Considering belimumab during pregnancy: A more viable option over time.

OBJECTIVE: To share our experience with belimumab in lupus pregnant women and to review the relevant published literature on its use in this scenario. METHODS: A prospective observational study of pregnant patients with lupus was conducted. Additionally, MEDLINE and EMBASE databases were searched, and a secondary hand search of the literature was performed. Studies were evaluated and visualised descriptively. RESULTS: Sixteen pregnancies of 12 lupus women were included, six (involving eight pregnancies) received belimumab throughout their illness, five of them during some period of gestation. In this group, there was one miscarriage, one elective termination and seven live foetuses (including two live twins). There was one type I intrauterine growth retardation, and a preterm pregnancy due to premature rupture of membranes (PPROM). One mild lupus flare was detected. There were no cases of pre-eclampsia, gestational diabetes mellitus or hypertension. All neonates had normal Apgar scores at birth, none needed critical care. There were no congenital anomalies. After the search, we identified 10 case reports and case series, and five registries. Among the 39 reported cases (41 pregnancies), there were 5 PPROM, 4 pre-eclampsia, and 1 eclampsia. All women made full recoveries. Nineteen new-borns had low birth weight. There were no malformations. While registries did not indicate an increased risk of birth defects or pregnancy loss, there was a higher risk of neonatal infections. CONCLUSIONS: Belimumab may be an option for pregnant women with difficult-to-control lupus. Further research is needed to confirm the absence of association between belimumab and foetal harm.

Lack of awareness of systemic lupus erythematosus and its consequences in a cohort of moderate and severe patients in Spain: The LupusVoice study.

BACKGROUND AND OBJECTIVES: Systemic lupus erythematosus (SLE) is an autoimmune condition that can highly impact patients' quality of life (QoL). However, there is a lack of knowledge about SLE, affecting the general population and health care professionals (HCPs) alike. This lack of knowledge has negative implications for patients and the healthcare system, worsening prognosis, negatively impacting QoL, and increasing healthcare utilization. The aim of this paper is to draw attention, according to the perspective of the participants of this study, to the lack of awareness of SLE and its consequences in Spain, and to suggest improvements. PATIENTS AND METHODS: This qualitative, descriptive, observational, multicenter, and cross-sectional study included 40 patients with moderate or severe SLE, recruited during their routine visits in six university hospitals in Spain. The study also included 11 caregivers and 9 HCPs. All participants were individually interviewed. Data from the interviews were coded and analyzed thematically by two anthropologists following a phenomenological perspective. RESULTS: Our study identified a lack of disease awareness among primary care physicians, emergency medicine doctors, and other specialists treating SLE symptomatology. This led to diagnostic delays, which had a clinical and emotional impact on patients. Furthermore, symptom awareness was found to be context dependent. Differences in symptom awareness between HCPs and patients led to a mismatch between the severity evaluation made by doctors and patients. Some HCPs did not consider the limitations of the current severity evaluation of SLE, and therefore attributed symptoms potentially caused by SLE to the unfavorable socioeconomic conditions patients lived in. Finally, a lack of social awareness among friends, family members, and romantic partners led to lower social support, increased isolation, and negative physical and emotional impact for patients. Gender differences in the provision of support were identified. CONCLUSION: This study highlights the need to increase SLE awareness among patients, HCPs, and the broader public in order to improve patient QoL. Being aware of the clinical and emotional impact of such lack of awareness, as well as the role played by context on the patient experience of SLE, is a crucial step towards achieving this goal.

Nintedanib in chronic fibrosing interstitial lung diseases. A case series.

Progressive pulmonary fibrosis (PPF) can be fatal in non-idiopathic interstitial lung diseases. We report a descriptive series of 13 patients with PPF who received treatment with nintedanib, a multitargeted tyrosine kinase inhibitor with antifibrotic effect. Although the reduced number of patients and the observational nature of a case series prevent us from providing strong evidence, our results suggest that nintedanib could be effective in PPF of various etiologies. Nintedanib could also be useful in specific populations such as patients awaiting lung transplant and elderly patients.

Real-world persistence of initial targeted therapy strategy in monotherapy versus combination therapy in patients with chronic inflammatory arthritis.

OBJECTIVE: The persistence of biologic (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs(DMARDs) in monotherapy versus in combination with conventional synthetic (cs) DMARDs is still a controversial topic in rheumatic diseases. To clarify this issue, the retention of the initial treatment strategy of b/tsDMARD in combination with csDMARD versus monotherapy in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients under real-life conditions was evaluated. Factors associated with maintenance of the initial strategy were analysed. METHODS: Nested cohort study within the Spanish BIOBADASER III registry. Bivariate comparisons and multivariate Cox proportional hazards models were used for the analyses. RESULTS: A total of 2521 patients were included in the study. In the multivariate model, the initial strategy of combination therapy was associated with shorter persistence in patients with RA (hazard ratio [HR] 1.58;95% confidence interval [CI] 1.00-2.50; p = .049), PsA (HR 2.48; 95% CI 1.65-3.72) and AS (HR 16.77; 95% CI 7.37-38.16; p < .001), regardless of sex, time of disease progression, baseline disease activity, glucocorticoid use or type of b/tsDMARD. Overall, the combination strategy was associated with an increased incidence of adverse events (incidence rate ratio [IRR] 1.13; 95% CI 1.05-1.21). CONCLUSIONS: In this real-life study, the strategy of combining a b/tsDMARD with a csDMARD is associated with lower persistence and worse safety profile compared to monotherapy in RA and especially in PsA and AS, suggesting that combination therapy should be rethought as first choice in RA patients, but especially in PsA and AS patients.

Agreement Among Multiple Observers on Crystal Identification by Synovial Fluid Microscopy.

OBJECTIVE: Despite the fact that polarized microscopy remains the gold standard for diagnosing crystal arthritis, some uncertainties hamper full implementation in clinical practice. We undertook this study to analyze the agreement among multiple observers in crystal identification using compensated polarized microscopy, as well as to assess potential outcome modifiers. METHODS: This was a cross-sectional, observational study with consecutive synovial fluid sampling. Samples were immediately analyzed when possible or kept refrigerated at 4°C. Five observers analyzed them separately, blinded to clinical data, using a compensated polarized optical microscope (400×), through 3 stages (ordinary, simple polarized, and compensated polarized light) to detect and identify crystals. They recorded the presence and type of crystal (no crystals, monosodium urate [MSU], and calcium pyrophosphate dihydrate [CPP]). Interrater agreement was measured by Cohen's kappa. Subanalyses were performed on visualization delay and cumulative expertise. Discrepancies between each stage of the microscopy and the final decision were also examined. RESULTS: A total of 250 observations from 50 samples completed full assessment. Overall, κ = 0.74 (95% confidence interval [95% CI] 0.64-0.84), indicating good agreement. Agreement for crystal detection was κ = 0.71 (95% CI 0.59-0.82), for MSU was κ = 0.88 (95% CI 0.75-1.0), and for CPP was κ = 0.69 (95% CI 0.56-0.82). Most of the crystal identifications were already made by ordinary light. No differences between observations made before or after 24 hours (P = 0.859) or in expertise on crystal analysis (P = 0.989) were found. Observations performed under ordinary light matched the final diagnosis in 96.8% of cases (242 of 250). CONCLUSION: Compensated polarized microscopy remained consistent in detecting and identifying crystals in synovial fluid, even when examined among multiple observers, confirming its high utility for clinical practice.

Systematic review of the impact of drugs on diffuse interstitial lung disease associated with rheumatoid arthritis.

OBJECTIVE: To review the available evidence on the impact of rheumatoid arthritis (RA) treatments in associated diffuse interstitial lung disease (ILD). METHODS: Systematic review of studies evaluating the impact of pharmacological treatment in patients with RA and ILD. A bibliographic search in MEDLINE, EMBASE and Cochrane, a selection of articles and the methodological quality assessment (FLC 3.0 OSTEBA) and grading of the level of evidence (SING) of the selected articles were performed. RESULTS: 1,720 references were identified in primary search and 7 in manual or indirect. Forty-three articles were included: 7 systematic reviews, 2 randomized clinical trials, 5 cohort studies, 8 case-control studies and 21 case series. Methotrexate (MTX) and leflunomide (LEF) do not increase incidence, complications or mortality due to ILD. Although the results are not uniform, anti-TNF have often had worse outcomes in incidence, progression and mortality due to ILD than MTX, LEF, abatacept (ABA) and rituximab (RTX). The evidence found is scarce for JAK kinase and antifibrotic inhibitors, and controversial for IL-6 inhibitors. CONCLUSIONS: There is no evidence that MTX or LEF worsens the prognosis of patients with AR-EPID. RTX and ABA seem to have better results than other biologicals, such us TNFi, often achieving stabilization and, in some cases, the improvement of ILD in patients with RA.

Changes in the use patterns of bDMARDs in patients with rheumatic diseases over the past 13 years.

The better understanding of the safety of biologic DMARDs (bDMARDs), as well as the emergence of new bDMARDs against different therapeutic targets and biosimilars have likely influenced the use patterns of these compounds over time. The aim of this study is to assess changes in demographic characteristics, disease activity and treatment patterns in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) who started a first- or second-line biologic between 2007 and mid-2020. Patients diagnosed with RA, PsA or AS included in the BIOBADASER registry from January 2007 to July 2020 were included. According to the start date of a first- or second-line biologic therapy, patients were stratified into four time periods: 2007-2009; 2010-2013; 2014-2017; 2018-2020 and analyzed cross-sectionally in each period. Demographic and clinical variables, as well as the type of biologic used, were assessed. Generalized linear models were applied to study the evolution of the variables of interest over time periods, the diagnosis, and the interactions between them. A total of 4543 patients initiated a first biologic during the entire time frame of the study. Over the four time periods, disease evolution at the time of biologic initiation (p < 0.001), disease activity (p < 0.001), retention rate (p < 0.001) and the use of tumor necrosis factor inhibitors as a first-line treatment (p < 0.001) showed a significant tendency to decrease. Conversely, comorbidities, as assessed by the Charlson index (p < 0.001), and the percentage of patients using bDMARDs in monotherapy (p < 0.001), and corticosteroids (p < 0.001) tended to increase over time. Over the entire period of the study's analysis, 3289 patients started a second biologic. The following trends were observed: decreased DAS28 at switching (p < 0.001), lower retention rates (p = 0.004), and incremental changes to the therapeutic target between the first and second biologic (p < 0.001). From 2007 until now rheumatic patients who started a biologic were older, exhibited less clinical activity, presented more comorbidities, and switched to a different biologic more frequently and earlier.

Influence of prognosis factors on the prescription of targeted treatments in rheumatoid arthritis: A Delphi survey.

OBJECTIVES: To explore current evidence on the management of poor prognostic factors in rheumatoid arthritis (RA) and to investigate whether this evidence is taken into account by clinicians when deciding on treatment in daily clinical practice. METHODS: We performed a systematic literature review (SLR) to analyse the effects of currently available biologic disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKi) on the classically accepted poor prognostic factors of RA. All randomized controlled trials reporting subgroup analyses about effects on prognostic factors were identified and synthesized. In a second phase, a two-round Delphi survey was carried out to contrast the SLR results with the grade of agreement of a large group of rheumatologists about the effectiveness of each drug class on each prognostic factor. RESULTS: According to the Delphi results, the only prognostic factor that significantly influenced the selection of treatment was the presence of interstitial lung disease (ILD), being the preferred treatment in this scenario abatacept or rituximab. The rest of the poor prognostic factors (including high disease activity at baseline, disability as measured by the Health Assessment Questionnaire index, seropositivity, elevated acute-phase reactants, and evidence of erosions based on plain radiography or ultrasonography) did not seem to significantly influence rheumatologists when choosing a treatment. The results of the SLR results did not show solid evidence regarding the use of any specific therapy in the management of patients with specific poor factors, except in the case of RA-ILD, although the data in the literature in this regard are not free of bias. CONCLUSIONS: The only prognostic factor that seems to significantly influence the selection of treatment is the presence of RA-ILD.

Pneumocystis jirovecii in immunocompromised patients with rheumatic diseases. / Pneumocystis jirovecii en pacientes inmunocomprometidos con enfermedades reumáticas.

Infections, including opportunistic infections, are a major and frequent cause of morbidity and mortality in patients with systemic autoimmune and rheumatic diseases. Pneumocystis jirovecii pneumonia, classically considered to be typical of HIV patients, transplanted patients or patients treated with oncological chemotherapy, is appearing increasingly frequently in these patients. Therefore, rheumatologists should know its mechanism of production, clinical manifestations, treatment and prophylaxis, all of which are addressed in this review.

Pregnancy control in patients with systemic lupus erythematosus/antiphospholipid syndrome. Part 2: Pregnancy follow-up. / Control del embarazo en pacientes con lupus eritematoso sistémico/síndrome antifosfolípido. parte 2: seguimiento del embarazo.

OBJECTIVE: In order to agree on the fundamental aspects related to the management of pregnancy in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS), the Spanish Societies of Gynaecology and Obstetrics, Internal Medicine and Rheumatology set up a working group for the preparation of three consensus documents. METHODS: Each of the Scientific Societies involved proposed five representatives based on their experience in the field of pregnancy control in patients with autoimmune diseases. The recommendations were developed following the Delphi methodology. RESULTS: This second document contains the recommendations regarding the management of pregnancy in women with SLE and APS, including complications such as lupus activity, congenital heart block, thrombotic and obstetric manifestations of APS and placental vascular disease. CONCLUSIONS: These multidisciplinary recommendations are considered decision-making tools for clinicians involved in the care of patients with SLE/APS during pregnancy.

Pregnancy Control in Patients with Systemic Lupus Erythematosus and Antiphospholipid Syndrome. Part 1: Infertility, Ovarian Preservation and Preconception Assessment. Consensus Document of the Spanish Society of Gynaecology and Obstetrics (SEGO), the Spanish Society of Internal Medicine (SEMI) and the Spanish Society of Rheumatology (SER). / Control del embarazo en pacientes con lupus eritematoso sistémico y síndrome antifosfolípido. Parte 1: Infertilidad, preservación ovárica y valoración preconcepcional. Documento de consenso de la Sociedad Española de Ginecología y Obstetricia (SEGO), Sociedad Española de Medicina Interna (SEMI) y Sociedad Española de Reumatología (SER).

OBJECTIVE: Pregnancy and puerperium are considered a risk situation in women with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Therefore, specialized assessment is essential both preconception and during pregnancy and the puerperium. Likewise, it is very important that different specialists in autoimmune diseases and high-risk pregnancies participate in the follow-up of these patients in a coordinated manner. The Spanish Society of Gynaecology and Obstetrics, the Spanish Society of Internal Medicine, and the Spanish Society of Rheumatology have set up a working group for the preparation of three consensus documents. METHODS: The stages of the work were: distribution of work in three groups corresponding to the three periods related to pregnancy (preconception, during pregnancy and childbirth and puerperium), identification of key areas, exhaustive review of the literature and formulation of recommendations. RESULTS: This first document includes the 48 recommendations that address aspects related to infertility, the need for and treatments for gonadal preservation and preconception assessment. CONCLUSIONS: These multidisciplinary recommendations are considered decision-making tools for clinicians involved in the care of patients with SLE/APS during pregnancy.

Pregnancy control in Patients with Systemic Lupus Erythematosus/Antiphospholipid Syndrome. Part 3: Childbirth. Puerperium. Breastfeeding Contraception. Newborn. / Control del embarazo en pacientes con lupus eritematoso sistémico/síndrome antifosfolípido. Parte 3. Parto. Puerperio. Lactancia. Anticoncepción. Recién nacido.

OBJECTIVE: In order to agree on the fundamental aspects related to the management of pregnancy in patients with systemic lupus erythematosus and antiphospholipid syndrome, the Spanish Societies of Gynaecology and Obstetrics, Internal Medicine and Rheumatology have set up a working group for the preparation of three consensus documents. METHODS: Each of the Scientific Societies involved proposed five representatives based on their experience in the field of pregnancy control in patients with autoimmune diseases. The recommendations were developed following the Delphi methodology. RESULTS: This third document contains the recommendations regarding the management of delivery, puerperium and lactation, including medication use during these periods and the care of the newborn. In addition, a section on contraception is included. CONCLUSIONS: These multidisciplinary recommendations are considered decision-making tools for clinicians involved in the care of patients with systemic lupus erythematosus/antiphospholipid syndrome during pregnancy.

Abatacept in interstitial lung disease associated with rheumatoid arthritis: national multicenter study of 263 patients.

OBJECTIVE: To assess the efficacy of abatacept (ABA) in RA patients with interstitial lung disease (ILD) (RA-ILD). METHODS: This was an observational, multicentre study of RA-ILD patients treated with at least one dose of ABA. ILD was diagnosed by high-resolution CT (HRCT). We analysed the following variables at baseline (ABA initiation), 12 months and at the end of the follow-up: Modified Medical Research Council (MMRC) scale (1-point change), forced vital capacity (FVC) or diffusion lung capacity for carbon monoxide (DLCO) (improvement or worsening ≥10%), HRCT, DAS on 28 joints evaluated using the ESR (DAS28ESR) and CS-sparing effect. RESULTS: We studied 263 RA-ILD patients [150 women/113 men; mean (s.d.) age 64.6 (10) years]. At baseline, they had a median duration of ILD of 1 (interquartile range 0.25-3.44) years, moderate or severe degree of dyspnoea (MMRC grade 2, 3 or 4) (40.3%), FVC (% of the predicted) mean (s.d.) 85.9 (21.8)%, DLCO (% of the predicted) 65.7 (18.3) and DAS28ESR 4.5 (1.5). The ILD patterns were: usual interstitial pneumonia (UIP) (40.3%), non-specific interstitial pneumonia (NSIP) (31.9%) and others (27.8%). ABA was prescribed at standard dose, i.v. (25.5%) or s.c. (74.5%). After a median follow-up of 12 (6-36) months the following variables did not show worsening: dyspnoea (MMRC) (91.9%); FVC (87.7%); DLCO (90.6%); and chest HRCT (76.6%). A significant improvement of DAS28ESR from 4.5 (1.5) to 3.1 (1.3) at the end of follow-up (P < 0.001) and a CS-sparing effect from a median 7.5 (5-10) to 5 (2.5-7.5) mg/day at the end of follow-up (P < 0.001) was also observed. ABA was withdrawn in 62 (23.6%) patients due to adverse events (n = 30), articular inefficacy (n = 27), ILD worsening (n = 3) and other causes (n = 2). CONCLUSION: ABA may be an effective and safe treatment for patients with RA-ILD.

Systematic Review of the Impact of Drugs on Diffuse Interstitial Lung Disease Associated with Rheumatoid Arthritis. / Revisión sistemática sobre el impacto de los fármacos en la enfermedad pulmonar intersticial difusa asociada a Artritis Reumatoide.

OBJECTIVE: To review the available evidence on the impact of rheumatoid arthritis (RA) treatments in associated diffuse interstitial lung disease (ILD). METHODS: Systematic review of studies evaluating the impact of pharmacological treatment in patients with RA and ILD. A bibliographic search in MEDLINE, EMBASE and Cochrane, a selection of articles and the methodological quality assessment (FLC 3.0 OSTEBA) and grading of the level of evidence (SING) of the selected articles were performed. RESULTS: 1,720 references were identified in primary search and 7 in manual or indirect. Forty-three articles were included: 7 systematic reviews, 2 randomized clinical trials, 5 cohort studies, 8 case-control studies and 21 case series. Methotrexate (MTX) and leflunomide (LEF) do not increase incidence, complications or mortality due to ILD. Although the results are not uniform, anti-TNF have often had worse outcomes in incidence, progression and mortality due to ILD than MTX, LEF, abatacept (ABA) and rituximab (RTX). The evidence found is scarce for JAK kinase and antifibrotic inhibitors, and controversial for IL-6 inhibitors. CONCLUSIONS: There is no evidence that MTX or LEF worsens the prognosis of patients with AR-EPID. RTX and ABA seem to have better results than other biologicals, such as anti-TNF, often achieving stabilization and, in some cases, the improvement of ILD in patients with RA.

A composite indicator to assess the quality of care in the management of patients with rheumatoid arthritis in outpatient rheumatology clinics. / Indicador compuesto para evaluar la calidad asistencial en el manejo de los pacientes con artritis reumatoide en las consultas externas de Reumatología.

OBJECTIVE: The current guidelines in the treatment of rheumatoid arthritis (RA) include the early diagnosis and early use of disease modifying drugs to achieve remission or low disease activity level, known as "Treat to Target" (T2T). The objective of this study is to develop a composite indicator (CI) to evaluate the quality of care in the management of patients with RA, according to the T2T strategy and other general recommendations concerning the management of these patients. MATERIAL AND METHOD: The phases of the construction of the CI were: 1) selection of quality criteria through expert judgment; 2) prioritization of the criteria, according to relevance and feasibility, applying the Delphi methodology (two rounds) involving 20 experts; 3) design of quality indicators; and 4) calculation of the weighted CI, using the mean value in relevance and feasibility granted by the experts. The source of information for the calculation of the CI are the medical records of patients with RA. RESULTS: Twelve criteria out of 37 required a second Delphi round. Thirty-one criteria were prioritized. These criteria presented a median in relevance and feasibility greater than or equal to 7.5, with an interquartile range of less than 3.5, and a level of agreement (score greater than or equal to 8) greater than or equal to 80%. CONCLUSIONS: The constructed CI allows us to evaluate the quality of care of patients with RA following the T2T strategy in the rheumatology units of Spanish hospitals, offering a valid and easily interpretable summary measure.

Abatacept in patients with rheumatoid arthritis and interstitial lung disease: A national multicenter study of 63 patients.

OBJECTIVE: Interstitial lung disease (ILD) is one of the most serious complications of rheumatoid arthritis (RA). In the present study, we aimed to assess the efficacy of abatacept (ABA) in patients with ILD associated to RA. METHODS: National multicenter, non-controlled, open-label registry study of RA patients with ILD treated with ABA. RESULTS: 63 patients (36 women) with RA-associated ILD undergoing ABA therapy were studied. The mean ± standard deviation age at the time of the study was 63.2 ± 9.8 years. The median duration of RA and ILD from diagnosis were 6.8 and 1 year, respectively. RA was seropositive in 55 patients (87.3%). In 15 (23.8%) of 63 patients the development of ILD was closely related to the administration of synthetic or biologic disease modifying anti-rheumatic drugs. After a follow-up of 9.4 ± 3.2 months, two-thirds of patients remained stable whereas one-quarter experienced improvement in the Modified Medical Research Council scale. At that time forced vital capacity remained stable in almost two-thirds of patents and improved in one out of five patients assessed. Also, diffusing capacity of the lung for carbon monoxide remained stable in almost two-thirds and showed improvement in a quarter of the patients assessed. At 12 months, 50% of the 22 patients in whom chest HRCT scan was performed due persistence of respiratory symptoms showed stabilization, 8 (36.4%) improvement and 3 worsening of the HRCT scan pattern. Eleven of 63 patients had to discontinue ABA, mainly due to adverse events. CONCLUSION: ABA appears to be an effective in RA-associated ILD.

Certolizumab pegol (CDP870) for rheumatoid arthritis in adults.

BACKGROUND: Tumour necrosis factor (TNF)-alpha inhibitors are beneficial for the treatment of rheumatoid arthritis (RA) for reducing the risk of joint damage, improving physical function and improving the quality of life. This review is an update of the 2014 Cochrane Review of the treatment of RA with certolizumab pegol. OBJECTIVES: To assess the clinical benefits and harms of certolizumab pegol (CZP) in people with RA who have not responded well to conventional disease-modifying anti-rheumatic drugs (DMARDs). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL: Cochrane Library 2016, Issue 9), MEDLINE, Embase, Web of Knowledge, reference lists of articles, clinicaltrials.gov and ICTRP of WHO. The searches were updated from 2014 (date of the last search for the previous version) to 26 September 2016. SELECTION CRITERIA: Randomised controlled trials that compared certolizumab pegol with any other agent, including placebo or methotrexate (MTX), in adults with active RA, regardless of current or prior treatment with conventional disease-modifying anti-rheumatic drugs (DMARDs), such as MTX. DATA COLLECTION AND ANALYSIS: Two review authors independently checked search results, extracted data and assessed trial quality. We resolved disagreements by discussion or referral to a third review author. MAIN RESULTS: We included 14 trials in this update, three more than previously. Twelve trials (5422 participants) included measures of benefit. We pooled 11 of them, two more than previously. Thirteen trials included information on harms, (5273 participants). The duration of follow-up varied from 12 to 52 weeks and the range of doses of certolizumab pegol varied from 50 to 400 mg given subcutaneously. In Phase III trials, the comparator was placebo plus MTX in seven trials and placebo in five. In the two Phase II trials the comparator was only placebo.The approved dose of certolizumab pegol, 200 mg every other week, produced clinically important improvements at 24 weeks for the following outcomes:- American College of Rheumatology (ACR) 50% improvement (pain, function and other symptoms of RA): 25% absolute improvement (95% confidence interval (CI) 20% to 33%); number need to treat for an additional beneficial outcome (NNTB) of 4 (95% CI 3 to 5); risk ratio (RR) 3.80 (95% CI 2.42 to 5.95), 1445 participants, 5 studies.- The Health Assessment Questionnaire (HAQ): -12% absolute improvement (95% CI -9% to -14%); NNTB of 8 (95% CI 7 to 11); mean difference (MD) - 0.35 (95% CI -0.43 to -0.26; 1268 participants, 4 studies) (scale 0 to 3; lower scores mean better function).- Proportion of participants achieving remission (Disease Activity Score (DAS) < 2.6) absolute improvement 10% (95% CI 8% to 16%); NNTB of 8 (95% CI 6 to 12); risk ratio (RR) 2.94 (95% CI 1.64 to 5.28), 2420 participants, six studies.- Radiological changes: erosion score (ES) absolute improvement -0.29% (95% CI -0.42% to -0.17%); NNTB of 6 (95% CI 4 to 10); MD -0.67 (95% CI -0.96 to -0.38); 714 participants, two studies (scale 0 to 230), but not a clinically important difference.-Serious adverse events (SAEs) were statistically but not clinically significantly more frequent for certolizumab pegol (200 mg every other week) with an absolute rate difference of 3% (95% CI 1% to 4%); number needed to treat for an additional harmful outcome (NNTH) of 33 (95% CI 25 to 100); Peto odds ratio (OR) 1.47 (95% CI 1.13 to 1.91); 3927 participants, nine studies.There was a clinically significant increase in all withdrawals in the placebo groups (for all doses and at all follow-ups) with an absolute rate difference of -29% (95% CI -16% to -42%), NNTH of 3 (95% CI 2 to 6), RR 0.47 (95% CI 0.39 to 0.56); and there was a clinically significant increase in withdrawals due to adverse events in the certolizumab groups (for all doses and at all follow-ups) with an absolute rate difference of 2% (95% CI 0% to 3%); NNTH of 58 (95% CI 28 to 329); Peto OR 1.45 (95% CI 1.09 to 1.94) 5236 participants Twelve studies.We judged the quality of evidence to be high for ACR50, DAS remission, SAEs and withdrawals due to adverse events, and moderate for HAQ and radiological changes, due to concerns about attrition bias. For all withdrawals we judged the quality of evidence to be moderate, due to inconsistency. AUTHORS' CONCLUSIONS: The results and conclusions did not change from the previous review. There is a moderate to high certainty of evidence from randomised controlled trials that certolizumab pegol, alone or combined with methotrexate, is beneficial in the treatment of RA for improved ACR50 and health-related quality of life, an increased chance of remission of RA, and reduced joint damage as seen on x-ray. Fewer people stopped taking their treatment, but most of these who did stopped due to serious adverse events. Adverse events were more frequent with active treatment. We found a clinically but not statistically significant risk of serious adverse events.

Recommendations for the evaluation and management of patients with rheumatic autoimmune and inflammatory diseases during the reproductive age, pregnancy, postpartum and breastfeeding. / Recomendaciones sobre actuaciones a seguir durante la edad fértil, el embarazo, posparto y lactancia en pacientes con enfermedades reumáticas inflamatorias y autoinmunes.

OBJECTIVE: To develop recommendations on the evaluation and management of patients with rheumatic autoimmune and inflammatory diseases during the reproductive age, pregnancy, post-partum and breastfeeding based on the best evidence and experience. METHODS: Recommendations were generated using nominal group and Delphi techniques. An expert panel of 12 rheumatologists was established. A systematic literature review and a narrative review (websites, clinical guidelines and other relevant documentation) were performed and presented to the panel in its 1st meeting to be discussed and to help define recommendations. A first draft of recommendations was generated and circulated for comments and wording refinement. A national survey analyzing different aspects of this topic was undertaken separately, followed by a Delphi process (2 rounds). Agreement with each recommendation was ranked on a scale of 1 (total disagreement) to 10 (total agreement), and was considered to be achieved if at least 70% voted≥7. The level of evidence and grade of recommendation were assessed using the Oxford Centre for Evidence-based Medicine Levels of Evidence. RESULTS: A total of 14 recommendations were generated for the preconception period (oral and hormonal contraception, reproductive techniques), pregnancy (planning, treatment and follow-up), and breastfeeding (treatment and follow-up). High-risk situations such as lupus or antiphospholipid syndrome were included. A consensus>90% was reached for all but one recommendation. CONCLUSIONS: These recommendations are intended to provide rheumatologists, patients, families and other stakeholders with a consensus on the evaluation and management of patients with autoimmune and inflammatory diseases during the reproductive age, pregnancy, postpartum and breastfeeding.

Characterization of Patients With Lupus Nephritis Included in a Large Cohort From the Spanish Society of Rheumatology Registry of Patients With Systemic Lupus Erythematosus (RELESSER).

The aim of the study was to profile those patients included in the RELESSER registry with histologically proven renal involvement in order to better understand the current state of lupus nephritis (LN) in Spain. RELESSER-TRANS is a multicenter cross-sectional registry with an analytical component. Information was collected from the medical records of patients with systemic lupus erythematosus who were followed at participating rheumatology units. A total of 359 variables including demographic data, clinical manifestations, disease activity, severity, comorbidities, LN outcome, treatments, and mortality were recorded. Only patients with a histological confirmation of LN were included. We performed a descriptive analysis, chi-square or Student's t tests according to the type of variable and its relationship with LN. Odds ratio and confidence intervals were calculated by using simple logistic regression. LN was histologically confirmed in 1092/3575 patients (30.5%). Most patients were female (85.7%), Caucasian (90.2%), and the mean age at LN diagnosis was 28.4 ±â€Š12.7 years. The risk for LN development was higher in men (M/F:47.85/30.91%, P < 0.001), in younger individuals (P < 0.001), and in Hispanics (P = 0.03). Complete response to treatment was achieved in 68.3% of patients; 10.35% developed ESRD, which required a kidney transplant in 45% of such cases. The older the patient, the greater was the likelihood of complete response (P < 0.001). Recurrences were associated with persistent lupus activity at the time of the last visit (P < 0.001) and with ESRD (P < 0.001). Thrombotic microangiopathy was a risk factor for ESRD (P = 0.04), as for the necessity of dialysis (P = 0.01) or renal transplantation (P = 0.03). LN itself was a poor prognostic risk factor of mortality (OR 2.4 [1.81-3.22], P < 0.001). Patients receiving antimalarials had a significantly lower risk of developing LN (P < 0.001) and ESRD (P < 0.001), and responded better to specific treatments for LN (P = 0.014). More than two-thirds of the patients with LN from a wide European cohort achieved a complete response to treatment. The presence of positive anti-Sm antibodies was associated with a higher frequency of LN and a decreased rate of complete response to treatment. The use of antimalarials reduced both the risk of developing renal disease and its severity, and contributed to attaining a complete renal response.