Search

BackgroundThe complement system is a key-player in the pathogenesis of systemic lupus erythematosus (SLE); its decreases correlate with disease activity and precedes flare. Since synthesis of complement proteins increase during gestational course, it is debated whether complement levels exert a prognostic role in pregnant women with SLE.ObjectivesWe performed a network meta-analysis to assess the prognostic role of complement in pregnant SLE women, to evaluate the possible role of complement fluctuations during pregnancies.MethodsData from available prospective studies (Jan 2002-Dec 2020) investigating pregnancies in at least 50 SLE patients, excluding miscarriages before 12 weeks, were pooled together. After a systematic literature search, corresponding authors of 19 retrieved studies meeting inclusion criteria were invited to contribute with additional data, including complement levels [6 months before pregnancy, at conception, 1st trimester (T1), 2nd trimester (T2), 3rd trimester (T3) and 3 months after delivery].ResultsA total of 532 SLE women from four eligible studies were included in the analysis [1-4]. Lupus Nephritis (LN) was diagnosed in 237 patients (44.5%) and Antiphospholipid Syndrome in 68 (12.8%). A total of 170 patients (32%) experienced a flare during pregnancy, defined as need of new Immunosuppressants or increase of prednisone > 9 mg/day.Patients with LN had significantly lower mean levels of complement (C3 at conception; C3 at T1; C3 after 3 months of delivery; C4 at all timepoints except for C4 at T3). SLE patients who experienced flares during pregnancy had significantly lower mean levels of complement (all timepoints for both C3 and C4). Table 1 shows the mean C3 and C4 levels in different timepoints according to diagnosis and flare during pregnancy. The lowest levels of complement were observed in patients with a concomitant diagnosis of LN and presence of flare, particularly during the T1 (Figure 1). Nevertheless, both in LN and flare groups the lowest levels of C3 and C4 were documented at T1.Table 1.Complement levels at the different timepoints according to diagnosis or presence of flare (bold results are statistically significant)Patients with LN(237)Patientswithout LN (295)Patients with Flare (170)Patients without Flare (362)Patients with LN and Flare (73)Patients with LN and without Flare (164)C3 6 months before pregnancy (mean ±SD)90.7±18.694.1±25.285.6±19.195.6±23.375 ±17.999.1±12.5C3 conception (mean ±SD)96.1±13.991.1±1395.3±19.591.8±9.197 ±21.695.6±7.1C3 1sttrimester (mean ±SD)84.6±32.298.4±14.178.3±22.8100.5±20.756.8 ±19.997.2±28.7C3 2ndtrimester (mean ±SD)108.5±21108.3±12.294.16±13.4115.7±12.387.5 ±10.9118.6±16.8C3 3rdtrimester (mean ±SD)105.5±15.7108.2±19.198.97±18.6111.4±1698.1 ±12.6109.1±15.8C3 3 months after delivery (mean ±SD)93.4±12103.1±15.492.4±15.7102.6±13.490.5 ±10.894.8±12.3C4 6 months before pregnancy (mean ±SD)15.7±5.514.1±2.811.8±3.916.5±3.310.5±3.418.4±4.2C4 conception (mean ±SD)15.4±4.113.9±2.813.3±3.215.7±3.411±1.317.8±3C4 1sttrimester (mean ±SD)15±7.816.3±2.812.5±5.917.5±4.29.3±7.617.9±6.2C4 2ndtrimester (mean ±SD)17.7±4.718.7±4.215.5±4.319.8±3.713.6±4.119.6±3.5C4 3rdtrimester (mean ±SD)17.8±4.417.5±5.115.7±5.818.6±415.8±4.818.8±3.9C4 3 months after delivery (mean ±SD)16.2±4.319.8±6.914.9±3.920±6.413.3±3.117.6±4Figure 1.Complement Levels during time in patients with Lupus Nephritis and presence, or absence, of flare.ConclusionIn this prospective large cohort of SLE patients low C3/C4 levels, particularly in T1, were associated with a higher frequency of flare. Lowering levels of complement, especially in T1, even within normal range might alert the treating clinicians in predicting disease course and consequently avoid flares, especially in LN.References[1]Saavedra MÁ et al. Int J Rheum Dis 2020[2]Moroni G et al. J Autoimmun 2016[3]Rodrigues BC et al. Lupus 2019[4]Borella E et al. Immunol Res 2014Disclosure of InterestsNone declared

BackgroundApremilast (APR) is an oral PDE4 inhibitor approved for the treatment of Psoriatic Arthritis (PsA). Its effectiveness has been assessed in clinical trials1,2, but real-life data are still scarce.ObjectivesTo evaluate the retention rate (RR) of APR in PsA patients and the risk factors associated to APR inadequate response.MethodsRetrospective monocentric analysis of PsA patients (CASPAR criteria 2006) treated with APR between 2017 and 2021. Disease activity was evaluated at baseline (T0) and after 6 (T6), 12 (T12) and 24 (T24) months of therapy using DAPSA score. Data are expressed as median [IQR].ResultsThe cohort included 79 patients (41% males; age at PsA onset: 47 [37-58] years). PsA domains were: oligoarticular involvement (58%), enthesitis (42%), dactylitis (6%), axial involvement (13%), psoriasis (62%).Half patients presented dysmetabolic traits: 47% overweight/obesity, 34% arterial hypertension, 20% dyslipidemia.APR was prescribed mainly as first-line targeted therapy; in 42% APR was administered after the failure of ≥1 bDMARD.Contraindications to bDMARDs (47%) especially increased infectious risk (19/37) and current/previous malignancy (15/37), and mild PsA phenotype (27%) were the main reasons for APR choice.APR was discontinued in 61% after 4 [1-10] months because of inefficacy (25/48) or adverse events (AEs) (21/48; 81% gastrointestinal complaints). Patients who discontinued APR were compared with patients who continued APR (Table 1).Table 1.APR WITHDRAWALn=48APR CONTINUATIONn=31p valueFemales28 (58)19 (61)0.79Age at T0, years51 [44-58]57 [53-71]0.03PsA duration at T0, years5 [2-11]5 [0-12]0.81Oligoarticular involvement24 (50)20 (65)0.21Axial involvement6 (13)4 (13)1.00Enthesitis / dactylitis26 (54)11 (36)0.10DAPSA at T022 [16-28]18 [13-26]0.27APR in monotherapy26 (54)23 (74)0.07bDMARDs naïve24 (50)22 (71)0.07Results are presented as median [IQR] or number (%). Continuous variables were compared with Mann-Whitney test; categorical variables were compared with Chi Squared/exact Fisher test.The RR of APR was 62% at T6, 51% at T12 and 38% at T24 (Figure 1a).Figure 1.a) Overall RR of APR b) RR of APR in bDMARDs naïve vs previously treated with bDMARDs patients (exclusion of withdrawals for intolerance).In patients continuing therapy, APR showed a good efficacy, with a significant reduction of DAPSA score observed at T6 (13 [9-19]), T12 (11 [4-18]) and T24 (8 [3-10]) as compared to T0 (21 [14-28]) (pAn overall trend of reduction of the BMI (kg/m2) was observed (T0: 25 [22-28], T6: 24 [21-27], T12: 23 [21-26]); in overweight patients the BMI decreased significantly (28 [26-31] at T0 vs 27 [26-29] at last evaluation; pBecause of the high rate of discontinuations due to intolerance in the first months of therapy, we conducted a sub analysis: patients who continued APR (n=31) vs patients who discontinued it for inefficacy (n=25). A higher frequency of APR withdrawal was registered in younger patients (51 [47-57] vs 57 [53-71] years; p:0.01) previously treated with bDMARDs (71% vs 40%; p:0.02). Multivariate analysis confirmed these associations (OR [95% CI]: 0.1 [0.89-0.99], p:0.03 and 2.3 [1.70-59.17], p:0.01; respectively). The RR was higher in bDMARDs naïve patients compared with patients previously treated with bDMARDs (T6: 75% vs 67%, T12: 71% vs 63%, T24: 67% vs 34%; log-rank test= p:0.05) (Figure 1b).ConclusionThis study confirms the safety and effectiveness of APR in a real-life scenario. We experienced a higher APR withdrawal rate for AEs (44%) in the first months of therapy, compared to registration studies in which APR was suspended in (8%). However, when tolerated, APR maintained efficacy over time, as demonstrated by progressive DAPSA reduction. The higher RR in bDMARDs naïve patients suggests the early use of APR. Moreover, the reduction of BMI could favor APR use in dysmetabolic patients. These data need to be confirmed in larger studies.References[1]Edwards CJ et al. Ann Rheum Dis. 2016. 1Kavanaugh A et al. Arthritis Res Ther. 2019.Disclosure of InterestsNone declared

BackgroundAntiphospholipid Syndrome (APS) is a rare autoimmune disease characterized by thrombotic events and/or pregnancy morbidities in the presence of confirmed positivity for antiphospholipid antibodies (aPL). Complement was demonstrated to be involved in aPL-related pregnancy loss in animal models and several groups investigated the significance of complement levels in human disease. C3 and C4 serum levels were assessed in several cohorts of pregnant patients with APS and/or aPL positivity in order to relate complement consumption with adverse pregnancy outcome (APO).According to some authors, hydroxychloroquine (HCQ) can control the activation of the complement system, improve pregnancy outcome and reduce aPL title.ObjectivesThis study was designed to verify the effect of HCQ in addition to low dose aspirin (LDA) + low molecular weight heparin (LMWH) treatment in a multicenter cohort of primary APS (PAPS) and aPL carriers pregnant women and the possible correlation with preconception serum C3/C4 levels.MethodsMedical records of pregnant women with confirmed positivity for aPL antibodies attending twelve referral centers from January 2010 to December 2020 were retrospectively evaluated. We considered as aPL-related APO: spontaneous abortions (ResultsWe have analyzed 164 singleton PAPS/aPL carrier pregnancies (22 aPL carriers - 13%) in 128 patients: all were treated with combination therapy (LDA+LMWH), and in 30 HCQ was added. 58 pregnancies (43%) had low levels of preconception C3/C4. A triple aPL positivity was observed in 54 pregnancies, 14 of them were treated with combination therapy + HCQ. When considering the whole cohort, the addition of HCQ had not significantly improved the gestational outcome. Further stratification was performed on the basis of complement consumption. In the group of patients with preconception low C3/C4 levels the addition of HCQ had not significantly improved pregnancy outcome. We have lastly evaluated 40 pregnancies with a high-risk profile (triple aPL positivity and complement consumption), in which we have found that HCQ significantly improved gestational outcome (p=0.018, Table 1).Table 1.Relationship between APO, therapy during pregnancy and risk profile.All pregnancies (n=164)Reduced C3/C4 (n=58)Triple aPL+ and reduced C3/C4 (n=40)LDA+LMWH (n, %)LDA+LMWH+HCQ (n, %)pLDA+LMWH (n, %)LDA+LMWH+HCQpLDA+LMWHLDA+LMWH+HCQp(n, %)(n, %)(n, %)APO62 (46%)16 (53%)ns32 (68%)4 (36%)ns23 (77%)3 (30%)0.018No APO72 (54%)14 (47%)15 (32%)7 (64%)7 (23%)7 (70%)Total1343047113010This observation could not be confirmed in patients with single or double aPL positivity.ConclusionThe study shows that administering HCQ in addition to combination therapy can improve gestational outcome in aPL/PAPS high-risk patients. This observation confirms that HCQ exerts a beneficial effect on aPL pregnancies by complement inhibition as it was shown in animal models. In addition, our results provide the clinicians a useful tool to implement conventional treatment in patients at high risk of pregnancy complication or loss.References[1]De Carolis S, et al. Is there any role for the hydroxychloroquine (HCQ) in refractory obstetrical antiphospholipid syndrome (APS) treatment? Autoimmun Rev 2015;14:760-2.[2]Mekinian A, et al. The efficacy of hydroxychloroquine for obstetrical outcome in antiphospholipid syndrome: data from a European multicenter retrospective study. Autoimmun Rev 2015;40:498-502.[3]Mekinian A et al. Obstetrical APS: is there a place for hydroxychloroquine to improve the pregnancy outcome? Autoimmun Rev 2015;14:23-9.Disclosure of InterestsNone declared

BackgroundThere is growing interest in reproductive issues in patients with Spondyloarthritis (SpA) and Psoriatic arthritis (PsA).ObjectivesTo describe a real-life cohort of prospectively-followed pregnancies in SpA and PsA patients, focusing on obstetric outcome and on flare during pregnancies and post-partum.MethodsData on SpA and PsA pregnancies prospectively-followed in 2 European pregnancy clinics from 2010 to 2021 were retrospectively analysed.Disease activity was assessed using ASDAS-CRP or DAS28-CRP according to the main involvement (peripheral or axial). Disease flare was defined as the need to treatment modification (introduction or increase ≥5mg/day of prednisone, introduction of cDMARD or bDMARD). Miscarriages were excluded from the analysis of flares.ResultsData on 122 pregnancies (53 PsA and 69 ‘other SpA’: 39 axialSpA, 20 undifferentiated SpA, 6 IBD-related SpA, 4 reactive arthritis) in 102 patients (median age at conception: 34 [IQR: 31-36] years; median disease duration: 72 [24-132] months) were collected.We recorded 98 (86%) live births and 16 (14%) miscarriages (8 missing data).Cesarean section was performed in 15/98 (15%) cases. Median week of gestation at delivery was 39 [38-40]; 8 preterm births (Fourty-two pregnancies (40%) had at least 1 flare during pregnancy; 7 pregnancies had more than 1 flare. Overall, there were 13, 24 and 12 flares in the 1st, 2nd and 3rd trimester, respectively.A higher frequency of patients with axial involvement was observed in the ‘flare’ group as compared to pregnancies without flare (83% vs 59%, p=0.02) (Table 1).Table 1.Comparison between ‘flare’ and ‘without flare’ groups.FLARE (42)WITHOUT FLARE (64)pAge at conception (years)33 (31-37)33 (31-35)0.88Disease duration at conception (months)71 (24-120)60 (24-137)0.74PsA13 (31%)31 (48%)0.11‘Other SpA’29 (69%)33 (52%)0.11Axial involvement35 (83%)38 (59%)0.02Peripheral involvement30 (%)54 (%)0.17bDMARD useAny time before pregnancy16 (38%)19 (30%)0.49Stop at + pregnancy test/1st trimester8 (19%)4 (6%)0.09Start/continue 1st trimester7 (17%)10 (16%)0.89Start in 2ndtrimester5 (12%)00.02Start in 3rd trimester2 (5%)00.30Post-partum flare11/34 (32%)22/49 (45%)0.36Continuous variables were compared using Mann-Whitney test; categorical variables were compared using Chi-square with Yates’ correction or Fisher’s exact test.Medications resumed to treat flare were steroids (29 pregnancies), csDMARDs (14 pregnancies) and TNF-inhibitors (7 pregnancies: 5 during the 2nd and 2 during the 3rd trimester).A post-partum flare was registered in 33/83 (40%) of cases, without difference between ‘flare’ group vs ‘without flare’ group (Table 1), as well as between PsA vs ‘other SpA’ pregnancies (47% vs 33%, p=0.2).ConclusionIn this cohort of SpA pregnancies, 40% experienced a flare during pregnancy and 40% during post-partum. Flares occurred more frequently in the 2nd trimester and especially in patients with axial involvement, requiring the start of a TNF-inhibitor during the 2nd or the 3rd trimester in 7 pregnancies. Having a flare during pregnancy was not associated with a post-partum flare.Disclosure of InterestsNone declared