Background: The duration of time required for conception, known as Time to Pregnancy (TTP), is prolonged in women diagnosed with rheumatoid arthritis (RA). High rates of infertility, defined as the inability to conceive within a one-year timeframe, were observed in female patients diagnosed with RA. RA-related factors that influence TTP were previously studied in the Pregnancy-induced Amelioration of RA (PARA) cohort. Those factors include high disease activity, daily nonsteroidal anti-inflammatory drug (NSAID) use and daily prednisone intake exceeding 7.5 mg. In the Preconception Counseling in Active RA (PreCARA) study, women who wish to conceive were followed in a clinical pathway with counseling and treatment according to a treat-to-target (T2T) approach, aimed at remission, but avoiding the use of NSAIDs and high those prednisone. To achieve this, sulfasalazine and hydroxychloroquine were prescribed and if needed, TNF-inhibitors (TNFi) or low dose prednisone was added. Objectives: To investigate whether the implementation of a T2T strategy, including TNFi use, in women with rheumatoid arthritis (RA) in the PreCARA cohort is associated with a shorter TTP compared to the historical PARA cohort. Methods: In both cohorts, women were included before conception or during the first trimester of pregnancy. TTP was computed by measuring the interval between unprotected sexual intercourse and the onset of the last menstrual period. A comparative analysis of fertility outcomes between the PreCARA and PARA cohorts was conducted. Results: 215 patients were included in the PreCARA study, while the former PARA study included 245 patients. The median disease activity was DAS28CRP(3) 2.33 in PreCARA patients during the preconception period, compared to DAS28 of 3.84 in PARA patients. In the PreCARA study, 3% of the patients did not take any medication during the preconception period, compared to 36% in the PARA study. During the preconception period, NSAIDs use was observed in 13% of PreCARA patients and 24% of PARA patients. In the PreCARA study, 23 of 96 (23%) patients that used prednisone, took daily doses over 7.5 mg, compared to 41 out of 85 (48%) PARA patients. In the PreCARA study, 53% of the patients used TNFi during the preconception period. In the PARA study, only 9 patients (3%) used TNFi. In the PreCARA study, the median TTP is 84 days in patients who got pregnant, in contrast to 196 days observed in the PARA study (Figure 1). TTP exceeded 12 months in 23% of PreCARA patients compared to 42% in the PARA patients. Conclusion: TTP was shorter in PreCARA patients compared to PARA patients. This indicates that fertility is increased in women with RA when treated according to a T2T strategy, whilst avoiding NSAIDs and high doses prednisone. REFERENCES: NIL. Acknowledgements: We thank all participants of the PreCARA and PARA study. Disclosure of Interests: Cornelia H. Quaak: None declared, Esther Röder: None declared, Hetty Wintjes: None declared, Anneke J. van Steensel - Boon: None declared, Annemarie G.M.G.J. Mulders: None declared, Laura JC Kranenburg - van Koppen: None declared, Radboud J.E.M. Dolhain UCB, PreCARA study: unrestricted grant from UCB.Figure 1Time to pregnancy in the PARA (no-T2T) and PreCARA (T2T) cohort; survival curve for being pregnant within 5 years.

ObjectivesInflammatory arthritis (IA) has been associated with various problems related to male sexual and reproductive health (SRH). However, addressing these issues in the clinic remains a challenge. In this study, we aimed to describe the viewpoints of rheumatologists and male patients with IA regarding the aspects that influence their communication about SRH.MethodsRheumatologists and adult men with IA were invited to participate. This study uses Q-methodology, a mixed methods approach to systematically study subjectivity. Participants ranked 32 aspects according to their degree of influence (least-most influence) in addressing SRH and were then interviewed. Factor analysis was used to identify common patterns in the rankings. These patterns were interpreted as the different viewpoints of rheumatologists and male patients, supported by the qualitative data from the interviews. To obtain more generalizable results, the study was conducted in two countries with different socio-cultural backgrounds and healthcare systems, The Netherlands and Mexico.Results30 rheumatologists and 30 men with IA were included in each country. The analysis revealed three viewpoints in each group. Rheumatologists are more likely to be influenced by aspects such as the patient's desire to become a father or the patients' (young) age, but patients by a much more diverse pool of aspects, such as potential side effects of medication on their sexual function.ConclusionsThis study identified different viewpoints on the aspects that influence discussing SRH between rheumatologists and male patients, and important differences in viewpoints between both groups. Further research is needed to reach consensus on how and when rheumatologists and male patients should discuss SRH.

Objectives While protection against pertussis following maternal tetanus-diphtheria-and-acellular-pertussis (Tdap) vaccination was demonstrated in healthy term-born infants, no evidence is available on Tdap vaccination in combination with immune-modulating therapy during pregnancy. In this pilot study, we explored whether treatment with tumour necrosis factor alpha inhibitors (TNFis) in pregnant patients with rheumatic disease interferes with Tdap vaccine responses and affects maternal anti-pertussis IgG antibody levels in newborns. Methods Patients were included by a rheumatologist during pregnancy in case they received maternal Tdap vaccination in the late-second or early-third trimester of pregnancy. Blood samples were obtained from mothers during the first pregnancy trimester, 3 months after delivery and from the umbilical cord. IgG antibody levels against Tdap-included antigens were measured using a bead-based multiplex immunoassay. Findings on patients exposed to TNFis were compared with those from TNFi-unexposed patients and with data from a historical comparator study among healthy Tdap vaccinated mother–infant pairs (n=53). Results 66 patients (46 exposed and 20 unexposed to TNFIs) were enrolled. No major differences in IgG antibody levels were observed between TNFi-exposed and unexposed mothers before maternal Tdap vaccination and 3 months after delivery. In cord sera, however, antibody levels against pertussis toxin were significantly lower after TNFi-treatment (35.94 IU/mL, 95% CI 20.68 to 62.45) compared with no TNFi-treatment of mothers with rheumatic disease (94.61 IU/mL, 95% CI 48.89 to 183.07) and lower compared with a cohort of healthy mothers (125.12 IU/mL, 95% CI 90.75 to 172.50). We observed similar differences for filamentous haemagglutinin, pertactin, tetanus toxoid and diphtheria toxoid. Conclusion These preliminary data indicate no major differences in IgG antibody levels on maternal Tdap vaccination in pregnant women with or without immune-modulating treatment, although our findings suggest that TNFis during pregnancy induce lower maternal anti-pertussis-specific protective antibody levels in newborns.

BackgroundMethotrexate (MTX) is one of the most frequently prescribed medications for the treatment of several immune-mediated diseases (IMD). MTX has well-established safety and efficacy profiles. Nonetheless, the available scientific evidence to support the decision whether men with an active desire to become a father should be treated with MTX is dubious (1). This knowledge gap is characterized by a lack of prospective studies evaluating the semen parameters before and after exposure to MTX (2).ObjectivesOur objective is to compare the semen parameters (sperm concentration, volume and progressive motility) between men diagnosed with IMD (pre and post exposure to MTX) and healthy controls.MethodsThis is a prospective cohort study. Men diagnosed with an IMD (RA, SpA, psoriasis) who were older than 18 years and received a medical indication to start therapy with MTX were invited to participate (naïve cases). These men were instructed to produce 2 semen samples (a pre-exposure sample before initiating MTX therapy and a post-exposure sample 12 weeks after initiating MTX therapy). Healthy men who were over 18 years old were invited to participate as healthy controls. Furthermore, to evaluate the semen parameters of men chronically exposed to MTX, men diagnosed with an IMD who had been exposed to MTX (≥15 mg/week) for at least 1 year were also invited to participate (chronic cases). These men produced one semen sample (post-exposure). All participants were proven fertile (fathered a child or their partner reported a positive pregnancy test). Continuous variables were compared using a paired t-test or a one-way analysis of variance.ResultsIn total 18 naïve cases, 25 healthy controls and 5 chronic cases were included. Their demographic characteristics and the results of the conventional semen analysis are presented per group in Table 1. Compared to the semen parameters (sperm concentration, volume and progressive motility) from healthy controls, pre-exposure and post-exposure semen parameters from naïve cases were not statistically significant different (see Figure 1). The semen parameters of chronic cases were also not statistically significant different compared to pre-exposure samples from naïve cases and to healthy controls. Oligospermia (sperm concentration <15 10^6/mL) was identified in two samples from a naïve case (pre and post-exposure to MTX) and no cases of azoospermia were identified.Table 1.Demographic, clinical characteristics and semen parametersMTX naïveControlsMTX chronicp valuePre-exposurePost-exposureTotal, n18255Age, mean (95% CI)36.52 (33.65-39.39)34.56(32.75-36.36)36.80(31.95 – 41.64)MTX dose mg/week, mean (95% CI)-16.52(14.54 – 18.49)-18.00(14.59 – 21.40)Sperm concentration, mean × 10^6/ mL (95% CI)84.27(44.27-123.83)64.31(42.55 – 86.35)92.56(60.45 –124.66)44.60(25.11 – 64.08)p=0.358*p=0.280**Progressive motility*, % (95% CI)63.20(55.44-70.95)60.11(49.56-70.67)56.95(51.05-62.85)50.40(34.82 – 65.97)p=0.562*p=0.456**Semen volume, mean mL,(95% CI)2.93(2.09-3.76)2.90(2.08-3.71)3.12(2.51-3.73)2.50(1.55-3.44)p=0.608*p=0.593***Comparisons between pre and post exposure samples were tested using a paired t-test,**Comparisons between pre, post exposure and healthy controls were tested using a one way analysis of variance.ConclusionThis is the largest prospective study ever conducted to evaluate the impact of MTX on semen parameters in men diagnosed with IMDs. We demonstrated that exposure to MTX did not result in statistically significant different semen parameters. Based on semen parameters, our findings suggest that MTX therapy can be continued in men diagnosed with an IMD and a wish to become a father.References[1]Sammaritano LR et al. Arthritis Care Res (Hoboken). 2020;72(4):461-88.[2]Perez-Garcia LF et al. Human Reproduction Update. 2020.Disclosure of InterestsNone declared

Background: Sexual health (SH) can be impaired in men with inflammatory arthritis (IA) (1). In addition to biological factors, such as inflammation, subjective factors such as personal beliefs can also impair SH. The Q methodology combines aspects of qualitative and quantitative approaches to systematically study subjectivity, and has been applied successfully in other medical fields. Objectives: To describe the viewpoints of adult men with IA on the impact of IA on their SH using the Q methodology. Methods: Men, 18 years and older, diagnosed with RA or JIA were invited by their rheumatologist. Participants ranked 34 opinion statements about potential impacts of IA on their SH on an agreement scale. A by-person factor analysis identified common patterns in the rankings. These patterns represent the different viewpoints among the men. Data from interviews, in which the men explained their ranking, was used to further interpret the viewpoints. A Q-methodology study usually consists of 30-40 participants. Results: 30 men with IA were included. Their mean age was 43.2 (range 22–77) years. The analysis revealed three viewpoints: 1.“I am satisfied with my sex life” Men with viewpoint 1 experience no significant impact of IA on their SH. However, most men indicated that when their disease was active, IA had a negative impact on their SH. 2.“Arthritis has a negative influence on my sex life” Men with viewpoint 2 experience a dramatic impact, due to pain, fatigue and gloom. Their relationship worsened and they feel guilty towards their partner. Discussing their problems is not difficult. 3.“I am keeping up appearances” Men with viewpoint 3 experience SH impairment mainly as a result of pain. IA impairs them physically, makes them feel less of a man, less attractive and reduces their self-confidence. Due to problems with accepting their disease and communicating their problems, these men tend to hide their problems. Conclusion: We identified 3 viewpoints on the impact of IA on male SH, 2 of them revealing a negative influence that goes beyond the physical act of sex. IA can also affect relationships, self-confidence and manhood. Future research will focus on identifying men with SH problems in the clinic and the best counseling approach. References: [1]Perez-Garcia LF, Te Winkel B, Carrizales JP, Bramer W, Vorstenbosch S, van Puijenbroek E, et al. Sexual function and reproduction can be impaired in men with rheumatic diseases: A systematic review. Semin Arthritis Rheum. 2020;50(3):557-73. Disclosure of Interests: Luis Fernando Perez-Garcia Consultant of: Galapagos, Esther Röder: None declared, Hester Pastoor: None declared, Hanneke Bolt: None declared, Job van Exel: None declared, Radboud Dolhain Speakers bureau: Abbvie, UCB, Genzyme, Consultant of: Galapagos, Grant/research support from: UCB.

Background: The effect of inflammatory arthritis (IA) on fertility has been mainly studied in women. Multiple factors associated with lower fertility rate in women can also be present in male patients with IA (1). The fertility rate in men with IA, however, has never been studied. Objectives: To describe the fertility rate (number of biological children per individual) of men with IA. Methods: We performed a multicenter cross-sectional retrospective study conducted in eight Dutch hospitals. Men with IA (Rheumatoid Arthritis (RA), Juvenile Idiopathic Arthritis (JIA) and Spondyloarthritis (SpA)) who were over 40 years old and indicated that their family size was complete were invited to participate. Men who were still planning on having biological children were excluded. Participants completed a digital questionnaire that included fertility-related questions and questions regarding their demographic and clinical information. To analyze the impact of IA on male fertility rate, patients were divided into groups according to the age at the time of their diagnosis: age<30 years, age 31-40 years and age>41 years. Results: In total 628 participants diagnosed with IA were included. The response rate 34.87%. Information regarding their age, age at diagnosis, clinical diagnosis and number of children is presented per group in Table 1. Regarding the total number of children per man, there was a statistically significant difference between the three groups (p=<0.005). The mean total number of children was significantly lower in men diagnosed at age<30 years (1.39 {SD 1.41}) and at age 31-40 years (1.60 {SD 1.35}) compared to those diagnosed after at age>41 years (1.88 {SD 1.14}). Compared to men from the general population of the Netherlands, the total number of children of men diagnosed at age>41 years was not statistically different (1.88 vs 1.80, respectively). Table 1. Participants’ basic demographic and clinical characteristics, including the number of biological children per men. All patients IA diagnosed at age <30 years IA diagnosed at age 31-40 years IA diagnosed at age >41 years Total, n (%) 628 137 (21.82) 149 (23.73) 342 (54.46) Age, mean (SD) 57.17 (9.98) 53.01 (9.96) 52.76 (7.35) 61.06 (9.47) Diagnosis, n (%) •iRA 297 (47.29) 42 (30.66) 67 (44.97) 188 (55.32) •AJIA 10 (1.59) 10 (6.25) 0 (0) 0 (0) •ISpA (incl. PsA) 320 (50.96) 90 (65.69) 83 (55.70) 147 (42.98) Age at diagnosis, mean (SD) 41.29 (13.08) 26.27 (9.15) 36.99 (5.66) 49.98 (9.70) Disease duration, mean (SD) 15.89 (11.88) 26.48 (12.57) 15.70 (8.52) 11.30 (9.87) Number of biological children, mean (95% CI) 1.71 (1.60-1.81) 1.39 (1.15-1.63 ) a,b 1.60 (1.38-1.82 ) a 1.88 (1.75 -2.01) a p< 0.05 compared to those diagnosed age >41 years b p< 0.05 compared to those diagnosed age >31-40 years Conclusion: This is the largest study ever conducted to evaluate the impact of IA on male fertility. We demonstrated that men diagnosed with IA before and during their reproductive years have a lower fertility rate than those men diagnosed with IA after their reproductive years. Multiple mechanisms (biological and non-biological) can be responsible for this association. More research is needed to identify the causes of these lower fertility rates in men with IA. References: [1]Perez-Garcia LF, Te Winkel B, Carrizales JP, Bramer W, Vorstenbosch S, van Puijenbroek E, et al. Sexual function and reproduction can be impaired in men with rheumatic diseases: A systematic review. Semin Arthritis Rheum. 2020;50(3):557-73. Figure 1. Total number of biological children (mean and SD) per group. Acknowledgements: The authors would like to acknowledge Ron Buijs, data manager of the Department of Rheumatology of the Erasmus MC, for his technical support with regards to data collection. Disclosure of Interests: Luis Fernando Perez-Garcia Consultant of: Galapagos, Esther Röder: None declared, Robbert Goekoop: None declared, Johanna Hazes: None declared, Marc R Kok Consultant of: Novartis, Grant/research support from: Novartis, Petra Kok: None declared, Hieronymus TW Smeele: None declared, Ilja Tchetverikov: None declared, J.H. van der Kaap: None declared, Annette van der Helm - van Mil: None declared, Bouwe Krijthe: None declared, Radboud Dolhain Speakers bureau: UCB, Roche, Abbvie, Genzyme, Novartis, Consultant of: Galapagos, Grant/research support from: UCB

Background:A treat-to-target approach results in better outcomes for Rheumatoid Arthritis (RA) patients [1]. Well controlled disease is important for pregnant RA patients and patients with a wish to conceive too. Not only for the welfare of the mother, but also because active disease is associated with a prolonged time to pregnancy and adverse pregnancy outcomes [2]. This is this first study to examine a treat-to-target approach during pregnancy.Objectives:To determine the feasibility of a treat-to-target approach in RA patients with a wish to conceive or pregnant.Methods:Patients were derived from the PreCARA cohort (first inclusion 2011, data shown up to November 2019). The PreCARA cohort is an ongoing, single center, prospective study on RA and pregnancy. Patients in this cohort were treated according to a treat-to-target approach, in which the obvious restrictions of pregnancy were taken into account. Study visits were scheduled before, during and after pregnancy and disease activity (DAS28CRP) was measured. Results of the PreCARA study were compared with results of the PARA study [3], a historic reference cohort on RA during pregnancy, with a similar study design (inclusion 2002 – 2010). Patients in the PARA cohort were treated according to the standards of that time. The PARA cohort represents the natural course of RA during pregnancy with limited treatment options.Results:263 RA patients were included in the PreCARA cohort, up to now 154 children were born in this ongoing cohort. Mean age at inclusion was 32.3 (4.3 SD), 83.2 % was Rheumatoid Factor positive and/or ACPA positive. Mean disease activity in the PreCARA cohort is statistically significant lower than in the PARA cohort at every time-point: mean DAS28CRP in 3rdtrimester in the PreCARA cohort 2.22 (0.73 SD), in the PARA cohort 3.35 (1.12 SD) P < 0.001 (figure 1). In the PreCARA cohort 73.3% of the patients were in low disease activity or remission before pregnancy increasing to 90.4 % in the third trimester, whereas in the PARA cohort these percentages were 32.2 % and 47.3% respectively (P < 0.001) (figure 2). Medication use in the PreCARA cohort is shown in table 1 and in the PARA cohort in table 2.MedicationBefore pregnancy (%)*1sttrimester (%)2ndtrimester (%)3rdtrimester (%)6 weeks post-partum (%)12 weeks post-partum (%)26 weeks post-partum (%)MTX5000151915Leflunomide0000112Abatacept0000111Hydroxychloroqine63515150494331Sulfasalazine70565857544736Prednisone43403942383427Azathioprine1211011Certolizumab25212628262418Adalimumab10500334Infliximab5830111Etanercept13109310119Golimumab0000001Tocilizumab3100323* patients seen before pregnancy = 104MedicationBefore pregnancy (%)**1sttrimester (%)2ndtrimester (%)3rdtrimester (%)6 weeks post-partum (%)12 weeks post-partum (%)26 weeks post-partum (%)MTX0000183036Leflunomide0000012Hydroxychloroqine6222487Sulfasalazine34252726263029Prednisone42333636353632Azathioprine1000111Adalimumab0000235Infliximab0000011Etanercept0000365** patients seen before pregnancy = 124Conclusion:This first study on a treat-to-target approach in pregnant RA patients shows that low disease activity and remission are an attainable goal during pregnancy, with over 90% of patients achieving this in the 3rdtrimester. The effect of this approach on fertility and pregnancy outcomes should be the focus of further studies.References:[1]Smolen et al. Rheumatoid arthritis. Lancet 2016[2]Smeele et al. Current perspectives on fertility, pregnancy and childbirth in patients with Rheumatoid Arthritis. Semin Arthritis Rheum 2019[3]de Man et al. Measuring disease activity and functionality during pregnancy in patients with rheumatoid arthritis. A&R 2007Disclosure of Interests:Hieronymus TW Smeele: None declared, Esther Röder: None declared, Hetty Wintjes: None declared, Laura JC Kranenburg - van Koppen: None declared, Johanna Hazes: None declared, Radboud Dolhain Grant/research support from: unrestricted grant from UCB Pharma