Pregnancy outcomes in Australian patients with systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) affects women, with the onset of disease typically around the childbearing years. AIMS: This study examines the frequency and risk factors for adverse pregnancy outcomes (APOs) in an Australian cohort, and any disease flares during pregnancy and post partum. METHODS: Female patients with SLE enrolled in the Australian Lupus Registry and Biobank (ALRB) between January 2007 and June 2019 were studied. Self-reported pregnancy history, including adverse foetal or maternal outcomes, was collected at the time of enrolment and updated as appropriate. Baseline demographics, clinical parameters, medication exposure and disease activity were collected. Factors associated with APO were examined using univariate and multivariate logistic regression analyses. RESULTS: Pregnancy history was available in 278 patients; 30% were nulliparous. Most pregnancies occurred before the diagnosis of SLE. Patients who had pregnancies after SLE diagnosis had an earlier age of diagnosis, and had fewer pregnancies. The APO rate was 44.3% in the overall cohort, with most presenting as prematurity with or without foetal growth restriction. Women with APO were also diagnosed with SLE at a younger age and had a higher prevalence of anti-cardiolipin antibodies and hypocomplementemia. Early age of SLE diagnosis was a significant independent risk factor for APO. No increase in disease flare was observed in those who experienced APO during the observation period of ALRB. CONCLUSION: This study shows a considerable incidence of APO in patients with SLE, emphasising the need for pre-pregnancy counselling and collaboration between maternal-foetal medicine specialists and rheumatologists, especially for women diagnosed with SLE at a younger age.

Effects of cyclophosphamide administration on ovarian dysfunction in pediatric patients with connective tissue diseases: A systematic scoping review.

OBJECTIVE: This systematic scoping review assess the effect of cyclophosphamide (CY) administration during childhood on ovarian function in patients with juvenile-onset connective tissue diseases. METHODS: A MEDLINE database search was conducted using terms related to CY, juvenile-onset connective tissue diseases, and ovarian function. Studies were included if they met specific criteria. RESULTS: The search, conducted on 28 November 2023, yielded 3328 references. After a two-stage screening process, six observational studies on systemic lupus erythematosus patients were included. All studies had a high risk of confounding bias, as none adjusted for confounding variables. Two studies assessing clinical ovarian dysfunction found no clear difference between CY and non-CY groups. However, statistical differences were observed in hormonal profiles. Decreased ovarian reserve was more frequent in CY-exposed patients. Two studies showed significantly higher follicle-stimulating hormone (FSH) levels in the CY group, while one showed a trend towards higher FSH levels without statistical significance. CONCLUSION: This review suggested that CY use in childhood may not conclusively have clinically significant effects on ovarian function. Further investigation needed on CY's effect on hormonal levels, fertility, and pregnancy outcomes.

Physician approval for pregnancy in patients with systemic lupus erythematosus showing only serological activity: A vignette survey study.

OBJECTIVE: The European League Against Rheumatism recommends that the disease activity of systemic lupus erythematosus should be stable before pregnancy because complications and disease flares increase if pregnancy occurs while disease activity is high. However, some patients have ongoing serological activity even after treatment. Herein, we investigated how physicians decide on the acceptability of pregnancy in patients showing only serological activity. METHODS: A questionnaire was administered from December 2020 to January 2021. It included the characteristics of physicians, facilities, and the allowance for pregnancies of patients using vignette scenarios. RESULTS: The questionnaire was distributed to 4946 physicians, and 9.4% responded. The median age of respondents was 46 years, and 85% were rheumatologists. Pregnancy allowance was significantly affected by the duration of the stable period and status of serological activity [duration: proportion difference 11.8 percentage points (p.p.), P < .001; mild activity: proportion difference -25.8 p.p., P < .001; high activity: proportion difference -65.6 p.p., P < .001]. For patients with high-level serological activity, 20.5% of physicians allowed pregnancy if there were no clinical symptoms for 6 months. CONCLUSIONS: Serological activity had a significant effect on the acceptability of pregnancy. However, some physicians allowed patients with serological activity alone to become pregnant. Further observational studies are required to clarify such prognoses.

Serum anti-Müllerian hormone levels in women with rheumatoid arthritis during tumor necrosis factor-α inhibitor treatment: Exploratory research.

BACKGROUND: We evaluated serum anti-Müllerian hormone in women with rheumatoid arthritis newly introduced to tumor necrosis factor-α inhibitor treatment for 54 weeks to investigate the treatment's effect on ovarian reserve. METHODS: A total of 12 premenopausal women with rheumatoid arthritis aged 20-50 years were recruited at our division, who had been newly treated with tumor necrosis factor-α inhibitor (infliximab or etanercept) from 1 April 2008 to 31 March 2014. Serial serum anti-Müllerian hormone levels and disease activity scores (DAS28-CRP) were examined at defined periods: start of treatment and 14, 30, and 54 weeks after start of treatment. RESULTS: DAS28-CRP scores in 12 women were significantly decreased from a mean of 4.6 (±SD: 0.4) to 2.3 (±0.4) after 54 weeks of treatment (p < 0.001). Serum anti-Müllerian hormone levels and its z scores did not change significantly. CONCLUSION: Treatment with a tumor necrosis factor-α inhibitor did not affect serum anti-Müllerian hormone levels in 12 women with rheumatoid arthritis during 54-week treatment.

Polymyositis-Dermatomyositis and Interstitial Lung Disease in Pregnant Woman Successfully Treated with Cyclosporine and Tapered Steroid Therapy.

Polymyositis-dermatomyositis is extremely rare during pregnancy, and immunosuppressive therapy should be administered after carefully considering the effects on both the mother and fetus. Several reports have associated the disease activity with fetal prognosis, higher rates of eclampsia, preterm births, and fetal deaths. We report our experience with a patient who was diagnosed with polymyositis-dermatomyositis complicated by interstitial lung disease during pregnancy and was treated with a combination-immunosuppressant regimen. To the best of our knowledge, this is the first case wherein cyclosporine was used concomitantly with a steroid for the treatment of polymyositis diagnosed during pregnancy, with successful outcome of childbirth without any complications.

Clinical Characteristics of Rheumatoid Arthritis Patients Achieving Functional Remission with Six Months of Biological DMARDs Treatment.

Objective Although previous studies have reported the prognostic factors for functional remission, no reports have cited the predictive factors. Our aim was to study the predictive factors for functional remission, which is a treatment goal in rheumatoid arthritis (RA), after receiving biological disease-modifying antirheumatic drugs (bDMARDs) treatment for six months. Methods The study consisted of 333 RA patients treated with bDMARDs for six months. The following patient characteristics were investigated: age, gender, disease duration, type of bDMARDs, baseline steroid and methotrexate dosage, and levels of serum rheumatoid factor, matrix metalloprotease, anti-cyclic citrullinated peptides antibody, tumor necrosis factor-α, and interleukin-6. In our evaluation, we used the Simplified Disease Activity Index (SDAI) for RA disease activity, health assessment questionnaire disability index (HAQ-DI) for activity of daily living, Short Form (SF)-36 for quality of life, and Hamilton Depression Rating Scale (HAM-D) or Self-rating Depression Scale (SDS) to determine the patients' depression status. The subjects were divided into two groups: patients with HAQ-DI≤0.5 and HAQ-DI>0.5 at 6 months. Results A univariate analysis comparing a group of RA patients without functional remission (n=68) showed that the patients with functional remission (n=164) had the following in common compared with those without remission: younger age, shorter disease duration, lower baseline steroid dosage, lower SDAI, lower HAQ-DI, higher SF-36, and lower HAM-D. Only lower HAQ-DI scores and "mental health" score on the SF-36 were detected using a logistic regression analysis. Conclusion These findings suggested that RA patients with lower HAQ-DI and lower depression scores at baseline were more likely to achieve functional remission using bDMARDs treatment than those without these variables.

Comparative Study of Infliximab Therapy and Methotrexate Monotherapy to Improve the Clinical Effect in Rheumatoid Arthritis Patients.

Objective We examined whether infliximab (IFX) therapy was more effective than methotrexate (MTX) monotherapy to achieve an improvement in depressive states in Rheumatoid Arthritis (RA) patients. Methods We examined 152 RA patients (72 IFX patients and 80 MTX patients). We conducted an open-label cohort study to evaluate the disease activity of RA (Simplified Disease Activity Index; SDAI), depressive states (Hamilton Rating Scale for Depression; HAM-D), Activity of Daily Living (ADL) (modified Health Assessment Questionnaire; mHAQ) and Quality of Life (QOL) [Short Form (SF)-36] in patients before and 6 months after receiving therapy. The HAM-D, SDAI, mHAQ and SF-36 scores after 6 months of therapy were measured as the outcomes. Results We analyzed 60 IFX patients and 53 MTX patients. The HAM-D scores significantly improved in both groups (p<0.001), but there was no significant difference in the effectiveness between the IFX and MTX therapies (p=0.792). The SDAI scores significantly improved in both groups after therapy (p<0.001), and IFX therapy was more effective than MTX therapy (p=0.004). The mHAQ and HAM-D scores also improved significantly in both groups after therapy (p<0.001), but no significant difference in the effectiveness between the IFX and MTX therapies was observed (p=0.272, 0.792). The scores of all 8 items of the SF-36 improved in both groups after therapy, but IFX therapy was more effective than MTX therapy in only 4 of the 8 items (p<0.05). Conclusion Both IFX and MTX therapy improved the clinical efficacy, ADL, QOL and depressive states. However, no significant differences regarding an improvement in the depressive states and ADL were observed between IFX therapy and MTX monotherapy.

A case of Degos disease: demonstration of C5b-9-mediated vascular injury.

A 68-year-old Japanese male presented with atrophic erythematous white lesions with peripheral dark reddish rims on his back. Multiple ulcers were detected from his stomach to his large intestine using endoscopy. Although the patient was given high doses of a steroid, aspirin, dipyridamole, and intravenous immunoglobulin therapy, he died of gastrointestinal hemorrhage, perforation and septic shock. An autopsy examination revealed pauci-inflammatory thrombotic microangiopathy with endothelial cell injury, fibrous occlusive arteriopathy, and vascular C5b-9 deposition in the wall of the gastrointestinal tract from the esophagus to the large intestine as well as in the dermis of the skin.

Serum anticyclic citrullinated protein antibody titers are correlated with the response to biological agents in patients with rheumatoid arthritis.

Anticyclic citrullinated protein antibody (ACPA) is known as an important indicator for diagnosis of rheumatoid arthritis (RA). Our aim was to examine the relationship between the serum ACPA titer at baseline and responsiveness to biological agents (antagonists of either tumor necrosis factor or interleukin 6) in patients with RA. ACPA was measured using second-generation chemiluminescent enzyme immunoassay. Disease activity was assessed using disease activity scores 28. Fifty-seven RA patients with biological agents were enrolled, and the median ACPA titer at baseline was 110.0 U/mL. The median ACPA titer was 23.3 U/mL and 183.0 U/mL in the good and moderate response groups, respectively, which were significantly lower than in the no response group (404.0 U/mL). In addition, 69.2% and 26.9% of patients with low (<100 U/mL) and moderate (100-499 U/mL) basal ACPA titers showed a moderate to good response. Of the patients with higher (≥500 U/mL) basal ACPA titers, only 14.0% and 42.5% showed a good or moderate response, respectively. The remission rate was 77.8% in the ACPA-negative, which was significantly higher than the rate of 25% in the ACPA-positive patients. The results suggest that the ACPA titers are correlated with the efficacy of the biological agents used in patients with RA.

Serum macrophage migration inhibitory factor levels are correlated with response to tocilizumab therapy in patients with rheumatoid arthritis.

To examine the relationship between serum cytokine levels and response to tocilizumab in patients with RA. The disease status of 21 RA patients was assessed at baseline and after 12 weeks of tocilizumab treatment, using the clinical disease activity index (CDAI). Clinical response to tocilizumab was defined as an improvement of >50% from the baseline CDAI. Serum cytokine levels were quantified using double-ligand ELISA for TNF-α, IL-6, CCL2, CCL3, CXCL8, CXCL10, CX3CL1, and macrophage migration inhibitory factor (MIF). After 12 weeks of tocilizumab treatment, there was a significant overall reduction in RA disease activity (CDAI), from 22.4 ± 11.3 to 9.2 ± 6.6 (p < 0.0001), across the entire patient group. After 12 weeks of tocilizumab treatment, 14 patients achieved a >50% improvement (the responder group), but there were no significant responses in the other 7 patients (the non-responder group). The erythrocyte sedimentation rate levels, the positive % of anti-cyclic citrullinated protein antibody and patients (%) receiving methotrexate in combination with tocilizumab were significantly higher in the responder group than in the non-responder group. Although serum baseline levels of CCL2 and CXCL8 were higher in the responder group than in the non-responder group, there were no significant changes in these chemokine levels after treatment. The serum MIF levels, but not the levels of other cytokines, in the responder group were significantly decreased after tocilizumab treatment. Our results suggest that tocilizumab differentially regulates serum cytokine profiles in patients with RA, and MIF regulation in patients with active RA may be sensitive to anti-IL-6 therapy.

Effect of TNF antagonists on the productivity of daily work of patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a significant cause of work disability and job loss. The resulting economic burden experienced by patients has received considerable research attention. This research assesses the effect of tumor necrosis factor (TNF) antagonists (infliximab, etanercept) on the ability of RA patients living in Japan to work and participate in society. A total of 42 patients with active RA were enrolled and given biological therapy for 12 months (mo). Of these patients, 14 were employed full-time, 6 were employed part-time, and 22 were not employed. Twenty-six patients were given infliximab, and sixteen were given etanercept. The amount of domestic labor performed before the biologics served as a baseline and was assigned a value of 0%. After treatment with biologics, the productivity was evaluated using the visual analog scale (VAS; -100 to +100 mm). The administration of TNF antagonists to RA patients who exhibited an insufficient response to medical treatment significantly improved the Disease Activity Score 28 (DAS 28) after both 6 mo and 12 mo (P < 0.0001). A significant correlation was found between the improvement in their DAS 28 and improvements in their work situation (Productivity VAS) (P < 0.05). Of particular interest is the significant correlation between the values of baseline mHAQ and the percent changes of Productivity VAS that was observed after 6 mo and 12 mo (P < 0.05). Our findings indicate that medical treatment of RA with TNF antagonists improves the patients' ability to perform their jobs and housekeeping. Because loss of productivity is an important contributor to the indirect costs of RA, our findings are relevant for the pharmacoeconomic assessment of treatments.

Early plasmapheresis followed by high-dose γ-globulin treatment saved a severely Rho-incompatible pregnancy.

An alloimmunized pregnancy induces anemia in the fetus and can ultimately lead to fetal hydrops and intrauterine fetal death. A woman with a severe Rho-incompatible pregnancy had experienced frequent pregnancies with fetomaternal transfusion without receiving RhIg and had high anti-D antibody titers present from early pregnancy. We succeeded in long-term inhibition of antibody production using plasmapheresis followed by high-dose γ-globulin treatment in early pregnancy.

Relationship of Th1/Th2 cell balance with the immune response to influenza vaccine during pregnancy.

To determine the optimal timing for influenza vaccination in pregnant women, we measured alterations in the types 1 and 2 T helper cell (Th1/Th2) balance during pregnancy, monitored specific immunity to inoculated antigens after vaccination with inactivated influenza vaccine, evaluated the relevance of the Th1/Th2 ratio and immune responses to the vaccination, monitored the maintenance of high antibody titers until delivery and measured the transplacental antibody transfer rate. No significant alterations of the Th1/Th2 balance were noted in the 65% of pregnant women among whom the Th1/Th2 ratio was lower than 9.9% in the first trimester. In those groups with a ratio higher than 10% in the first trimester, there was a tendency for the ratio to decrease as gestation advanced. The efficiency of immunization was not influenced by the Th1/Th2 status or by the stage of gestation. The antibody titer decreased steadily with time from 1 month after vaccination to the time of delivery. Conversely, the transfer rate of antibodies from maternal to fetal blood at the time of delivery increased with the duration of gestation after vaccination. Nevertheless, the antibody titers in both maternal and fetal blood were sufficient to afford protection against infection. Thus, efficient influenza vaccination can be undertaken at any stage of pregnancy.