Prevalence and management of tuberculosis infection in Apulian rheumatologic patients treated with biologics: An observational cohort 10-year study from the BIOPURE registry.

INTRODUCTION: The objective of this study was to assess the 10-year prevalence of latent tuberculosis infection (LTBI) among Apulian patients with rheumatic diseases (RDs). Secondary endpoint was to record new cases of active TB disease and LTBI among patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs). METHODS: We analysed the results from the patients included in the BIOPURE registry from 2009 to 2018, who underwent QuantiFERON-TB Gold In-tube (QFT-GIT) test as screening before bDMARDs treatment. Demographic and clinical data were recorded at the time of the first QFT-GIT test. Administration of preventive therapy and bDMARD treatments were recorded for patients with positive QFT-GIT test. All new tuberculosis infections were recorded during the follow-up. RESULTS: The final study population included 3028 patients (855 rheumatoid arthritis, 1001 psoriatic arthritis, 833 spondyloarthritis, 130 connective tissue diseases, 33 systemic vasculitis and 176 other inflammatory rheumatic conditions), more frequently female (67.2%), with a mean age of 52 ± 18 years. Patients with QFT-GIT-positive test were elderly people, predominantly male with higher prevalence of diabetes as comorbidity. The 10-year prevalence of LTBI was 10.8%. Of note, no cases of TB reactivation were recorded in patients who completed preventive therapy treatment. Three thousand and sixteen patients were followed over time (42.6 ± 30 months), and five (.2%) developed active TB, which corresponds to .47 cases per 1000 person-years. CONCLUSIONS: In the 10-year observation, the use of bDMARDs seems to be safe in rheumatologic patients with positive QFT-GIT test treated according to current recommendations. Nevertheless, cases of primary TB disease did occur during treatment with biologicals.

1,25OH-Vitamin D3 and IL-17 Inhibition Modulate Pro-Fibrotic Cytokines Production in Peripheral Blood Mononuclear Cells of Patients with Systemic Sclerosis.

Objectives: IL-17 modulates the synthesis of several molecules involved in the pathogenesis of Systemic Sclerosis (SSc). Vitamin D (1,25(OH)2D3) shows anti-fibrotic properties and it is able to affect the IL-17 production in several experimental conditions. The aim of this study is to assess the production of IL-17A and pro-fibrotic cytokines in peripheral blood mononuclear cells (PBMCs) from subjects with SSc in basal conditions and after treatment with 1,25(OH)2D3 and IL-17A neutralizing antibodies. Methods: The production of IL-17A and pro-fibrotic cytokines (TGFß, CTGF and FGF2) in PBMCs obtained from 51 SSc patients and 31 healthy subjects was assessed both in basal conditions and in presence of anti-IL17A antibodies and several concentrations of 1,25(OH)2D3. The association of cytokines production with clinical disease characteristics and the in vitro effect of 1,25(OH)2D3 and IL-17A inhibition were assessed. Results: PBMCs from SSc subjects produced higher amount IL-17A, TGFß, CTGF and FGF2 compared to healthy controls. IL17, TGFß, CTGF and FGF2 levels were higher in SSc patients with interstitial lung disease and digital ulcers, whereas IL-17A production was lower in patients with PAH. IL- 17A inhibition reduced the production of FGF2, whereas enhanced the synthesis of TGFß and CTGF. 1,25(OH)2D3 decreased the production of IL17A and pro-fibrotic cytokines in a dose- dependent manner. Conclusions: IL-17A is involved in the regulation of fibrogenesis in SSc, and could represent an intriguing potential therapeutic target, even if its role remains controversial. 1,25(OH)2D3 inhibits both IL-17A and pro-fibrotic cytokines, confirming its potential anti-fibrotic effect.

Occurrence and predictive factors of high blood pressure, type 2 diabetes, and metabolic syndrome in rheumatoid arthritis: findings from a 3-year, multicentre, prospective, observational study.

OBJECTIVES: In rheumatoid arthritis (RA), "traditional" cardiovascular (CV) risk factors continue to be underdiagnosed and undertreated, thus increasing the risk of developing atherosclerosis. In this work, we evaluated the occurrence and predictive factors of "traditional" cardiovascular risk factors, with a focus on high blood pressure (HBP), type 2 diabetes (T2D), and metabolic syndrome (MetS), in participants with RA, in a 3-year, multicentre, prospective, observational study. METHODS: To assess the occurrence and predictive factors of HBP, T2D, and MetS, consecutive participants with RA, admitted to Italian Rheumatology Units, were evaluated in the GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) cohort, a 3-year, multicentre, prospective, observational study. RESULTS: In the present evaluation, 841 participants, who were fully followed up with 3-year of prospective follow-up were assessed. At the end of follow-up, a significant increased incidence of HBP, T2D, and MetS was recorded. Assessing predictive factors, the mean values of C-reactive protein during the follow-up were independent predictors of occurrence of those comorbidities, whereas participants maintaining remission showed a significant lower risk. Furthermore, therapy with hydroxychloroquine (HCQ) reduced the risk of occurrence of T2D and MetS. CONCLUSIONS: An increased incidence of HBP, T2D, and MetS was observed in assessed participants, prospectively followed-up. Furthermore, the analysis of predictive factors suggested that the rheumatoid pro-inflammatory process could increase the occurrence of these comorbidities. Conversely, metabolic and cardiovascular benefits of maintaining remission as well as of therapy with HCQ were reported.

The role of Interleukin-1 receptor antagonist as a treatment option in calcium pyrophosphate crystal deposition disease.

Calcium Pyrophosphate Crystal Deposition (CPPD) disease is characterized by the deposition of calcium pyrophosphate crystals in the cartilage. In most cases, it can manifest as a subclinical condition named chondrocalcinosis, often revealed by joint x-ray examination. In other cases, deposition can cause flares of arthritis, known as acute CPP crystal arthritis. In the last few years, many pathogenic pathways have been discovered. Interleukin-1 (IL-1) plays a key role in the pathogenesis of CPPD disease, both as a mediator of inflammatory response to crystals and as a promoter of damage to articular cartilage. In this review, we investigated the role of IL-1R inhibitor, such as Anakinra, as an alternative to the various therapeutic strategies for CPPD disease, especially among patients resistant to traditional treatment with NSAIDs, corticosteroids and colchicine.

Janus kinase inhibitors role in bone remodeling.

Janus kinases (JAKs) play a pleiotropic role in several important physiological processes, such as cell maturation, cell proliferation, and cell death, via providing transmission signals from several molecules, such as cytokines, interferons, hormones, and growth factors, to the nucleus. Bone physiology and remodeling are markedly influenced by proinflammatory cytokines. Among them, interleukin-1 (IL-1) and IL-6 are considered potent stimulator of bone resorption. Several cytokine receptors, such as IL-6 receptors, are characterized by tyrosine kinases of the JAK family associated with their intracellular domains. There is an emerging interest in the effects of JAKs inhibition on the cells involved in bone remodeling. JAK inhibitors represent a new class of molecules involved in the therapy of numerous immune-mediated inflammatory diseases. In this review, we want to focus on the role of JAKs inhibitors on bone remodeling and on RANKL-RANK-OPG signal and inflammatory cytokines which are involved in the regulation of bone cells, such as osteoblasts and osteoclasts.

Molecular Basis of Bone Aging.

A decline in bone mass leading to an increased fracture risk is a common feature of age-related bone changes. The mechanisms underlying bone senescence are very complex and implicate systemic and local factors and are the result of the combination of several changes occurring at the cellular, tissue and structural levels; they include alterations of bone cell differentiation and activity, oxidative stress, genetic damage and the altered responses of bone cells to various biological signals and to mechanical loading. The molecular mechanisms responsible for these changes remain greatly unclear and many data derived from in vitro or animal studies appear to be conflicting and heterogeneous, probably due to the different experimental approaches; nevertheless, understanding the main physio-pathological processes that cause bone senescence is essential for the development of new potential therapeutic options for treating age-related bone loss. This article reviews the current knowledge concerning the molecular mechanisms underlying the pathogenesis of age-related bone changes.

Osteoblast role in osteoarthritis pathogenesis.

Even if osteoarthritis pathogenesis is still poorly understood, numerous evidences suggest that osteoblasts dysregulation plays a key role in osteoarthritis pathogenesis. An abnormal expression of OPG and RANKL has been described in osteoarthritis osteoblasts, which is responsible for abnormal bone remodeling and decreased mineralization. Alterations in genes expression are involved in dysregulation of osteoblast function, bone remodeling, and mineralization, leading to osteoarthritis development. Moreover, osteoblasts produce numerous transcription factors, growth factors, and other proteic molecules which are involved in osteoarthritis pathogenesis.

Osteoblast Role in Rheumatic Diseases.

Alterations in osteoblast growth, differentiation and activity play a role in the pathogenesis of several rheumatic diseases, such as rheumatoid arthritis, spondyloarthritides, osteoarthritis, and osteoporosis. In fact, in these rheumatic diseases, abnormal activity of Wnt signaling, receptor activator of nuclear factor-κB (RANK)-RANK ligand (RANKL)-osteoprotegerin (OPG) signaling, bone morphogenetic proteins (BMPs) pathway and other mechanisms have been described in osteoblasts. This review article is focused on current knowledge on the role of osteoblast dysregulation occurring in rheumatic diseases.

Impact of biological therapy on spondyloarthritis.

PURPOSE: In this review, we focus on the clinical and radiological aspects related to the biological therapy of ankylosing spondylitis (AS), axial spondyloarthritis (SpA) and psoriatic arthritis (PsA). METHODS: A review was carried out in the main medical databases to evaluate the available literature. RESULTS: Even if there is emerging interest for the role of biological agents other than tumour necrosis factor (TNF)-α inhibitors in spondyloarthritis, anti-TNF-α treatment is currently the only effective therapy for patients in whom conventional therapy with non-steroideal anti-inflammatory drugs (NSAIDs) has failed. Nevertheless, the potential impact of earlier treatment and the best drugs or combinations of drugs for preventing radiographic progression in SpA are yet to be determined. CONCLUSIONS: Anti-TNF-α treatment is currently used with efficacy in the greater part of patients with SpA. In these patients, availability of biological treatment is limited on the bases of potential toxicity and cost. On the basis of clinical trials, biologics other than TNF-α inhibitors can currently not be recommended for the treatment of SpA.

Putative effects of potentially anti-angiogenic drugs in rheumatic diseases.

A role for angiogenesis has been described in several rheumatic diseases, including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, systemic sclerosis, systemic lupus erythematosus, vasculitides, and osteoarthritis, leading to the possibility that angiogenesis inhibition may be an additional useful therapeutic arm. While the role of anti-angiogenic therapy in rheumatoid arthritis has received attention, it is conceivable that the inhibition of pathological angiogenesis may also be a useful therapeutical approach in other rheumatic diseases. Numerous compounds, such as, for example, various interleukins, antibodies directed against angiogenic factors, peptides, estrogen metabolites, disease-modifying anti-rheumatic drugs, have been found to have anti-angiogenic properties. However, additional research is needed to obtain a clear understanding of the pathogenic mechanism of angiogenesis and the potential applications of anti-angiogenic therapy in rheumatic diseases.

Systemic effects of Wnt signaling.

Wnt signaling plays a key role in several physiological and pathological aspects. Even if Wnt signal was first described more than 20 years ago, its role in systemic effects, such as angiogenesis and vascular disorders, bone biology, autoimmune diseases, neurological diseases, and neoplastic disorders, was only recently emerged through the use of animal and in vitro models. Moreover, Wnt signaling inhibitors, such as DKK-1, may be advantageously considered targets for the treatment of several diseases, including osteoporosis, vascular diseases, inflammatory diseases, neurological diseases, and cancer. Nevertheless, further studies are required to provide a complete understanding of this complex signaling pathway, and especially of its role in human diseases, considering the possible advantageous effects of Wnt signaling inhibitors on the progression of disease conditions.

Bone effects of biologic drugs in rheumatoid arthritis.

Biologic agents used in the treatment of rheumatoid arthritis (RA) are able to reduce both disease activity and radiographic progression of joint disease. These drugs are directed against several proinflammatory cytokines (TNF α , IL-6, and IL-1) which are involved both in the pathogenesis of chronic inflammation and progression of joint structural damage and in systemic and local bone loss typically observed in RA. However, the role of biologic drugs in preventing bone loss in clinical practice has not yet clearly assessed. Many clinical studies showed a trend to a positive effect of biologic agents in preventing systemic bone loss observed in RA. Although the suppression of inflammation is the main goal in the treatment of RA and the anti-inflammatory effects of biologic drugs exert a positive effect on bone metabolism, the exact relationship between the prevention of bone loss and control of inflammation has not been clearly established, and if the available biologic drugs against TNF α , IL-1, and IL-6 can exert their effect on systemic and local bone loss also through a direct mechanism on bone cell metabolism is still to be clearly defined.

Bisphosphonates: effects on osteoblast.

PURPOSE: Bisphosphonates are synthetic analogues of pyrophosphate usually used in treating bone disorders such as osteoporosis, Paget's disease, fibrous dysplasia, hypercalcemia of malignancy, and inflammation-related bone loss. Though therapeutic effects of bisphosphonates depend primarily on their inhibitory effect on osteoclasts, increasing attention is being given to other effector cells, such as osteoblasts. This review focuses on the presumed effect of bisphosphonates on osteoblasts. METHODS: A review of the literature was conducted to evaluate the pharmacodynamic effects of bisphosphonates including inhibition of osteoclasts and apoptosis of osteocytes and osteoblasts as well as their potential stimulatory effects on the proliferation of osteoblasts. RESULTS: Studies have demonstrated that bisphosphonates may stimulate proliferation of osteoblasts and inhibit apoptosis of osteocytes and osteoblasts. CONCLUSION: Considering that osteoblasts may be involved in bone disorders, such as osteoporosis, osteopetrosis, osteogenesis imperfecta, and Paget's disease, and that bisphosphonates may stimulate proliferation of osteoblasts and inhibit apoptosis of osteocytes and osteoblasts, it is conceivable that a role for bisphosphonates exists in these diseases beyond merely the osteoclast influence.

HCV and Autoimmunity in Rheumatic Diseases.

HCV is a global health problem affecting mainly the liver and is often characterized by extrahepatic manifestations mediated by autoimmune reactions. Among these, arthritis and arthralgia are most frequent, as well as the presence of cryoglobulinemia that may induce vasculitis and sicca syndrome. Thus, HCV appears to be a trigger for an autoimmune response, as demonstrated by the finding of autoantibody in a high percentage of serum of these patients. Therefore, it is important that clinicians recognize these autoimmune manifestations as symptoms due to an autoimmune activity triggered by HCV in order to give the correct diagnosis and start an effective therapeutic strategy. Therefore, clinical examination, searching of markers of infection, as well as autoantibody patterns should be performed to make a correct differential diagnosis. The treatment should be based on antiviral drugs associated with immunosuppressive drugs according to autoimmune manifestations.

Rheumatological Diseases in HIV Infection.

A review of the available literature was performed in order to summarize the pathogenic and clinical connections between HIV infection and rheumatological syndromes. The increasing life expectancy during human immunodeficiency virus (HIV) infection has led to the observation of many rheumatological manifestations over the years in these types of patients. Although the pathological mechanisms are still not fully understood, several rheumatological diseases have been more commonly observed in the general population, especially after the advent of highly active antiretroviral therapy (HAART), and sometimes clinical and serological findings are influenced by the underlying condition which defines a characteristic onset or development of the disease. Autoimmune diseases occur during specific stages of the HIV infection, depending on the underlying pathogenic mechanism being mainly influenced by the CD4+ cells count. Several rheumatological diseases show peculiar clinical manifestations influenced by the underlying HIV infection leading to specific features less commonly observed in the healthy population. Conversely to pathological findings, broadly, HIV-1-neutralizing antibodies (BnAb) observed in several autoimmune diseases, such as SLE, could play a protective role in HIV infection. It is important to evaluate the onset of autoimmune diseases in HIV patients in order to start the appropriate treatment to avoid harmful events. More studies are needed to enlighten the trend of autoimmune diseases during HIV infection. Pathogenic mechanisms and clinical manifestations of rheumatological diseases during HIV infection are discussed in this review.

Adipokine role in physiopathology of inflammatory and degenerative musculoskeletal diseases.

We performed a systematic literature review to summarize the underlying pathogenic mechanisms by which adipokines influence rheumatological diseases and the resulting clinical manifestations. Increasing evidence display that numerous adipokines may significantly influence the development or clinical course of various rheumatological diseases. Despite the normal anti- or pro-inflammatory role of the cytokines, the serum level varies enormously in various rheumatological diseases. The expression of high levels of pro-inflammatory cytokines such as leptin or visfatin, respectively in systemic lupus erythematosus and in rheumatoid arthritis, represents a negative prognostic factor; other adipokines such as adiponectin, broadly known for their anti-inflammatory effects, showed a correlation with disease activity in rheumatoid arthritis. In the near future pro-inflammatory cytokines may represent a potential therapeutic target to restrain the severity of rheumatological diseases. Further studies on adipokines may provide important information on the pathogenesis of these diseases, which are not yet fully understood. The mechanisms by which adipokines induce, worsen, or suppress inflammatory and degenerative musculoskeletal pathologies and their clinical significance will be discussed in this review.

Influence of glucocorticoid treatment on trabecular bone score and bone remodeling regulators in early rheumatoid arthritis.

BACKGROUND: Glucocorticoids (GC) modulate several regulators involved in the pathogenesis of bone changes in rheumatoid arthritis (RA). Trabecular bone score (TBS) allows the indirect assessment of bone quality. The aim of this study was to investigate the effects of GC on TBS and serum levels of bone turnover regulators in patients with recent-onset RA. MATERIALS AND METHODS: Forty-seven subjects with recent-onset RA (< 6 months) were classified in two groups, low (lGC) and high (hGC) glucocorticoids, according to glucocorticoid dose regimens. Bone mineral density (BMD), TBS, and circulating Dickkopf-1 (Dkk1), sclerostin, osteoprotegerin (OPG), and RANK-L were evaluated at baseline and 6 and 12 months. RESULTS: BMD significantly declined after 12 months with no significant difference between the lGC and hGC group, whereas TBS decreased in the hGC group only. Circulating OPG decreased during the follow-up period, the reduction being significantly greater in hGC group; conversely, sclerostin and RANK-L serum increased, in a significantly greater extent in the hGC group. TBS inversely correlated with sclerostin, RANK-L, and Dkk1 circulating levels whereas directly correlated with OPG circulating levels. GC cumulative dose showed an inverse relationship with BMD in both the hGC and lGC groups; TBS values showed an inverse relationship with GC cumulative dose in the hGC group only. GC cumulative dose was associated to higher sclerostin and lower OPG serum levels. TBS did not correlate with disease activity whereas BMD was inversely related to disease activity. CONCLUSIONS: In early RA, GC exposure contributes to the reduction of BMD and affects bone quality depending on dose regimens. TBS could be a useful tool to evaluate the negative effect of GC on bone microarchitecture. TRIAL REGISTRATION: This study was ancillary to a parallel-group observational prospective study which was approved by the medical local ethics committee (protocol number DDG 334/19-06-2019).

Possible role of higher serum level of myoglobin as predictor of worse prognosis in Sars-Cov 2 hospitalized patients. A monocentric retrospective study.

BACKGROUND: Limited data on myoglobin and infectious diseases are available. In this study, we evaluate the potential role of myoglobin in predicting poor outcome in patients with Sars-Cov2 pneumonia. METHODS: One hundred and twenty-one Sars-Cov 2 patients with an average age of 69.9 ± 13.2 years, and symptoms duration of 8.8 ± 7.9 days were enrolled in the study. At the admission, the serum levels of myoglobin, erythrocyte sedimentation rate, C reactive protein (CRP), procalcitonin, ferritin, creatine phosphokinase, creatinine, fibrinogen, d-dimers, lactic dehydrogenase, troponin (Tn-I), creatine kinase myocardial band (CK-MB), complement fractions C3 and C4, immunoglobulins, interleukin 6 were evaluated. We also assessed the patients' complete clinical history and performed a thorough physical examination including age, disease history, and medications. RESULTS: Twenty-four (20%) patients died, and 18 (15%) patients required intensive care. The mean time between symptoms onset and death was 12.4 days ± 9.1. Univariate analysis of the patients' data highlighted some independent risk factors for mortality in COVID-19, including higher neutrophils rate (HR: 1.171), lower lymphocyte rate (HR: 0.798), high CK-MB serum levels (HR: 1.6), high Tn-I serum levels (HR: 1.03), high myoglobin serum levels (HR: 1.014), Alzheimer (HR 5.8), and higher CRP values (HR: 1.011). Cox regression analysis model revealed that higher serum values of myoglobin (HR 1.003; 95%CI: 1.001-1.006; p = 0.01), and CRP (HR 1.012; 95% CI: 1.001-1.023; p = 0.035) could be predictors of mortality in COVID-19 patients. The value of the myoglobin level for predicting 28 days-mortality using ROC curve was 121.8 ng/dL. Lower survival rate was observed in patients with serum levels of myoglobin>121.8 ng/dL (84% vs 20% respectively, p = 0.0001). CONCLUSION: Our results suggest that higher serum levels of myoglobin could be a considerable and effective predictor of poor outcomes in COVID-19 patients; a careful follow-up in these patients is strongly suggested. The possibility of enhancing these findings in other cohorts of COVID-19 patients could validate the clinical value of myoglobin as a biomarker for worse prognosis in COVID-19.

Preliminary Data on Post Market Safety Profiles of COVID 19 Vaccines in Rheumatic Diseases: Assessments on Various Vaccines in Use, Different Rheumatic Disease Subtypes, and Immunosuppressive Therapies: A Two-Centers Study.

An increased risk of developing severe infections has been evidenced in rheumatic disease (RD) patients, and anti-COVID-19 vaccination is strictly recommended for RD patients. However, up to now, no data are available on safety, immunogenicity and efficacy of COVID-19 vaccinations in RD patients. The possible development of adverse events (AEs), including the flare-up of underlying RD, represents a matter of growing importance. The aim of our study is to assess, in RD patients, the safety profile of different types of approved vaccines and the possible influence of immunosuppressive therapies and clinical or demographic characteristics of RD patients on development of AEs. Participants (n = 185; 30.7%) received anti-COVID-19 vaccinations, 137 with autoimmune/chronic inflammatory RD (Au/cIn-RD) and 48 with nonautoimmune/chronic inflammatory RD (no-Au/cIn-RD). AEs were recorded in 42% of patients after the first dose of vaccine, and in 26% of patients after the second dose. The most common reported AEs after anti-COVID 19 vaccines were site injection pain (17%), headache (12%), fever (12%), myalgia (10%) and fatigue (10%). Relapses of the underlying Au/c-In-RD were recorded in 2.2% of patients after the first dose of vaccine. In Au/c-In-RD the risk of developing AEs after the first dose of vaccine was lower in older patients (OR = 0.95; p = 0.001), and in the group of patients with complete control of RD (OR: 0.2; p = 0.010). A lower percentage of AEs was observed in patients with complete control of their Au/cIn-RD (29%) compared to those with low (57%) or moderate-high disease activity (63%) (p = 0.002 and p = 0.006 respectively). In this study all types of COVID-19 vaccines in use in Italy seemed safe in RD patients. The results of this study might provide reassuring information for Au/cIn RD patients and clinicians and could strengthen the data on vaccine safety to guide the use of COVID-19 vaccines in Au/cIn-RD on immunosuppressive agents.

Effectiveness of Certolizumab-Pegol in Rheumatoid Arthritis, Spondyloarthritis, and Psoriatic Arthritis Based on the BIOPURE Registry: Can Early Response Predict Late Outcomes?

BACKGROUND: Identification of predictors of clinical response to certolizumab-pegol (certolizumab) may aid the decision-making process for treating patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA). OBJECTIVE: The aim of our study was to evaluate the effectiveness of certolizumab and identify any predictors of favorable outcome in patients with RA, PsA, or SpA. METHODS: We studied 355 RA, SpA, and PsA patients starting treatment with certolizumab. Endpoints of the study were drug survival and identification of predictors of clinical outcome. Drug retention was analyzed via the Kaplan-Meier method, and hazard ratios (HRs) were estimated using Cox regression models. RESULTS: Of 355 certolizumab initiators, 178 had RA, 94 had PsA, and 83 had SpA. Biologic-naïve RA patients had significantly higher survival rates (73.3%) than switchers taking certolizumab as a second-line (49.0%) or third- or next-line biologic agent (51.2%; p = 0.0001). Instead, PsA and SpA patients showed similar drug retention rates regardless of the line of treatment. A significant clinical improvement from baseline was seen at 3 months for RA (28 joint-Disease Activity Score [DAS28]; p = 0.001), PsA (Disease Activity Index for PsA [DAPSA]; p = 0.001), and SpA (Bath Ankylosing Disease Index; p = 0.01). Biologic-naïve patients had the lowest HR (0.31; p = 0.001) of discontinuing certolizumab for RA, and the highest HR (7.94; p = 0.01) of achieving minimal disease activity (MDA) for PsA. For PsA, a predictor of late MDA was the achievement of low/remission DAPSA at 3 months, and 3-month low/remission DAS28 predicted late remission for RA. CONCLUSIONS: Our study revealed that the best predictor of certolizumab effectiveness in unselected patients with RA, PsA, or SpA was a biologic-naïve status and achievement of an early response within 3 months.