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ID PMID Title PublicationDate abstract
28300922 Paradoxical psoriasis after the use of anti-TNF in a patient with rheumatoid arthritis. 2016 Sep The use of tumor necrosis factor antagonists (anti-TNF) has become a usual practice to treat various inflammatory diseases. Although indicated for the treatment of psoriasis, anti-TNF may paradoxically trigger a psoriasiform condition. We present a case of a female patient who, during the use of infliximab for rheumatoid arthritis, developed psoriasis. In an attempt to switch anti-TNF class, we observed a cumulative worsening of the lesions requiring suspension of the immunobiological agent and the introduction of other drugs for clinical control. The therapeutic challenge of this paradoxical form of psoriasis is the focus of our discussion. The use of another anti-TNF in these patients is a matter of debate among experts.
26494588 Severe apoptotic enteropathy caused by methotrexate treatment for rheumatoid arthritis. 2016 Mar The folic acid antagonist methotrexate is a cornerstone treatment of rheumatoid arthritis. Its use is limited chiefly by gastrointestinal toxicity, which is among the main reasons for methotrexate discontinuation. Here, we report the case of a 40-year-old man on chronic methotrexate therapy in whom life-threatening apoptotic enteropathy with watery diarrhea and hypovolemic shock developed after he was switched from the oral to the intramuscular route, with no change in dosage. Colonic biopsies suggested drug-induced colitis, showing a nonspecific, mildly inflammatory infiltrate of lymphocytes and plasma cells, dilated damaged crypts, and a marked increase in basal crypt apoptosis (>20 apoptotic bodies/100 crypts). Clinicians should be aware that methotrexate can cause life-threatening apoptotic enteropathy. Increased basal crypt apoptosis in colonic biopsies with more than 5 apoptotic bodies/100 crypts should routinely suggest drug-induced enteropathy.
26424837 Biologic efficacy optimization--a step towards personalized medicine. 2016 May This following is a review of the factors that influence the outcome of biologic agents in the treatment of adult RA and, when synthesized into the clinical decision-making process, enhance optimization. Adiposity can exacerbate inflammatory diseases; patients with high BMI have worse outcomes from RA, including TNF inhibitors (TNFis), whereas the efficacy of abatacept and tocilizumab is unaffected. Smoking adversely affects TNFi outcomes but has less or no effect on the efficacy of rituximab and tocilizumab, and the effect on abatacept is unknown. Patients who are positive for ACPA and RF have better efficacy with rituximab and abatacept than those who are seronegative, whereas the influence of serotype is less significant for tocilizumab and more complex for TNFis. All biologics seem to do better when co-prescribed with MTX, whereas in monotherapy, tocilizumab is superior to adalimumab and prescription of a non-MTX DMARD has advantages over no DMARD for rituximab and adalimumab. Monitoring of TNFi drug levels is an exciting new field, correlating closely with efficacy in RA and PsA, and is influenced by BMI, adherence, co-prescribed DMARDs and anti-drug antibodies. The measurement of trough levels provides a potential tool for patients who are not doing well to determine early whether to switch within the TNFi class (if levels are low) or to a biologic with an alternative mode of action (if levels are normal or high). Conversely, the finding of supratherapeutic levels has the potential to enable individual patient selection for dose reduction without the risk of flare.
27992009 Development of exclusively cutaneous sarcoidosis in patient with rheumatoid arthritis duri 2016 Nov We report the case of a patient with rheumatoid arthritis who, after 2 months of treatment with etanercept, showed disseminated asymptomatic violaceous papules. Biopsy of the skin lesion showed chronic granulomatous dermatitis with negative staining for fungi and acid-fast bacilli (AFB). After discontinuation of etanercept, the patient's condition improved. Although apparently paradoxical, cases of cutaneous and systemic sarcoidosis after anti-TNF medications have been reported in the literature, with very few cases presenting exclusive cutaneous involvement.
26047709 Oral Squamous Cell Carcinoma Presenting in a Patient Receiving Adalimumab for Rheumatoid A 2015 Nov The efficacy of biologic agents in the treatment of inflammatory immune-mediated conditions has been clearly shown, but there also are numerous reports of adverse effects. Most reported adverse effects have been associated with tumor necrosis factor-α (TNF-α) inhibitors and include a possible increased risk of malignancy. There have been some reported cases of oral cancer developing in patients treated with TNF-α inhibitors. This case report describes a patient who was taking adalimumab for rheumatoid arthritis and who presented with a squamous cell carcinoma (SCC) in the mandible. Diagnosis was complicated because the clinical appearance was of a nonhealing extraction socket and the patient had a history of bisphosphonate therapy. An initial diagnosis of bisphosphonate-related osteonecrosis of the jaws was made, which delayed the commencement of appropriate treatment. This case highlights the importance of ruling out SCC in patients taking biological agents with unusual symptoms.
26607186 DADS neuropathy associated with anti-TNF-α therapy. 2015 Nov 25 A 52-year-old man with idiopathic Parkinson's disease and severe rheumatoid arthritis presented with a 1-year history of progressively worsening limb paraesthesia. Examination showed sensory loss in a glove and stocking distribution, absent reflexes and unsteady tandem gait. Nerve conduction studies suggested an acquired peripheral neuropathy with distal demyelination, which-together with the clinical phenotype-was consistent with a Distal Acquired Demyelinating Symmetric (DADS) neuropathy pattern. This was attributed to therapy with adalimumab, an antitumor necrosis factor (TNF)-α agent, which the patient had been taking for 2 years for rheumatoid arthritis. One month after discontinuing adalimumab, the limb paraesthesia had resolved completely and the patient had a normal tandem gait. Demyelinating disorders may rarely occur as complications of anti-TNF-α agents and therefore have implications for pretreatment counselling and ongoing monitoring. DADS neuropathy is a subtype of chronic inflammatory demyelinating polyradiculoneuropathy, which responds poorly to standard therapy and has not previously been described with anti-TNF-α therapy.
25534621 Periodontitis: from microbial immune subversion to systemic inflammation. 2015 Jan Periodontitis is a dysbiotic inflammatory disease with an adverse impact on systemic health. Recent studies have provided insights into the emergence and persistence of dysbiotic oral microbial communities that can mediate inflammatory pathology at local as well as distant sites. This Review discusses the mechanisms of microbial immune subversion that tip the balance from homeostasis to disease in oral or extra-oral sites.
26640276 Tetrandrine ameliorates collagen-induced arthritis in mice by restoring the balance betwee 2016 Feb 1 Tetrandrine is an alkaloid constituent of the root of Stephania tetrandra S. Moore. The long-term clinical uses of tetrandrine for treatments of rheumatalgia and arthralgia as well as the inhibition of rat adjuvant-induced arthritis imply that tetrandrine may have therapeutic potential in rheumatoid arthritis (RA). Here, we explored its anti-RA mechanism in collagen-induced arthritis (CIA) in relation to the balance between T helper (Th) 17 cells and regulatory T (Treg) cells. DBA/1 mice were immunized with chicken type II collagen and were orally administered tetrandrine for 14 consecutive days. Then, the mice were sacrificed, their joints were removed for histological analysis, and spleens and mesenteric lymph nodes (MLNs) were removed to examine the Th17 and Treg cells. Tetrandrine markedly alleviated the severity of arthritis, reduced the serum levels of pro-inflammatory cytokines, and restored the Th17/Treg balance, as demonstrated by the serum levels of their related cytokines (IL-17 and IL-10) and the proportion of each cell type. Tetrandrine inhibited Th17 cell differentiation and induced Treg cell differentiation in vitro . Notably, aryl hydrocarbon receptor (AhR) was proven to play a crucial role in tetrandrine-mediated T cell differentiation. The correlation between AhR activation, regulation of Th17/Treg and amelioration of arthritis by tetrandrine was verified in the CIA mice. Moreover, tetrandrine might be a ligand of AhR because it facilitated the expression of the AhR target gene cytochrome P450 1A1 (CYP1A1) and the activation of its downstream signaling pathways. Taken together, tetrandrine exerts its anti-arthritis efficacy by restoring Th17/Treg balance via AhR.
27840936 Effective treatment of polydatin weakens the symptoms of collagen-induced arthritis in mic 2016 Dec Polydatin is a natural extract used in traditional Chinese medicine, which leads to a marked improvement in the microcirculation perfusion and enhances the animal myocardial contraction force. The present study aimed to determine whether an effective treatment of polydatin ameliorates the symptoms of collagen‑induced arthritis (CIA), and also to explore the potential mechanism. Male DBA/1J mice were induced into CIA model mice. The administration of polydatin effectively suppressed CIA in mice. The serum levels of malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor‑α (TNF‑α) and interleukin 1β (IL‑1β) were effectively increased following the induction of CIA in the model mice compared with the control group. The elevated serum levels of MDA, SOD, TNF‑α and IL‑1β were markedly suppressed by the effective treatment of polydatin in CIA mice, compared with the CIA model group. However, an increase in the level of matrix metalloproteinase‑9 (MMP‑9) was markedly induced in the CIA mice compared with the control group. As compared with the CIA group, the expression of MMP‑9 was substantially reduced by the effective treatment of polydatin. Taken together, the effective treatment of polydatin ameliorated the symptoms of CIA through an exertion of its antioxidative and anti‑inflammatory effects, and also via activation of the expression of matrix metalloproteinase-9 (MMP-9) in mice.
27432105 Cytomegalovirus Reactivation Induced Acute Hepatitis and Gastric Erosions in a Patient wit 2016 Tocilizumab, an anti-human interleukin 6 receptor (IL-6R) monoclonal antibody, is widely used to treat rheumatoid arthritis (RA) and is expected to exhibit clinical efficacy when used to treat other autoimmune diseases. However, a risk of opportunistic infection is occasionally recognized. A 54-year-old woman had received an oral corticosteroid and methotrexate to treat RA. Despite receiving these treatments, she received additional treatment with tocilizumab due to poor control of the disease activity. She presented at our hospital with a high fever and epigastralgia 19 days after receiving this treatment. A laboratory evaluation revealed liver injury and cytomegalovirus (CMV) viremia. Abdominal ultrasonography and computed tomography (CT) revealed hepatosplenomegaly, but no ascites. Upper gastrointestinal endoscopy revealed gastric erosions induced by CMV, which were confirmed immunohistochemically. Hence, we diagnosed the patient with CMV reactivation-induced acute hepatitis and gastric erosions under tocilizumab treatment. She received an anti-cytomegalovirus drug, ganciclovir, for 14 days due to her viremia and impaired general condition, which was suggestive of a severe infection. Her general condition subsequently improved, the liver function test results normalized, and the gastric erosions disappeared. In conclusion, although tocilizumab is very useful for treating certain autoimmune and inflammatory diseases, and will be prescribed more widely in the future, associated CMV infections must be closely monitored, as these can be lethal.
25344777 The descriptive epidemiology of rheumatoid arthritis in Catalonia: a retrospective study u 2016 Mar Information on the epidemiology of rheumatoid arthritis (RA) in Southern Europe is scarce. We estimated the age- and gender-adjusted incidence and prevalence of RA in Catalonia using routinely collected primary care records. We identified incident (2009-2012) and prevalent (on 31 December 2012) cases of RA in the SIDIAP database using ICD-10 codes. SIDIAP contains anonymized data from computerized primary care records for about five million adults (>80 % of the population). We estimated age- (5-year groups) and gender-specific, and directly standardized incidence and prevalence of RA and confidence intervals (95% CIs) assuming a Poisson distribution. A total of 20,091 prevalent (among whom 5,796 incident) cases of RA were identified among 4,796,498 study participants observed for up to 4 years. Rates of RA increased with age in both genders, peaking at the age of 65-70 years. Age- and gender-standardized incidence and prevalence rates were 0.20/1,000 person-years (95% CI 0.19-0.20) and 4.17/1,000 (4.11-4.23) respectively. Rheumatoid factor was positive (≥10 IU/mL) in 1,833 (73.9 %) of 2,482 cases tested in primary care. The incidence and prevalence of RA in Catalonia are similar to those of other Southern European regions, and lower than those of northern areas. This data will inform health care planning and resource allocation.
25524318 Cemented metal-on-metal total hip replacement with 28-mm head: prospective, long-term, cli 2015 May PURPOSE: The aim of this study was to evaluate the long-term clinical, radiological and metal ion blood concentration results following 28-mm metal-on-metal cemented total hip replacement using Metasul(®) acetabular component and polished, cannulated Allopro CF-30 (Sulzer-Medica, subsequently Centerpulse-Zimmer, Winterthur, Switzerland) femoral component. METHODS: Prospective follow-up of patients operated between 1997 and 2000 at a district general hospital. RESULTS: Seventy-nine patients (89 implants) with female predominance and median age of 66 years (IQR 45-87 years) were prospectively followed up for mean 13 years (11-14 years). There was significant improvement in Harris hip score (paired Student's t test p = 0.0001). The mean plasma cobalt and chromium levels were 1.3 µg/L (IQR 0.5-23.9) and 3.6 µg/L (IQR 1.0-22), respectively. Elevated plasma metal ions >7 µg/L were noted in four asymptomatic patients with negative ultrasound examination. Radiolucent lines were present in various zones but majority were stable. One femoral component was revised due to aseptic femoral loosening. Three acetabular and one femoral component have radiologically failed but not revised yet. The Kaplan-Meier survival at 14 years was 92 % for failure as endpoint. CONCLUSION: The long-term survival of Metasul(®) cemented total hip replacements using 28-mm metal-on-metal head is comparable with metal on polyethylene bearing devices.
27303036 Conserved 33-kb haplotype in the MHC class III region regulates chronic arthritis. 2016 Jun 28 Genome-wide association studies have revealed many genetic loci associated with complex autoimmune diseases. In rheumatoid arthritis (RA), the MHC gene HLA-DRB1 is the strongest candidate predicting disease development. It has been suggested that other immune-regulating genes in the MHC contribute to the disease risk, but this contribution has been difficult to show because of the strong linkage disequilibrium within the MHC. We isolated genomic regions in the form of congenic fragments in rats to test whether there are additional susceptibility loci in the MHC. By both congenic mapping in inbred strains and SNP typing in wild rats, we identified a conserved, 33-kb large haplotype Ltab-Ncr3 in the MHC-III region, which regulates the onset, severity, and chronicity of arthritis. The Ltab-Ncr3 haplotype consists of five polymorphic immunoregulatory genes: Lta (lymphotoxin-α), Tnf, Ltb (lymphotoxin-β), Lst1 (leukocyte-specific transcript 1), and Ncr3 (natural cytotoxicity-triggering receptor 3). Significant correlation in the expression of the Ltab-Ncr3 genes suggests that interaction of these genes may be important in keeping these genes clustered together as a conserved haplotype. We studied the arthritis association and the spliceo-transcriptome of four different Ltab-Ncr3 haplotypes and showed that higher Ltb and Ncr3 expression, lower Lst1 expression, and the expression of a shorter splice variant of Lst1 correlate with reduced arthritis severity in rats. Interestingly, patients with mild RA also showed higher NCR3 expression and lower LST1 expression than patients with severe RA. These data demonstrate the importance of a conserved haplotype in the regulation of complex diseases such as arthritis.
25303306 Combined inhibition of tumor necrosis factor α and interleukin-17 as a therapeutic opport 2015 Jan OBJECTIVE: Rheumatoid arthritis therapies that are based on inhibition of a single cytokine, e.g., tumor necrosis factor α (TNFα) or interleukin-6 (IL-6), produce clinically meaningful responses in only about half of the treated patients. This study was undertaken to investigate whether combined inhibition of TNFα and IL-17 has additive or synergistic effects in the suppression of mesenchymal cell activation in vitro and inflammation and tissue destruction in arthritis in vivo. METHODS: Cultures of human fibroblast-like synoviocytes (FLS) were stimulated with TNFα, IL-17, or a combination of both. Single/combined neutralizing antibodies against TNFα and IL-17 were used to examine in vitro cytokine responses and in vivo development of arthritis and bone and cartilage destruction in TNFα-transgenic mice. Bispecific anti-TNFα/IL-17 antibodies were designed, and their potential to block cytokine responses in human FLS was tested. RESULTS: TNFα and IL-17 had additive/synergistic effects in promoting production of IL-6, IL-8, and granulocyte colony-stimulating factor, as well as matrix metalloproteinases, in FLS. Bispecific anti-TNFα/IL-17 antibodies showed superior efficacy in blocking cytokine and chemokine responses in vitro. Furthermore, dual versus single inhibition of both cytokines using neutralizing antibodies was more effective in inhibiting the development of inflammation and bone and cartilage destruction in arthritic mice. CONCLUSION: Combined blockade of TNFα and IL-17 was more effective than single blockade in inhibiting cytokine, chemokine, and matrix enzyme responses from human mesenchymal cells and in blocking tissue destruction associated with arthritis, and additionally showed a positive impact on rebalance of bone homeostasis. Bispecific anti-TNFα/IL-17 antibodies may have superior efficacy in the treatment of arthritis and may overcome the limited therapeutic responses obtained with single cytokine neutralization.
26562235 High-Resolution US of Rheumatologic Diseases. 2015 Nov For the past 15 years, high-resolution ultrasonography (US) is being routinely and increasingly used for initial evaluation and treatment follow-up of rheumatologic diseases. This imaging technique is performed by using high-frequency linear transducers and has proved to be a powerful diagnostic tool in evaluation of articular erosions, simple and complex joint and bursal effusions, tendon sheath effusions, and synovitis, with results comparable to those of magnetic resonance imaging, excluding detection of bone marrow edema. Crystal deposition diseases including gouty arthropathy and calcium pyrophosphate deposition disease (CPPD) have characteristic appearances at US, enabling differentiation between these two diseases and from inflammatory arthropathies. Enthesopathy, which frequently accompanies psoriatic and reactive arthritis, also has a characteristic appearance at high-resolution US, distinguishing these two entities from other inflammatory and metabolic arthropathies. The presence of Doppler signal in examined joints, bursae, and tendon sheaths indicates active synovitis. Microbubble echo contrast agents augment detection of tissue vascularity and may act in the future as a drug delivery vehicle. Frequently, joint, tendon sheath, and bursal fluid aspirations and therapeutic injections are performed under US guidance. The authors describe the high-resolution US technique including gray-scale, color or power Doppler, and contrast agent-enhanced US that is used in evaluation of rheumatologic diseases of the wrist and hand and the ankle and foot in their routine clinical practice. This article demonstrates imaging findings of normal joints, rheumatoid arthritis, gouty arthritis, CPPD, psoriatic and reactive arthritis, and osteoarthritis.
27268854 A review of the methods used to define glucocorticoid exposure and risk attribution when i 2016 Sep BACKGROUND: Glucocorticoid therapy is used widely in patients with rheumatoid arthritis (RA) with good efficacy but concerns about safety including fractures. Estimates of fracture risk for any given patient are complicated by the dynamic pattern of glucocorticoid use, where patients vary in their dose, duration and timing of glucocorticoid use. OBJECTIVE: To investigate which methods are currently used to attribute fractures to glucocorticoid exposure and investigate whether such methods can consider individual treatment patterns. RESULTS: Thirty-eight studies used five common definitions of risk attribution to glucocorticoid exposure: "current use", "ever use", "daily dose", "cumulative dose" and "time variant". One study attempted to combine multiple definitions where "cumulative dose" was nested within "daily dose", covering the effects of dose and duration but not timing. The majority of results demonstrated an equivocal or increased risk of fracture with increased exposure, although there was wide variation, with odds ratios, hazard ratios and relative risks ranging from 0.16 to 8.16. Within definitions there was also variability in the results with the smallest range for "time variant", 1.07 to 2.8, and the largest for "cumulative dose", ranging from risk estimates of 0.88 to 8.12. CONCLUSION: Many studies have looked into the effect of glucocorticoids on fracture risk in patients with RA. Despite this, there is no clear consensus about the magnitude of risk. This is a consequence of the varied analysis models and their different assumptions. Moreover, no current analysis method allows consideration of dose, duration and timing of glucocorticoid therapy, preventing a clear understanding of fracture risk for patients and their individual treatment patterns.
24249811 B cell resistance to Fas-mediated apoptosis contributes to their ineffective control by re 2015 Jan OBJECTIVE: To investigate whether regulatory T cells (Treg) can control B cell function in rheumatoid arthritis (RA) and if not to explore the basis for this defect. METHODS: Suppression of B cell responses by Treg was analysed in vitro by flow cytometry and ELISA using peripheral blood mononuclear cells from 65 patients with RA and 41 sex-matched and aged-matched healthy volunteers. Blocking and agonistic antibodies were used to define the role of Fas-mediated apoptosis in B cell regulation. RESULTS: Treg failed to restrain B cell activation, proinflammatory cytokine and antibody production in the presence of responder T cells in RA patients. This lack of suppression was not only caused by impaired Treg function but was also due to B cell resistance to regulation. In healthy donors, control by Treg was associated with increased B cell death and relied upon Fas-mediated apoptosis. In contrast, RA B cells had reduced Fas expression compared with their healthy counterparts and were resistant to Fas-mediated apoptosis. CONCLUSIONS: These studies demonstrate that Treg are unable to limit B cell responses in RA. This appears to be primarily due to B cell resistance to suppression, but Treg defects also contribute to this failure of regulation. Our data identify the Fas pathway as a novel target for Treg-mediated suppression of B cells and highlight a potential therapeutic approach to restore control of B cells by Treg in RA patients.
26510317 Enhancing Methotrexate Tolerance with Folate Tagged Liposomes in Arthritic Mice. 2015 Dec Methotrexate is the first line of treatment of rheumatoid arthritis. Since many patients become unresponsive to methotrexate treatment, only very expensive biological therapies are effective and increased methotrexate tolerance strategies need to be identified. Here we propose the encapsulation of methotrexate in a new liposomal formulation using a hydrophobic fragment of surfactant protein conjugated to a linker and folate to enhance their tolerance and efficacy. In this study we aim to evaluate the efficiency of this system to treat rheumatoid arthritis, by targeting folate receptor β present at the surface of activated macrophages, key effector cells in this pathology. The specificity of our liposomal formulation to target folate receptor β was investigated both in vitro as in vivo using a mouse model of arthritis (collagen-induced arthritis in DBA/1J mice strain). In both systems, the liposomal constructs were shown to be highly specific and efficient in targeting folate receptor β. These liposomal formulations also significantly increase the clinical benefit of the encapsulated methotrexate in vivo in arthritic mice, together with reduced expression of CD39 and CD73 ectonucleotidases by joint-infiltrating macrophages. Thus, our formulation might be a promising cost effective way to treat rheumatoid arthritis and delay or reduce methotrexate intolerance.
24528544 Endogenous pain modulation in response to exercise in patients with rheumatoid arthritis, 2015 Feb OBJECTIVE: Temporal summation (TS) of pain, conditioned pain modulation (CPM), and exercise-induced analgesia (EIA) are often investigated in chronic pain populations as an indicator for enhanced pain facilitation and impaired endogenous pain inhibition, respectively, but interactions are not yet clear both in healthy controls and in chronic pain patients. Therefore, the present double-blind randomized placebo-controlled study evaluates pains cores, TS, and CPM in response to exercise in healthy controls, patients with chronic fatigue syndrome and comorbid fibromyalgia (CFS/FM), and patients with rheumatoid arthritis (RA), both under placebo and paracetamol condition. METHODS: Fifty-three female volunteers - of which 19 patients with CFS/FM, 16 patients with RA, and 18 healthy controls - underwent a submaximal exercise test on a bicycle ergometer on 2 different occasions (paracetamol vs. placebo), with an interval of 7 days. Before and after exercise, participants rated pain intensity during TS and CPM. RESULTS: Patients with rheumatoid arthritis showed decreased TS after exercise, both after paracetamol and placebo (P < 0.05). In patients with CFS/FM, results were less univocal. A nonsignificant decrease in TS was only observed after taking paracetamol. CPM responses to exercise are inconclusive, but seem to worsen after exercise. No adverse effects were seen. CONCLUSION: This study evaluates pain scores, TS, and CPM in response to submaximal exercise in 2 different chronic pain populations and healthy controls. In patients with RA, exercise had positive effects on TS, suggesting normal EIA. In patients with CFS/FM, these positive effects were only observed after paracetamol and results were inconsistent.
27987002 Gender-associated comorbidities in rheumatoid arthritis and their impact on outcome: data 2017 Apr GENIRA [Gender in Rheumatoid Arthritis (RA)] is a comprehensive project aimed at studying gender differences in RA patients and how these differences impact on these patient outcomes. We are now reporting such data. Seventy RA patients of each gender were cross-sectionally evaluated following a preestablished protocol. Univariate and multivariate analyses focused in the different gender-associated comorbidity profiles and how they impact in the quality of life and disability of RA patients as assessed by the SF-36 and the Modified Health Assessment Questionnaire (M-HAQ), respectively. Both groups were comparable regarding their main demographic and clinical features. Different comorbidity profiles were found in both genders, with higher frequencies of diabetes mellitus, peptic ulcer, ischemic heart disease, smoking and chronic obstructive pulmonary disease among men and of depression and osteoporosis among women. The M-HAQ was lower in women than in men (0.89 ± 2.6 vs 0.22 ± 0.9, p = 0.04) as there were some sub-scales of the SF-36 [mental health (63.7 ± 22.0 vs 71.8 ± 21.1; p = 0.02), general health (41.3 ± 21.7 vs 50.0 ± 24.3; p = 0.02), physical functioning (PF) (57.7 ± 22.1 vs 67.3 ± 22.7; p = 0.01) and the physical summary component (PSC) (39.3 ± 8.9 vs 42.4 ± 9.3, p = 0.04)]. Multivariate analysis indicated the independent association between depression and osteoporosis rather than gender with the M-HAQ, PSC and PF and of only depression with the MH and GH. Women with RA present significantly worse disability and QOL outcomes than men; these differences can be explained by female gender-associated comorbidities such as depression and osteoporosis rather than gender per se.