment recommendations to guide clinical practice and access to care for patients with SpA in Canada.

o determine if the variability of the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), along with the Adjusted Mean SLEDAI-2K (AMS), can better predict major outcomes in SLE than the AMS alone.Patients were followed in the Lupus Clinic at 2-6 month intervals. Clinical and laboratory information necessary to compute the SLEDAI-2K and Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index was collected prospectively and entered onto a computerized database. Patients followed for a minimum of 3 visits, and without absence for a period18 consecutive months, were included in the study. Six different approaches to measure variability of SLEDAI-2K were evaluated for each visit, along with AMS. Approaches were the standard deviation, the slope, average rate of change by visit, the range, the coefficient of variation, and the Percentage of the visits with a change in SLEDAI-2Kor = 3. The SLE outcomes under study were death, presence of damage, coronary artery disease (CAD), and osteonecrosis (ON). The predictability of each outcome was evaluated through time-dependent covariate survival analyses. Regression models included other known major risk factors such as sex, age at diagnosis, SLEDAI-2K at presentation, and disease duration.Five hundred seventy-five patients seen from 1970 to 2002 were included. The average time between visits was 4.0 +/- 2.2 months. Eighty-five patients died, 325 developed damage, 55 had CAD, and 68 had ON. None of the 6 variability measures added more statistical significance in the prediction of any of the 4 outcomes. For the prediction of survival, AMS [hazard ratio (HR) = 1.16, p0.0001] and age at diagnosis (HR 1.05, p0.0001) were the only significant risk factors. For presence of damage, AMS (HR 1.06, p0.0001), age at diagnosis (HR 1.02, p = 0.0004), and disease duration (HR 1.05, p0.0001) were predictors. CAD was predicted by AMS (HR 1.12, p = 0.0003), male sex (HR 2.31, p = 0.02), age at diagnosis (HR 1.06, p0.0001), and disease duration (HR 1.10, p0.0001). For ON, SLEDAI-2K at presentation (HR 1.04, p = 0.003) and disease duration (HR 0.92, p = 0.05) were significant risk factors.Multivariate analysis revealed that AMS, independent of variability of the SLEDAI-2K, is an important predictor of major outcomes in SLE.

To examine the effect of infliximab on employment status, time lost from work, and productivity in a double-blind, placebo-controlled study of patients with active psoriatic arthritis (PsA).Two hundred adult patients with PsA were randomized to intravenous infusions of either infliximab 5 mg/kg or placebo at Weeks 0, 2, 6, 14, and 22, with early escape at Week 16. Employment status, workdays missed, and productivity were assessed at baseline and at Week 14. The effect of PsA on daily productivity was assessed using a visual analog scale.At baseline, similar percentages of patients in both treatment groups were employed and similar percentages missed workdays; the mean productivity score at baseline was similar between groups (roughly 3 on a scale of 0 to 10). At Week 14, median productivity increased significantly in the infliximab group compared with the placebo group (67.5% vs 9.2%; p0.0001). Compared with the placebo group, higher proportions of patients in the infliximab group improved employment status from unemployed at baseline to employed at Week 14 (11.5% vs 0%; p = 0.084) and from part-time to full-time employment (30.0% vs 10.0%; p = 0.582). Among patients employed at baseline and Week 14, a lower proportion of patients in the infliximab group than in the placebo group had missed workdays in the 4 weeks prior to Week 14 (p = 0.138).After 14 weeks of treatment, infliximab improved productivity in patients with active PsA. There was also a trend toward increased employment and reduced time lost from work for patients treated with infliximab.

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activation has been shown to play a role in suppressing angiogenesis and inflammation, both important pathological features of psoriatic arthritis (PsA). Given the potential physiological role for PPAR-gamma in PsA, we examined known coding polymorphisms in the PPAR-gamma gene in a Caucasian population.PsA was diagnosed as an inflammatory arthritis in patients with psoriasis, in the absence of other etiologies for inflammatory arthritis. Control subjects were ascertained from the same population and were all Caucasian. DNA samples were genotyped for 4 PPAR-gamma variants by time-of-flight mass spectrometry using the Sequenom platform. All 4 single-nucleotide polymorphisms (SNP) were previously-reported coding variations, 3 of which caused an amino acid change: Pro12Ala (rs1801282), Pro40Ala (rs1805192), and Pro115Gln (rs1800571); the fourth SNP, C161T (rs3856806), was synonymous. All primers were designed using Sequenom SpectroDesigner software, and scanned using a mass spectrometry workstation.Of the 4 SNP examined, Pro40Ala and Pro115Gln were found to be nonpolymorphic in our population. Minor allele frequency for patients with PsA and controls for Pro12Ala (G) were 9.0% vs 13.8% (p = 0.017) and for C161T (T) 10.7% vs 12.0% (p = 0.56), respectively. All genotypes satisfied Hardy-Weinberg equilibrium.An association between PsA and a known coding SNP of the PPAR-gamma gene was observed in our Caucasian population. Further studies are now warranted for validation of our findings in an independent cohort.

To examine the association of single nucleotide polymorphisms (SNP) in the NFKB1 gene, as well as 2 genes in the nuclear factor (NF)-kappaB functional complex (RelA and NFKBIA), in patients with psoriatic arthritis (PsA) from Newfoundland.Patients with PsA and controls were genotyped for one 4-base insertion/deletion and 5 SNP in NFKB1, 4 SNP in RelA, and 7 SNP in NFKBIA by time-of-flight mass spectrometry, using the Sequenom platform. Chi-square analysis was used to test the single locus associations between SNP in the NF-kappaB complex and PsA. Associations between multi-locus haplotypes and case or control status were tested using the software PHASE.Two hundred and twenty-four patients with PsA (52% male) and 88 ethnically matched controls (64% male) were genotyped. No association was noted with any of the SNP tested for the single locus associations in NFKB1, RelA, and NFKBIA or with multi-locus haplotypes. In particular, the allele frequency for the NFKB1 -94delATTG was 41.7% in cases and 41.6% in the controls (p = 0.97).No association between the NFKB1 -94 ins/delATTG promoter polymorphism or with other NF-kappaB complex SNP in patients with PsA from Newfoundland was observed.

Spondyloarthritis (SpA) represents a group of related arthritides characterized by their association with HLA-B27 and the development of sacroiliitis and enthesitis. Functional impairment, disability, and loss of quality of life may resemble that observed in rheumatoid arthritis. The SpA Research Consortium of Canada (SPARCC) is an informal association of rheumatologist members of the Canadian Rheumatology Association (CRA) with a special interest in therapeutics and outcomes research in SpA. Recent experience with anti-tumor necrosis factor-a (anti-TNF-a) directed therapies prompted a consensus-based evaluation of the evidence supporting their efficacy, safety, and appropriate use in SpA. We evaluated the clinical evidence in support of anti-TNF-a directed therapies in SpA. Medline was searched using appropriate keywords. Abstracts of the 1999-2002 annual meetings of the American College of Rheumatology and the European Congress of Rheumatology were extracted and admitted if sufficient detail was available to determine the level of evidence. Recommendations were based on randomized placebo-controlled trials (Level A evidence) and clinical studies without randomization (Level B evidence). Where the scientific literature was incomplete, recommendations reflected the consensus of SPARCC members (Level C evidence). Following development of an original draft document, consensus for revisions was achieved among members of SPARCC. The document was then posted on the CRA website prior to its final revision. The following recommendations have been endorsed by the Therapeutics Committee of the CRA: Infliximab and etanercept are indicated for reduction of signs and symptoms of moderate to severely active SpA in patients who have had an inadequate response to maximal doses ofor = 2 nonsteroidal antiinflammatory drugs (NSAID) over a 3-month period of observation; and either sulfasalazine or methotrexate is indicated in those with predominantly active peripheral arthritis. Current evidence supports their use as monotherapy (level of evidence A) for at least one year. NSAID and/or second line therapy with either sulfasalazine or methotrexate can be continued concomitantly. There is no evidence addressing potential advantages or disadvantages of combining methotrexate with anti-TNF therapy for SpA. Recommended doses for adults are: infliximab 5 mg/kg at 0, 2, and 6 weeks and every 8 weeks thereafter; etanercept 25 mg subcutaneously twice weekly. No therapy has been shown to slow progression of axial disease in SpA, and prognostic factors for determining response to therapy remain to be determined. It is the position of the CRA that all therapeutic options should be equally available according to the best judgments of the treating physician and the informed decision of the patient.

We investigated whether brief supportive-expressive group psychotherapy might reduce illness-induced interference with valued activities and interests (i.e., illness intrusiveness) among women with systemic lupus erythematosus (SLE) in relation to 3 life domains: (1) relationships and personal development (family relationships, other social relationships, self-expression), (2) intimacy (relationship with spouse, sex life), and/or (3) instrumental life (work, finances, active recreation).Women with SLE recruited from 9 rheumatology centers were randomly assigned to receive either usual care (n = 66) or a 12 week brief supportive-expressive group psychotherapy followed by 3 monthly booster sessions (n = 58). Standard instruments assessed disease activity and damage, illness intrusiveness, and psychological distress at 4 measurement occasions: (1) pretreatment, (2) posttreatment, (3) 6 month followup, and (4) 12 month followup.Analysis of covariance, controlling for disease activity and household income, indicated that women who received brief supportive-expressive group psychotherapy experienced significant reductions in illness intrusiveness for 2 of 3 domains: (1) relationships and personal development and (2) intimacy. Benefits were evident at 6 and 12 month followups.Brief supportive-expressive group psychotherapy facilitates adaptation to SLE by assisting women in reducing illness-induced disruptions into important domains of life experience.

To determine the longterm outcome in children with onset of lupus nephritis before 18 years of age.Sixty-seven patients with onset of lupus nephritis prior to age 18 were identified. The mean followup time was 11 years (range 5-19). The mean age at diagnosis was 13.2 years (range 4-17). The male:female ratio was 1:3.8. Renal biopsies were classified using the WHO classification. Fifteen patients had Class II, 8 patients Class III, 32 patients Class IV, and 11 patients Class V and one patient refused biopsy. The cohort consists of the 66 patients who had a renal biopsy. Five patients received cyclophosphamide (CYC) and 17 received azathioprine (AZA) as part of the initial treatment of Class IV nephritis. Eight additional patients received CYC because of a flare of disease while receiving AZA, and 8 other patients received AZA because of a flare of disease while taking prednisone therapy.Four patients died; 6 developed endstage renal disease (ESRD); all but one of the patients who died and/or had ESRD had WHO Class IV [diffuse proliferative glomerulonephritis (DPGN)]; only 2 Caucasians developed ESRD, although 16 out of 36 Caucasians had DPGN; serum creatinine at followup was normal in 84% of the survivors; presently 70% of the patients take less than 7.5 mg prednisone/day and 62% do not take cytotoxic drugs. No patient is currently treated with CYC. All 8 patients with Class III nephritis were taking medication at last followup.The longterm outcome in this group of children with lupus nephritis, in whom AZA was the most commonly used immunosuppressive agent, was excellent, with 94% patient survival at a mean followup of 11 years. Our results suggest that non-Caucasian patients with pediatric onset lupus nephritis may be at increased risk for renal failure compared to Caucasians.

To compare the extent and type of damage in patients with late onset and earlier onset systemic lupus erythematosus (SLE) using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI).A total of 86 SLE patients with disease onset after the age of 54 years were matched for center, sex, and ethnic origin with 155 SLE patients with disease onset before the age of 40 years. SDI scores were obtained at one year and 5 years after the diagnosis of SLE. Analysis was based on conditional logistic regression.SDI scores were higher in the late onset group than in younger patients at both one [mean 0.7 (range 0-3) vs 0.3 (range 0-3); p0.001] and 5 years [mean 1.6 (range 0-8) vs 0.9 (range 0-7); p0.001] after diagnosis. There was also a difference in the pattern of organ damage. While damage to the skin, kidneys, and central nervous system occurred with similar frequency, late onset disease was characterized by significantly more cardiovascular (OR 14.13, p0.001), ocular (OR 9.38, p = 0.001), and musculoskeletal (OR 2.68, p = 0.016) damage and malignancy (OR 7.04, p = 0.046).The occurrence of organ damage assessed by the SDI is greater in patients with late onset SLE than in younger patients and, by this criterion, lupus cannot be judged to be more benign in this age group. Also, the pattern of damage is different, but whether this reflects age per se or the effect of the disease in the elderly remains to be established.

Systemic lupus erythematosus is a genetically complex disease. Currently, the precise allelic polymorphisms associated with this condition remain largely unidentified. In part this reflects the fact that multiple genes, each having a relatively minor effect, act in concert to produce disease. Given this complexity, analysis of subclinical phenotypes may aid in the identification of susceptibility alleles. Here, we used flow cytometry to investigate whether some of the immune abnormalities that are seen in the peripheral blood lymphocyte population of lupus patients are seen in their first-degree relatives. Peripheral blood mononuclear cells were isolated from the subjects, stained with fluorochrome-conjugated monoclonal antibodies to identify various cellular subsets, and analyzed by flow cytometry. We found reduced proportions of natural killer (NK)T cells among 367 first-degree relatives of lupus patients as compared with 102 control individuals. There were also slightly increased proportions of memory B and T cells, suggesting increased chronic low-grade activation of the immune system in first-degree relatives. However, only the deficiency of NKT cells was associated with a positive anti-nuclear antibody test and clinical autoimmune disease in family members. There was a significant association between mean parental, sibling, and proband values for the proportion of NKT cells, suggesting that this is a heritable trait. The findings suggest that analysis of cellular phenotypes may enhance the ability to detect subclinical lupus and that genetically determined altered immunoregulation by NKT cells predisposes first-degree relatives of lupus patients to the development of autoimmunity.