Increased proportion of comorbidities but no deterioration of sexual quality of life during a 5-year follow-up in patients with axial spondyloarthritis in the biologic treatment era.

OBJECTIVE: To explore patient perception of sexual quality of life (SQOL), an important category of QOL, in male and female patients with axial SpA (axSpA) after a 5 year follow-up. METHODS: A broad spectrum of demographic, disease-related, treatment and SQOL data was collected at baseline and at the 5 year follow-up. SQOL was assessed by the SQOL-Female (SQOL-F) questionnaire. For statistical analysis, McNemar's tests, paired t-tests and multiple regression analyses were applied. RESULTS: A total of 245 axSpA patients (168 men and 77 women) from outpatient clinics were examined (mean age 46 years, mean disease duration 11.9 years at baseline). Compared with baseline, the patients had lower CRP, lower Maastricht Ankylosing Spondylitis Enthesitis Scores, lower BASFI scores, less use of smoking and significantly more patients were treated with biologic DMARDs at the 5 year follow-up. Patient perception of SQOL was basically unchanged at the 5 year follow-up despite a significantly increased proportion of comorbidities, including cardiovascular, endocrine and gastrointestinal disease. A decrease in SQOL after 5 years was observed only in patients exercising <1 h/week at baseline (P = 0.048) and in patients >65 years old. CONCLUSION: In our axSpA patients, no statistically significant changes in SQOL were observed over 5 years, despite a significant increase in comorbidities. Overall disease symptoms decreased, indicating better disease control. Increased use of biologic drugs at the 5 year follow-up may have contributed to this favourable outcome.

A questionnaire-based study on contraceptive practice in patients with rheumatic disease found no significant difference in age-matched healthy controls.

OBJECTIVE: Birth control is crucial in preventing unplanned pregnancy. The study analyzed contraceptive practice in women and men with rheumatic disease. METHODS: A questionnaire-based study investigated the actual contraceptive practices in patients of reproductive age from three European countries and compared them to age-matched healthy women and men. Associations between patient characteristics and contraception behavior were analyzed by association analysis. RESULTS: No significant difference in the frequency of contraception use was found in 133 rheumatic patients compared to 122 healthy controls. The main reason for not using contraception was lack of partner or the wish to become pregnant, whereas the current use of contraception was predominantly to limit family size in general or at this stage of life. Both patients and controls preferred barrier methods (48% and 45%, respectively) followed by hormonal contraceptives (31% and 38%, respectively). Characteristics associated with less use of contraception in patients were living single, having no children, and for being religious, whereas gender and education had no influence. Treatment with teratogenic drugs was no major patient concern, and 13 of 30 female patients using methotrexate, mycophenolate mofetil, or leflunomide did not practice birth control. CONCLUSION: Patients used contraception less frequently than healthy individuals, and the main reason for use was to limit family size. Contraception should be an integral part of counseling patients of fertile age, since the patient-preferred methods in case of active disease or therapy with teratogenic drugs were unreliable for the prevention of pregnancy.

Risk for adverse pregnancy outcome in axial spondyloarthritis and rheumatoid arthritis: disease activity matters.

OBJECTIVE: To analyse pregnancy outcome and delivery mode in patients with RA and axial spondyloarthritis (axSpA) in relation to disease activity and anti-rheumatic drugs. METHODS: Patients with RA and axSpA were compared with age-matched healthy controls (HCs) with respect to pregnancy outcome and delivery mode. Disease activity (DAS28, ASDAS, CRP) and medication use of patients was assessed once at each trimester. ORs with 95% CI were calculated with univariate and multivariate regression models. RESULTS: We analysed 244 pregnancies, of which 96 occurred in patients with RA, 78 in patients with axSpA and 70 in HCs. The adjusted analysis showed that pregnant women with RA and axSpA had a higher risk of pregnancy complications (gestational diabetes, preeclampsia, infection, preterm premature rupture of membranes), small for gestational age infants and preterm deliveries (all P < 0.05). Active disease was a predictor for preterm delivery in both RA [odds ratio (OR) = 3.9, 95% CI: 1.25, 12.15] and axSpA (OR = 13.8, 95% CI: 1.33, 143.94). Regarding delivery mode, most patients had vaginal deliveries. However, women with RA revealed an increased risk of caesarean section compared with HC (P < 0.05), which was not seen in patients with axSpA. CONCLUSION: Our findings show that disease activity of RA and axSpA during pregnancy influences pregnancy outcome. To allow for successful pregnancy a treatment strategy that targets inactive disease beyond conception should be followed.

Methotrexate Use and Monitoring in Patients with Psoriasis: A Consensus Report Based on a Danish Expert Meeting.

Methotrexate (MTX) has been used in the treatment of psoriasis and other dermatological diseases for more than 50 years. However, there is limited evidence regarding its effect, dose and monitoring, and a lack of consensus regarding how the drug should be used in daily practice. Although the use of MTX is governed by guidelines, such as the European S3-Guidelines and the National Institute for Health and Care Excellence (NICE) guideline, it is important to discuss and adjust these guidelines to national standards. An expert meeting was held in Denmark at the end of 2014, in order to reach consensus regarding the use of MTX in dermatological practice in Denmark. Participants included dermatologists, hepatologists, paediatricians, clinical biochemists and a rheumatologist. Topics discussed were: liver disease monitoring, teratogenic effects of MTX, risk of cancer, and use of MTX in children. We report here the conclusions of this expert meeting regarding use of MTX in dermatological practice.

The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation.

A European League Against Rheumatism (EULAR) task force was established to define points to consider on use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Based on a systematic literature review and pregnancy exposure data from several registries, statements on the compatibility of antirheumatic drugs during pregnancy and lactation were developed. The level of agreement among experts in regard to statements and propositions of use in clinical practice was established by Delphi voting. The task force defined 4 overarching principles and 11 points to consider for use of antirheumatic drugs during pregnancy and lactation. Compatibility with pregnancy and lactation was found for antimalarials, sulfasalazine, azathioprine, ciclosporin, tacrolimus, colchicine, intravenous immunoglobulin and glucocorticoids. Methotrexate, mycophenolate mofetil and cyclophosphamide require discontinuation before conception due to proven teratogenicity. Insufficient documentation in regard to fetal safety implies the discontinuation of leflunomide, tofacitinib as well as abatacept, rituximab, belimumab, tocilizumab, ustekinumab and anakinra before a planned pregnancy. Among biologics tumour necrosis factor inhibitors are best studied and appear reasonably safe with first and second trimester use. Restrictions in use apply for the few proven teratogenic drugs and the large proportion of medications for which insufficient safety data for the fetus/child are available. Effective drug treatment of active inflammatory rheumatic disease is possible with reasonable safety for the fetus/child during pregnancy and lactation. The dissemination of the data to health professionals and patients as well as their implementation into clinical practice may help to improve the management of pregnant and lactating patients with rheumatic disease.

Contraception and pregnancy counselling in rheumatoid arthritis.

PURPOSE OF REVIEW: The purpose of this study is to encourage discussion of reproduction issues in all patients of fertile age in order to prevent unplanned and ill-timed pregnancies in patients with rheumatoid arthritis (RA). RECENT FINDINGS: Counselling patients who desire children requires consideration of relevant reproductive health issues, including fertility, interaction of pregnancy and RA, and management during pregnancy and lactation. RA patients have no disease-related restrictions in regard to contraception, but need to be counselled on safe birth control particularly during treatment with potentially teratogenic drugs. In spite of mostly beneficial effects of pregnancy on RA, active disease and aggressive drug treatment can impair pregnancy outcomes. Options for drug therapy, though limited, may help to maintain low disease activity during pregnancy and lactation. SUMMARY: Careful preconception counselling and risk assessment is important in RA women, with a particular focus on preventing unplanned pregnancy by information on contraception. Antibody status and all medications need to be reviewed before pregnancy. Maintaining low disease activity before and during pregnancy is crucial for good outcomes. Preconceptional counselling shared with all health professionals engaged in the care of a patient helps to ensure healthy pregnancy outcomes for mother and child.

TNF-α inhibitors do not impair sperm quality in males with ankylosing spondylitis after short-term or long-term treatment.

OBJECTIVE: The aim of this study was to study the influence of active disease status and TNF-α antagonists on sperm quality in a group of AS patients. METHODS: Twenty-three active AS patients and 42 controls were recruited. Patients' sperm samples were analysed at baseline (previous to) and at 3-6 months after TNF-α therapy (adalimumab, infliximab, etanercept) administration. Baseline assessment was made for only 20 patients, 2 of them proving to have normal fertility, 2 having a pregnant stable partner and the third having a 9-month-old child. Six patients were retested after 12 months of biologic therapy. Each patient acted as his own comparator. Results were further compared with sperm samples from age-matched controls. Sperm analysis was performed according to the World Health Organization (WHO) 1999 guidelines. RESULTS: Patients' baseline assessment showed normozoospermia in 91% and oligozoospermia in 9% of patients. No significant differences in sperm quality were noticed at follow-up visits compared with baseline. Comparison to controls showed no statistically significant differences in semen quality, with some exceptions: the control group presented a higher percentage of non-progressive and immobile sperm cells and higher numbers of head and tail atypias. CONCLUSION: Sperm quality in patients with active AS and after receiving short- and long-term TNF-α blocker therapy is comparable to sperm quality in healthy controls. Our study confirms that the disease process of AS does not have a major impact on sperm quality and that treatment with anti-TNF has no negative impact on sperm quality even under long-term treatment.

Pathogenesis of pregnancy complications in systemic lupus erythematosus.

PURPOSE OF REVIEW: In spite of the advances made in the management of pregnancies in women with systemic lupus erythematosus (SLE), maternal complications and adverse fetal outcomes still exceed the rate of pregnancy complications in the general population. An intriguing question relates to the observation that pregnancy loss, intrauterine growth restriction (IUGR), preterm birth, and preeclampsia remain major complications in SLE pregnancies, not substantially altered by improved therapy and monitoring. RECENT FINDINGS: From the review of the recent literature on the pathogenesis of pregnancy loss, IUGR, preeclampsia, and prematurity, it appears that clinical or subclinical inflammation, presence of autoantibodies, hormonal dysfunction, and immune alterations of lupus contribute to pregnancy complications. Impairment of early placenta development leads to poor vascularization, resulting in placental ischemia and subsequent endothelial damage. Depending on the extent of the pathological process, pregnancy loss, IUGR, and preeclampsia can develop. SUMMARY: Early recognition of pregnancy complications is desirable in order to prevent their development or to prompt intervention that improves the outcomes. Several biomarkers have been investigated for their ability to predict complications at an early stage of pregnancy. However, up to date only lupus anticoagulant has emerged as a consistent predictor for adverse pregnancy outcomes.

Influence of pregnancy on the adipocytokine and peroxisome proliferator-activated receptor pathways in peripheral blood mononuclear cells from healthy donors and rheumatoid arthritis patients.

OBJECTIVE: To identify candidate genes that are regulated by human pregnancy and have the potential to modulate rheumatoid arthritis (RA) disease activity. METHODS: Peripheral blood mononuclear cells (PBMCs) from healthy pregnant volunteers were analyzed using Affymetrix GeneChips at 4 time points (during the first, second, and third trimesters and 6 weeks postpartum). Based on the GeneChip data, target genes were further analyzed via real-time quantitative polymerase chain reaction (qPCR) using PBMCs from healthy controls and RA patients. In order to determine the cellular source of the candidate gene messenger RNA (mRNA), monocytes and lymphocytes from healthy controls and RA patients were positively selected using magnetic beads, and their mRNA was analyzed by qPCR. RESULTS: One-way analysis of variance identified 1,286 mRNAs that were differentially expressed with regard to the 4 time points. The changes became more pronounced as pregnancy progressed, and they were reversed postpartum. A subsequent pathway analysis suggested a regulatory role of pregnancy on the adipocytokine pathway as well as on the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Of 19 preselected candidate genes, AKT3, SOCS3, FADS2, STAT1, and CD36 proved to be differentially regulated by pregnancy. In samples from RA patients, the differences were concordant with those in healthy controls but more pronounced. Both T lymphocytes and monocytes contributed to the regulated expression of these genes. CONCLUSION: Our findings indicate that normal human pregnancy leads to changes in the expression of several molecular pathways in PBMCs, which are reversed postpartum. Changes in RA patients, although concordant, exceed the levels observed in healthy controls. Genes of the adipocytokine and PPAR signaling pathways qualify as candidates for the modulation of RA disease activity during pregnancy.

Characteristics and Obstetric Outcomes in Women With Autoimmune Rheumatic Disease During the COVID-19 Pandemic in Qatar.

OBJECTIVE: Pregnant women with autoimmune rheumatic diseases are considered to have a high risk of obstetric complications with the emergence of the Coronavirus disease (COVID-19) pandemic. Therefore, we aimed to assess the impact of COVID-19 on this high-risk group. METHODS: This cross-sectional cohort study (March to December 2020) was conducted at the largest tertiary center in Qatar (Hamad Medical Corporation). Eighty consecutive patients following up at the center during pregnancy were surveyed through telephonic interviews. Data on COVID-19 and pregnancy outcomes were extracted from electronic hospital records. RESULTS: Eighty pregnant women with autoimmune rheumatic diseases were included. Among them, 17 (21.3%) (95% confidence interval [CI]: 12.9-31.8%) were diagnosed with COVID-19, five were hospitalized, and only one required intensive care unit admission. The proportion of adverse obstetric outcomes in the cohort was 29.5% (n = 23; 95% CI: 19.7-40.9%). Prematurity (n = 14; 19.4%) and caesarean section (n = 30; 41.1%) were the most prevalent adverse events. There was no statistical difference in adverse pregnancy outcomes between women with and without COVID-19. CONCLUSION: COVID-19 did not affect pregnancy outcomes in women with autoimmune rheumatic diseases.

Treatment with biologics of pregnant patients with rheumatic diseases.

OBJECTIVE: Due to limited human pregnancy experience safety issues in regard to children exposed antenatally to biological drugs are still under debate. A survey of new published experience on biological agents during pregnancy is necessary to assist clinicians with adequate counseling and management of patients who desire children. RECENT FINDINGS: No controlled study has been published on use of TNFα inhibitors, rituximab, abatacept, tocilizumab or anakinra in pregnancy during the years 2009-2010. New case reports confirm that all monoclonal antibodies expose the child to the full adult dose when administered in late pregnancy with a risk for adverse effects in the newborn and perinatally. Data from a drug registry show that preconceptional and early first-trimester use of rituximab appears to confer no serious side effect to the child. Case reports on abatacept, tocilizumab or anakinra in pregnancy are not conclusive. SUMMARY: Differences in molecular structure of TNFα inhibitors may turn out to favor the use of agents that are not complete monoclonal antibodies in women who consider pregnancy. The very limited experience with abatacept, tocilizumab or anakinra in pregnancy allows no statement as to their compatibility with pregnancy. At present use of biological agents throughout pregnancy cannot be recommended.

Pregnancy and reproduction in autoimmune rheumatic diseases.

Despite evidence for the important role of oestrogens in the aetiology and pathophysiology of chronic immune/inflammatory diseases, the previous view of an unequivocal beneficial effect of oestrogens on RA compared with a detrimental effect on SLE has to be reconsidered. Likewise, the long-held belief that RA remits in the majority of pregnant patients has been challenged, and shows that only half of the patients experience significant improvement when objective disease activity measurements are applied. Pregnancies in patients with SLE are mostly successful when well planned and monitored interdisciplinarily, whereas a small proportion of women with APS still have adverse pregnancy outcomes in spite of the standard treatment. New prospective studies indicate better outcomes for pregnancies in women with rare diseases such as SSc and vasculitis. Fertility problems are not uncommon in patients with rheumatic disease and need to be considered in both genders. Necessary therapy, shortly before or during the pregnancy, demands taking into account the health of both mother and fetus. Long-term effects of drugs on offspring exposed in utero or during lactation is a new area under study as well as late effects of maternal rheumatic disease on children.

Biologics and small molecules in the management of psoriatic arthritis: Reproduction related issues in female and male patients.

STRACTBackground: Psoriatic arthritis (PsA) is the musculoskeletal manifestation of psoriatic disease, an inflammatory systemic disease with a high incidence in the reproductive years. Biologic and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) as well as 'small molecules', are increasingly used to treat subtypes of PsA. Safety concerns exist in the field of fertility for PsA patients since the literature shows discordant results toward the influence of anti-psoriatic drugs.Areas covered: This comprehensive review critically reviews the available data on the safety of biologics and small molecules in PsA including pregnancy and lactation and men who want to father a child. TNF inhibitors (TNFi) are best studied in relation to reproduction. For other biologics and small molecules, no prospective, controlled studies are available.Expert opinion: No contraindications appear for TNFi in pregnancy, lactation, and paternal exposure. For biologics other than TNFi and small molecules, prospective controlled studies on outcomes after exposure in early and late pregnancy are urgently needed. Potential effects of all biologics on immune function, infection rates, and vaccine responses in prenatally exposed children need to be expanded. Until more data become available, small molecules should be avoided during pregnancy and breastfeeding. More reproduction-related data are expected from various national and international registries in the future.

Effects of TNF antagonists on sperm characteristics in patients with spondyloarthritis.

OBJECTIVE: To study the influence of tumour necrosis factor (TNF) antagonists on spermatogenesis in a cohort of patients with spondyloarthritis (SpA). PATIENTS AND METHODS: Semen samples of 26 patients with SpA were analysed according to WHO 1999 guidelines with and without TNF blocking agents (infliximab, etanercept or adalimumab). RESULTS: were compared with semen samples of 102 healthy volunteers. Results Sperm abnormalities were found in 10/11 patients without anti-TNF therapy. The sperm of these 11 patients had significantly poorer motility (p=0.001) and vitality (p=0.001) than found in 15 patients tested during longstanding anti-TNF therapy, but sperm concentration and morphology were similar in the two groups. There was no significant difference of sperm quality between healthy controls and anti-TNF treated patients with SpA. Notably, sperm abnormalities were also found in 102 healthy controls. CONCLUSION: Sperm abnormalities are a common finding in healthy men, they are more pronounced in patients with active SpA. The sperm quality of patients with SpA with inactive disease receiving long-term TNF inhibition is comparable to that in healthy controls. The data support continuation of anti-TNF treatment when fatherhood is planned.

Sexual Quality of Life in Patients with Axial Spondyloarthritis in the Biologic Treatment Era.

OBJECTIVE: To examine the relationship between demographics, disease-related variables, treatment, and sexual quality of life (SQOL) in men and women with axial spondyloarthritis (axSpA). METHODS: AxSpA patients were consecutively recruited from 2 rheumatology outpatient clinics in southern Norway. A broad spectrum of demographics, disease, treatment, and QOL data were systematically collected. SQOL was assessed using the SQOL-Female (SQOL-F) questionnaire (score range 18-108). Appropriate statistical tests were applied for group comparison, and the association between independent variables and SQOL-F was examined using multiple linear regression analysis. RESULTS: A total of 360 (240 men, 120 women) axSpA patients with mean age 45.5 years and disease duration 13.9 years were included. Seventy-eight percent were married/cohabiting, 26.7% were current smokers, 71.0% were employed, 86.0% performed > 1-h exercise per week, and 88.0% were HLA-B27-positive. Mean (SD) values for disease measures were C-reactive protein (CRP) 8.5 (12.1) mg/l, Bath Ankylosing Spondylitis Disease Activity Index 3.1 (2.1), Bath Ankylosing Spondylitis Global Score (BAS-G) 3.8 (2.5), Bath Ankylosing Spondylitis Functional Index 2.7 (2.2), and Health Assessment Questionnaire 0.6 (0.5). The proportion of patients using nonsteroidal antiinflammatory drugs was 44.0%, synthetic disease-modifying antirheumatic drugs (DMARD) 5.0%, and biologic DMARD 24.0%. Mean (SD) total sum score for SQOL was 76.6 (11.3). In multivariate analysis, female sex, increased body mass index, measures reflecting disease activity (BAS-G and CRP), and current biologic treatment were independently associated with a lower SQOL. CONCLUSION: Our data suggest that inflammation in patients with axSpA even in the biologic treatment era reduces SQOL.

Pregnancy Outcomes in Couples with Males Exposed to Longterm Anti-tumor Necrosis Factor-α Inhibitor Therapies: A Prospective Study.

OBJECTIVE: To examine the pregnancy achievement and outcomes in couples in which men with spondyloarthritis (SpA) were exposed to tumor necrosis factor inhibitors (TNFi). METHODS: Information about pregnancies involving fathers with SpA was prospectively collected by 6 Romanian rheumatology centers. RESULTS: Twenty-seven patients achieved 33 pregnancies and fathered 30 healthy children. Three elective abortions (personal reasons) and no spontaneous abortions, preeclampsia/eclampsia, stillbirths, congenital malformations, or pathologies in the children were recorded. Five patients showed normospermia before and after longterm TNFi treatment. CONCLUSION: Pregnancy and child outcomes in male patients with SpA exposed to longterm TNFi therapy were reassuring.

From mother to baby: antenatal exposure to monoclonal antibody biologics.

INTRODUCTION: More women with autoimmune and inflammatory conditions are being treated with monoclonal antibody biologics (mAbs) during their pregnancy, to maintain clinical remission. The use of anti-tumor necrosis factor alpha agents in pregnancy appears to be safe but less is known regarding other mAbs, such as anti-integrins and anti-cytokine agents. There are currently no comprehensive guidelines on how to manage the exposed infants. Areas covered: We review recent literature to assess the impact of mAbs on birth and early infant outcomes, including what is currently known about maternal and infant drug levels at birth and drug clearance in the infant. We describe the potential risks of infections and reported hematological and immunological effects of antenatal mAbs exposure on the infant and provide guidance on the management of the exposed infant. Expert opinion: Exposed infants should be monitored closely. Certain mAb exposures require specific testing and management. Safety monitoring should be done in a multidisciplinary approach and should include pediatric care providers. The current clinical experience with anti-tumor necrosis factor agents in pregnancy cannot be extrapolated to other mAbs. Long-term observational studies and a multicenter international registry are needed to better appreciate the impact of exposure, especially to newer mAbs.