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ID PMID Title PublicationDate abstract
22170479 Brief report: a phase IIa, randomized, double-blind, placebo-controlled trial of apilimod 2012 Jun OBJECTIVE: To investigate the safety, tolerability, pharmacokinetics, and efficacy of apilimod mesylate, an oral interleukin-12 (IL-12)/IL-23 inhibitor, in patients with rheumatoid arthritis (RA). METHODS: We performed a phase IIa, randomized, double-blind, placebo-controlled proof-of-concept study of apilimod, in combination with methotrexate, in 29 patients with active RA (3:1 ratio of apilimod-treated to placebo-treated patients) in 3 stages. Patients received apilimod 100 mg/day or placebo for 4 weeks (stage 1) or 8 weeks (stage 2). In stage 3, patients received apilimod 100 mg twice a day or placebo for 8 weeks, with an optional extension of 4 weeks. Clinical response (Disease Activity Score in 28 joints [DAS28] and American College of Rheumatology [ACR] criteria) was assessed throughout; synovial tissue samples collected at baseline and on day 29 (stages 1 and 2) or day 57 (stage 3) were stained for cellular markers and cytokines for immunohistochemistry analysis. RESULTS: While only mild adverse events were observed in stages 1 and 2, in stage 3, all patients experienced headache and/or nausea. Among apilimod-treated patients (100 mg/day), there was a small, but significant, reduction in the DAS28 on day 29 and day 57 compared with baseline. ACR20 response was reached in only 6% of patients on day 29 and 25% of patients on day 57, similar to the percentage of responders in the placebo group. Increasing the dosage (100 mg twice a day) did not improve clinical efficacy. Consistent with clinical results, apilimod did not have an effect on expression of synovial biomarkers. Of importance, we also did not observe an effect of apilimod on synovial IL-12 and IL-23 expression. CONCLUSION: Our results do not support the notion that IL-12/IL-23 inhibition by apilimod is able to induce robust clinical improvement in RA.
22679301 Induction therapy with a combination of DMARDs is better than methotrexate monotherapy: fi 2013 Jan OBJECTIVE: To determine the most effective induction disease-modifying antirheumatic drug (DMARD) strategy in early rheumatoid arthritis (RA), second to compare one single dose of intramuscular glucocorticoids (GCs) with daily oral GCs during the induction phase. METHODS: The 3-month data of a single-blinded clinical trial in patients with recent-onset arthritis (tREACH) were used. Patients were included who had a high probability (>70%) of progressing to persistent arthritis, based on the prediction model of Visser. Patients were randomised into three induction therapy strategies: (A) combination therapy (methotrexate (MTX) + sulfasalazine + hydroxychloroquine) with GCs intramuscularly; (B) combination therapy with an oral GC tapering scheme and (C) MTX with oral GCs similar to B. A total of 281 patients were randomly assigned to strategy (A) (n=91), (B) (n=93) or (C) (n=97). RESULTS: The Disease Activity Score (DAS) after 3 months was lower in patients receiving initial combination therapy than in those receiving MTX monotherapy (0.39 (0.67 to 0.11, 95% CI)). DAS did not differ between the different GC bridging treatments. After 3 months 50% fewer biological agents were prescribed in the combination therapy groups. Although the proportion of patients with medication adjustments differed significantly between the treatment arms, no differences were seen in these adjustments due to adverse events after stratification for drug. CONCLUSION: Triple DMARD induction therapy is better than MTX monotherapy in early RA. Furthermore, no differences were seen in medication adjustments due to adverse events after stratification for drug. Intramuscular and oral GCs are equally effective as bridging treatments and both can be used.
21881327 Adalimumab-associated pulmonary cryptococcosis. 2011 This is the first report of adalimumab-associated pulmonary cryptococcosis. A 56-year-old female with rheumatoid arthritis without a history of pulmonary disease was simultaneously administered adalimumab (40 mg/2 wks), methotrexate (4 mg/wk), and isoniazid (200 mg/day). Five months later, chest radiography revealed a small spiculated pulmonary nodule, and the laboratory test results, including levels of tumor markers and plasma β-D-glucan, were within normal ranges. Since the lesion continued to grow, even after discontinuing adalimumab, it was surgically resected. Grocott staining of the tissue sample revealed black-brown fungi, identified as Cryptococcus neoformans in culture. The patient now remains well, without adalimumab therapy.
21859685 Ofatumumab, a fully human anti-CD20 monoclonal antibody, in biological-naive, rheumatoid a 2011 Dec OBJECTIVES: To evaluate the efficacy and safety of intravenous ofatumumab, a fully human anti-CD20 monoclonal antibody, in biological-naive, active rheumatoid arthritis (RA) patients despite methotrexate treatment. METHODS: In this double-blind, placebo-controlled, phase III study, active RA patients on stable methotrexate were randomly assigned to one course of two infusions of ofatumumab 700 mg (n=130) or placebo (n=130), 2 weeks apart. The primary endpoint was the ACR20 response at week 24. Secondary endpoints included ACR50/70, EULAR response, disease activity score based on 28 joints using C-reactive protein, adverse events (AE) and immunogenicity. RESULTS: At week 24, a greater proportion of patients on ofatumumab compared with placebo achieved an ACR20 response (50% vs 27%, p<0.001) and a good or moderate EULAR response (67% vs 41%, p<0.001). All other key secondary efficacy endpoints were significantly improved on ofatumumab. Efficacy observed by 8 weeks was sustained throughout the study. The most common AE for ofatumumab versus placebo were rash (21% vs <1%) and urticaria (12% vs <1%), mostly occurring on the first infusion day. Overall, first-dose infusion reactions were 68% for ofatumumab and 6% for placebo, mostly mild to moderate; second-dose infusion reactions markedly declined (<1% and 0%). Serious AE were reported in 5% of ofatumumab versus 3% of placebo patients. Infection rates were 32% and 26% (serious infections <1% and 2%), respectively. One death (interstitial lung disease), unrelated to study drug, was reported on ofatumumab. No antidrug antibodies were detected in ofatumumab patients. CONCLUSIONS: Ofatumumab significantly improved all clinical outcomes in biological-naive, active RA patients with no detectable immunogenicity at week 24. No unexpected safety findings were identified. Trial Registry clinical trials.gov registration number NCT00611455.
21972242 Effectiveness of disease-modifying antirheumatic drug co-therapy with methotrexate and lef 2012 Mar OBJECTIVES: To compare the effectiveness and safety of rituximab alone or in combination with either methotrexate or leflunomide. METHODS: 10 European registries submitted anonymised datasets with baseline, 3, 6, 9 and 12-month clinical data from patients who started rituximab. RESULTS: 1195 patients were treated with rituximab plus methotrexate, 177 with rituximab plus leflunomide and 505 with rituximab alone. Significantly more patients achieved a European League Against Rheumatism good response at 6 months when treated with rituximab plus leflunomide (29.1%) compared with rituximab plus methotrexate (21.1%) and rituximab alone (19.3%; p=0.02 and p=0.01, respectively). Similar results were observed at 12 months. Adverse events occurred in 10.2%, 13.2% and 13.9% of patients on rituximab plus leflunomide, rituximab plus methotrexate and rituximab alone, respectively. CONCLUSIONS: Leflunomide is an effective and safe alternative to methotrexate as concomitant treatment with rituximab. Slightly better results were obtained by the combination of rituximab and leflunomide than rituximab and methotrexate, raising the possibility of a synergistic effect of leflunomide and rituximab.
21362765 Association of anti-modified citrullinated vimentin with subclinical atherosclerosis in ea 2011 May OBJECTIVE: To investigate anti-modified citrullinated vimentin (anti-MCV) in early rheumatoid arthritis (RA), including correlation with disease activity and cardiovascular risk factors, compared with anti-cyclic citrullinated peptides (anti-CCP3). METHODS: Anti-MCV and anti-CCP3 concentrations were measured in 100 patients with early RA and 100 healthy controls at baseline to determine sensitivity and specificity. Patients received methotrexate (MTX) 0.2 mg/kg/week plus prednisone 10 mg/day. Anti-MCV, anti-CCP3, rheumatoid factor (RF), Disease Activity Score for 28 joints (DAS-28), lipid profile, erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein assay (hsCRP), homeostasis model assessment for insulin resistance (HOMA-IR) index, tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and carotid intima-media thickness (cIMT) were measured before and after 12 months of treatment. RESULTS: The sensitivity and specificity for anti-MCV antibody were 75% and 90%, respectively, and for anti-CCP3 antibody 71% and 96%. Serum anti-MCV and serum anti-CCP3 levels at baseline were positively correlated with hsCRP, IL-6, HOMA-IR index, serum RF levels (p < 0.001), and cIMT (p < 0.05). Serum anti-MCV was positively correlated with serum anti-CCP3 levels. There were significant positive correlations between the percentage of changes of anti-MCV levels versus changes in DAS-28, ESR, hsCRP, atherogenic ratios (TC/HDL-C and LDL-C/HDL-C), apolipoprotein A-I, IL-6, TNF-α, HOMA-IR index, and cIMT. These correlations were not found between changes in anti-CCP3 levels compared to clinical, laboratory, and radiological variables. CONCLUSION: Anti-MCV was as sensitive as anti-CCP3 in diagnosing early RA. Anti-MCV testing appears to be useful for monitoring associated subclinical atherosclerosis in early RA.
21736751 Efficacy and safety of the human anti-IL-1β monoclonal antibody canakinumab in rheumatoid 2011 Jul 7 BACKGROUND: Canakinumab is a fully human anti-interleukin IL-1beta monoclonal antibody, being investigated for the treatment of rheumatoid arthritis (RA). This multicenter, phase II, randomized, double-blind, placebo-controlled, parallel-group, dose-finding study investigated the efficacy and safety of canakinumab in patients with active RA despite ongoing therapy at stable doses of methotrexate. METHODS: Patients were randomized to receive one of four regimens, in addition to methotrexate, for 12 weeks: canakinumab 150 mg subcutaneously (SC) every 4 weeks (q4wk), canakinumab 300 mg SC (2 injections of 150 mg SC) every 2 weeks, a 600 mg intravenous loading dose of canakinumab followed by 300 mg SC every 2 weeks', or placebo SC every 2 weeks. RESULTS: Among 274 patients with evaluable efficacy data, the percentage of responders according to American College of Rheumatology 50 criteria (the primary endpoint, based on a 28-joint count) was significantly higher with canakinumab 150 mg SC q4wk than with placebo (26.5% vs. 11.4%, respectively; p = 0.028). Compared to placebo, this dosage of canakinumab was also associated with significantly more favorable responses at week 12 with respect to secondary endpoints including the Disease Activity Score 28, scores on the Health Assessment Questionnaire and Functional Assessment of Chronic Illness Therapy-Fatigue, swollen 28-joint count, and patient's and physician's global assessments of disease activity. No safety concerns were raised with canakinumab therapy, particularly with regard to infections. Few injection-site reactions occurred. CONCLUSION: The addition of canakinumab 150 mg SC q4wk improves therapeutic responses among patients who have active RA despite stable treatment with methotrexate. TRIAL REGISTRATION: (ClinicalTrials.gov identifier: NCT00784628).
21161534 Causes of DMARD withdrawal following ADR within 6 months of initiation among Indian rheuma 2012 Mar The present study was conducted in Indian rheumatoid arthritis (RA) patients prescribed disease-modifying anti-rheumatic drugs (DMARDs) to determine the incidence and type of adverse drug reactions (ADRs) leading to their withdrawal in the initial 6 months of therapy. This was considered important as pharmacogenetic variations in the pattern of RA in different populations and genetic differences in efficacy and safety to drugs demand separate studies to be conducted in different populations. Hospital records were used to identify 1,000 consecutive patients with RA fulfilling the American College of Rheumatology criteria and having at least 6-month follow-up. Age, gender, duration of arthritis, drug usage and ADR-related drug withdrawal were recorded from the charts. Most of the patients were put on single DMARD. Combined use of DMARD was less frequent and non-use of DMARD was common; however, disease control was good. The commonest DMARD used in our hospital was hydroxychloroquine 444 (44%) and the commonest combination used was methotrexate with hydroxychloroquine by 55 (6%). Sulphasalazine use showed preference to young and males. Supportive drugs used were NSAIDs by 883 (88%), corticosteroids by 646 (65%), paracetamol by 594 (59%) and amitriptyline by 88 (9%). Incidence of ADR-related DMARD withdrawal was maximum with leflunomide 2/15 (13.33%) followed by methotrexate 9/116 (7.76%), sulphasalazine 6/185 (3.24%), chloroquine 3/131 (2.29%) and hydroxychloroquine 8/444 (1.8%). Severity and symptomatology of disease, genetic pattern of patients, financial status, previous experience of the clinicians and patients, availability of drugs, patient expectations and compliance were the main factors that lead to a difference in pattern of therapy in our patients compared to other population.
22041430 [Pneumocystis pneumonia developed in two patients with rheumatoid arthritis during treatme 2011 While tumor necrosis factor (TNF) inhibitors have dramatically improved the clinical outcomes of rheumatoid arthritis (RA) in recent years, infectious complications are a serious concern. Adalimumab (ADA) is a newly-developed human monoclonal antibody against TNF-alpha. Here we report 2 cases of pneumocystis pneumonia (PCP) which developed in RA patients during ADA therapy. One patient is a 66-year-old woman who had a history of RA for 6 months. The patient was given ADA at 40 mg biweekly for her active arthritis which had been refractory to 6 mg/week of methotrexate (MTX), and 5 mg/day of prednisolone (PSL). One hundred and six days later, she was admitted to our hospital because of fever, cough, and dyspnea. Another patient is a 62-year-old man who had a history of RA for 3 years. Since his arthritis was so active even under the treatment with MTX (8 mg/week) and PSL (15 mg/day), the patient started to be given ADA at 40 mg biweekly. After 28 days, the patient was admitted to the hospital because of dyspnea. Chest roentgenogram and computed tomography revealed interstitial pneumonia in both patients. Beta-D-glucan levels were so high in their serum suggesting the diagnosis of PCP, which was confirmed by the detection of Pneumocystis jirovecii DNA in the sputa by polymerase chain reaction. The patients were immediately treated with sulfamethoxazole/trimethoprim and high-dose prednisolone, which successfully improved pneumonia, and they were discharged from the hospital on the 8(th) and 16(th) day, respectively. PCR and β-D-glucan were useful for the early diagnosis of PCP and lead to the timely induction of adequate treatment and the rescue of these patients.
22911089 Detection of Legionella pneumophila serogroup 1 in blood cultures from a patient treated w 2013 Feb A 65-year-old man was admitted to our hospital with a temperature of 39.3 °C, cough, sputum, and pharyngeal discomfort that had persisted for 3 days. He had been treated with methotrexate and adalimumab (a tumor necrosis factor-alpha [TNF-α] inhibitor) for rheumatoid arthritis for 2 years, and he had also been treated with S-1 (tegafur, gimeracil, and oteracil potassium) for pancreatic metastasis of gastric cancer for 2 months. Regardless of the underlying pathologies, his general condition was good and he had worked as an electrician until 2 days before admission. However, his appetite had suddenly decreased from the day before admission, and high fever and hypoxia were also evident upon admission. A chest X-ray and computed tomography scan revealed left pleural effusion and consolidation in both lungs. The pneumonia severity index score was 165 and the risk class was V. Accordingly, we started to treat the pneumonia with a combination of levofloxacin and meropenem. Thereafter, we received positive urinary antigen test findings for Legionella pneumophila. After hospitalization, hypoxia was progressed and hypotension was emerged. Despite the application of appropriate antibiotics, vasopressors, and oxygenation, the patient died 8 h after admission. Even after his death, blood cultures were continued to consider the possibility of bacterial co-infection. Although no bacteria were detected from blood cultures, Gimenez staining revealed pink bacteria in blood culture fluids. Subsequent blood fluid culture in selective medium revealed L. pneumophila serogroup 1. Recently, TNF-α inhibitors have been described as a risk factor for Legionnaires' disease. In consideration of the increased frequency of TNF-α inhibitors, we may need to recognize anew that L. pneumophila might be a pathogen of severe community-acquired pneumonia.
21416774 Merkel cell carcinoma in a patient treated with adalimumab: case report. 2011 Feb Merkel cell carcinoma (MCC) is a rare aggressive neuroendocrine tumor that manifests as an asymptomatic enlarging lesion often in the setting of immunosuppression, advanced age, or UV exposure. Immunosuppression has been associated with melanoma, lymphoma, and nonmelanoma skin cancer (NMSC). We present a case of a patient with a long-standing history of rheumatoid arthritis treated with adalimumab, methotrexate, and prednisone who developed a painless, rapidly enlarging lesion that was found to be MCC with lymph node involvement. As the use of tumor necrosis factor (TNF) alpha inhibitors becomes more popular, it is important to identify the potential long-term risks associated with chronic immune modulation. Systemic immunosuppression may be a risk factor for the development of advanced-stage MCC. Treatment with the TNF-alpha inhibitor adalimumab may enhance this risk.
22047935 Modern treatment strategies in rheumatoid arthritis. 2011 Nov The main aim of the thesis was to evaluate the impact of modern treatment strategies on disease activity and disease course in patients with rheumatoid arthritis (RA), and to identify predictors for treatment response. Two different treatment strategies were investigated: (A) Aggressive, conventional treatment aiming at achieving inflammatory control in patients with recent-onset RA and (B) Treatment with tumour necrosis factor alpha (TNFα) inhibitors in patients with RA, who had an incomplete response to conventional treatment. (A) was studied in a randomized, placebo-controlled clinical trial (CIMESTRA), whereas (B) was investigated in an observational, nationwide cohort study (the DANBIO database). The main findings were: 1. Treatment strategy (A) with methotrexate (MTX) and injections of glucocorticoids into swollen joints had rapid and sustained effect and reduced disease activity and halted joint damage. Addition of cyclosporine during the first 2 years reduced disease activity for as long as it was given, but had no effect on the development of joint damage. After 5 years, the majority of the patients was in remission and had no progression of structural joint damage. 2. Bone marrow oedema by Magnetic resonance imaging (MRI) scans of the wrists predicted the development of structural joint damage 2 to 5 years later (based on x-rays). Anti-CCP antibodies and structural joint damage at the start of treatment were also independent predictors for joint damage after 5 years. 3. Routine registration of adverse events observed in patients who received treatment with etanercept or infliximab (TNFα inhibitors) in the DANBIO database picked up twice as many serious adverse events than the spontaneous, mandatory reports to the Danish Medicines Agency. 4. Despite changes in prescription practice for the treatment with TNFα inhibitors in clinical practice from year 2000 to year 2005 towards less stringent treatment criteria, DANBIO data showed an improved treatment response. 5. High age, low functional status and concomitant treatment with prednisolone were negative predictors of a EULAR good response and remission after 6 months of treatment with TNFα inhibitors in clinical practice. 6. In patients, who were naïve to treatment with TNFα inhibitors, significant differences between drugs were observed regarding treatment responses and adherence to therapies. Infliximab had the lowest treatment response, remission rates and adherence to therapy. Adalimumab had the highest treatment response and remission rates, whereas etanercept had the highest adherence. In conclusion, the results from the CIMESTRA trial and the DANBIO database showed that an aggressive treatment strategy with conventional drugs and intra-articular injections with betamethasone effectively controlled disease activity and prevent structural joint damage in patients with early RA. TNFα inhibitors were efficacious in clinical practice in the treatment of RA patients that had failed conventional treatment. Differences between the TNFα inhibitors regarding efficacy and drug adherence were found. Predictors of disease course and treatment response were identified.
22236091 Disability outcomes and dose escalation with etanercept, adalimumab, and infliximab in rhe 2012 Apr INTRODUCTION: Rheumatoid arthritis (RA) is a chronic disease that if left untreated may substantially impair physical functioning. Etanercept, infliximab, and adalimumab are tumor necrosis factor (TNF) blockers whose FDA-approved indications in the US include moderate to severe RA. TNF-blocker dose escalation has been well documented in the literature; however, the comparative effectiveness of these agents remains uncertain. OBJECTIVE: To compare the effectiveness and dose escalation rates of etanercept, adalimumab, and infliximab in US community settings. We hypothesized that etanercept would be equivalent to infliximab and adalimumab in patient-reported disability 9-15 months after therapy initiation, and that fewer etanercept patients would experience dose escalation. METHODS: This is a retrospective analysis of the Arthritis, Rheumatism, and Aging Medical Information System (ARAMIS). Adult patients with no biologic use 6 months before TNF-blocker initiation (index) and with Health Assessment Questionnaire Disability Index (HAQ-DI) scores at index and 9-15 months after index were analyzed (218 etanercept, 93 infliximab, and 40 adalimumab). RESULTS: HAQ-DI change scores at 9-15 months did not differ by treatment (-0.12, -0.10, and -0.08 points for etanercept, infliximab, and adalimumab, respectively; p = 0.52). Dose increases were observed in 1.4% of etanercept, 10.8% of infliximab (p < 0.001), and 12.5% of adalimumab patients (p = 0.004). HAQ-DI change was associated with pre-index HAQ-DI score (p < 0.0001) and disease duration (p = 0.001). CONCLUSIONS: Fewer etanercept patients escalated dose than infliximab or adalimumab patients, but improvements in functional disability were similar. These differences may have been influenced by package labeling, mode of administration, or other factors. RA treatment with infliximab and adalimumab in community settings, characterized by dose escalation, did not yield greater disability improvements compared to etanercept, which remained at a relatively stable dose. Uncontrolled treatment selection in this observational design may have influenced outcomes, and prior methotrexate treatment may partly explain disability improvements smaller than typically observed in clinical trials.
21834061 Antibody response is reduced following vaccination with 7-valent conjugate pneumococcal va 2011 Dec OBJECTIVE: To study the influence of antiinflammatory treatments, including methotrexate (MTX) and tumor necrosis factor (TNF) inhibitors, on antibody response following vaccination using a 7-valent conjugate pneumococcal vaccine in adult patients with established arthritis. METHODS: Patients with rheumatoid arthritis (RA) or spondylarthropathy (SpA) (including psoriatic arthritis) were vaccinated (n = 505). All patients were stratified into 6 prespecified groups based on diagnosis and treatment (RA patients receiving MTX, RA patients receiving anti-TNF agents and MTX, RA patients receiving TNF inhibitors as monotherapy, SpA patients receiving anti-TNF agents and MTX, SpA patients receiving TNF inhibitors as monotherapy, and SpA patients receiving nonsteroidal antiinflammatory drugs [NSAIDs] and/or analgesics). SpA patients receiving only NSAIDs/analgesics served as a control group. All patients received 1 dose (0.5 ml) of vaccine intramuscularly. Levels of IgG antibodies against 23F and 6B serotypes were measured at vaccination and at 4-6 weeks following vaccination, using standardized enzyme-linked immunosorbent assays. RESULTS: Positive antibody response was defined as an antibody response ratio (ARR) (i.e., ratio of post- to prevaccination antibody levels) of ≥2. The ARR differed significantly between the groups. A better ARR was seen among patients in the control group compared to those in groups treated with MTX or MTX in combination with TNF inhibitors. Among patients treated with TNF inhibitors as monotherapy, ARRs for both serotypes were lower numerically, but were not significantly different, compared to those in controls. Ongoing MTX treatment was predictive of reduced response (odds ratio 0.41 [95% confidence interval 0.24-0.68], P = 0.001). Higher age was associated with impaired positive antibody response. Concomitant prednisolone treatment elicited better positive antibody response in patients with RA. CONCLUSION: Treatment with MTX and higher age were predictive of an impaired antibody response to the 7-valent conjugate pneumococcal vaccine in this cohort of patients with chronic arthritis. TNF inhibitors did not significantly affect antibody responses.
22121511 Changes in cotherapies after initiation of disease-modifying antirheumatic drug therapy in 2011 Oct Objective. We hypothesized that initiation of a new disease-modifying antirheumatic drug (DMARD) for treatment of rheumatoid arthritis (RA) would decrease the use of corticosteroids, nonsteroidal antiinflammatory drugs (NSAIDs), and narcotics.Methods. Using administrative databases, we assembled 4 retrospective cohorts of RA patients (1998-2005) and identified 5 groups initiating DMARD regimens: methotrexate (MTX) with (new MTX) or without (first MTX) use of other nonbiologic DMARDs in the previous year; new hydroxychloroquine (HCQ) and/or sulfasalazine (SSZ; new HCQ/SSZ)and new leflunomide (new LEF), both with previous use of MTX; and new tumor necrosis factor α (TNFα) antagonists(new anti-TNF). We compared within-person differences in any use of cotherapies (≥ prescription) between the 6 months before and the 6-12 months after DMARD initiation.Results. Among 32,476 DMARD initiators, the prevalence of corticosteroid, NSAID, and narcotic use increased by 15%, 5%,and 6%, respectively, in the 6 months before initiation compared to the previous 6 months, suggesting worsening of the disease. In the 6-12 months after initiation for most initiator groups, more patients stopped using corticosteroids and NSAIDs than started, with overall decreases of 8.9% (95% confidence interval [95% CI] 8.4-9.4%) for corticosteroids and 12.9% (95%CI 12.3-13.4%) for NSAIDs. The proportion of narcotic users changed little (overall decrease of 2.5%; 95% CI 1.9-3.0%).Conclusion. Use of all 3 cotherapies increased in the 6 months before initiation of new DMARD regimens for RA. Use of corticosteroids and NSAIDs decreased modestly 6-12 months after initiation, but there was only a very small decrease in narcotic use. These differential changes require further study.
23179002 Clinical outcome in patients with rheumatoid arthritis switched to tocilizumab after etane 2013 Feb The present study retrospectively assessed the efficacy of tocilizumab in patients with rheumatoid arthritis (RA) who failed to respond to treatment with etanercept or infliximab. A retrospective study of 33 RA patients who did not respond to etanercept or infliximab was conducted. Responses of subjects switching from etanercept to tocilizumab (n = 17) were compared with those switching from infliximab to tocilizumab (n = 16). Treatment with disease-modifying antirheumatic drugs before the switch, especially methotrexate (MTX), was maintained. Disease activity was assessed by the Disease Activity Score 28-C Reactive Protein (DAS28-CRP), the Simplified Disease Activity Index (SDAI), and the Clinical Disease Activity Index (CDAI). Patients who switched from etanercept were significantly less likely to have used MTX and were significantly older than patients who switched from infliximab. In both groups, there was a significant reduction from baseline in DAS28-CRP, SDAI, and CDAI values at 24 weeks with no significant differences between groups. However, at week 52, DAS28-CRP, SDAI, and CDAI values in the group switched from etanercept were significantly worse than those in the group switched from infliximab. All patients switched from infliximab were using MTX. In the evaluation between patients who switched from etanercept monotherapy, etanercept plus MTX, and infliximab plus MTX, a significant improvement from baseline was seen in DAS28-CRP, SDAI, and CDAI for all patients at 24 weeks with no significant differences between groups. Disease activity was maintained at 52 weeks in the group that switched from etanercept plus MTX and infliximab plus MTX. However, the efficacy of tocilizumab was decreased in the group that switched from etanercept monotherapy. Switching from etanercept plus MTX or from infliximab plus MTX to tocilizumab plus MTX improved response to therapy, but switching from etanercept monotherapy to tocilizumab monotherapy did not improve response to therapy.
22020266 Cervical human papillomavirus infection in Mexican women with systemic lupus erythematosus 2012 Apr Cervical human papillomavirus (HPV+) infection is associated with an increased risk of cervical dysplasia. Although the frequency of HPV+ in systemic lupus erythematosus (SLE) has been investigated in some races its prevalence in Hispanic women is still unknown. This cross-sectional study evaluated the prevalence of cervical HPV+ in Mexican women with SLE (n = 34) or rheumatoid arthritis (RA) (n = 43) and in healthy controls (n = 146). These women were interviewed about risk factors for sexually transmitted infections and cervical cytology analysis was performed. HPV+ viral types were identified using PCR: HPV+ was observed in 14.7% of SLE, 27.9% of RA and 30.8% of controls. High-risk HPV types were observed in 11.7% of women with SLE, 27.9% of women with RA, and in 26% of the controls. High-risk viral types 58, 35 and 18 were the most frequently identified in SLE. Two women with SLE had a high-grade squamous intraepithelial lesion and one had cervical cancer. An association was observed between methotrexate utilization, longer duration of therapy with prednisone, and HPV+ in RA or SLE. Thus, there is a high prevalence of cervical HPV infection in Mexican women with SLE or RA, and physicians must be vigilant in preventing the development of cervical dysplasia.
21360491 Evaluation of the safety of rituximab in combination with a tumor necrosis factor inhibito 2011 Mar OBJECTIVE: To assess the safety of rituximab in combination with a tumor necrosis factor (TNF) inhibitor and methotrexate (MTX) in patients with rheumatoid arthritis (RA). METHODS: Adult patients with active RA (≥ 5 swollen and ≥ 5 tender joints) receiving a stable dose of MTX (10-25 mg/week) and stable dose of TNF inhibitor (etanercept or adalimumab) for ≥ 12 weeks were randomized 2:1 to receive one course of rituximab or placebo, given intravenously at a dose of 2 × 500 mg. The primary end point was the proportion of patients developing ≥ 1 serious infection through week 24. RESULTS: Fifty-one patients were treated with either rituximab or placebo in combination with background MTX and a TNF inhibitor. Baseline characteristics were generally balanced between groups, except for corticosteroid usage (36% in the rituximab arm versus 17% in the placebo arm). A serious infection (pneumonia) was observed in 1 patient (3%) in the rituximab group after 14.4 patient-years of exposure (6.95 events per 100 patient-years, 95% confidence interval 0.98-49.35), compared with none in the placebo group at week 24. Infections were reported in 18 patients (55%) and 11 patients (61%) in the rituximab and placebo groups, respectively. Grade 3 infections were reported in 3 patients (9%) receiving rituximab and in none of the patients receiving placebo. No grade 4 infections were observed, nor were there any opportunistic, fungal, or tuberculosis infections. Serious adverse events (SAEs) were reported in 2 rituximab-treated patients (pneumonia and coronary artery occlusion), whereas there were no SAEs reported in placebo-treated patients. At week 24, the percentage of patients achieving an American College of Rheumatology 20% (ACR20) improvement response was 30% in the rituximab group compared with 17% in the placebo group, and ACR50 responses were achieved by 12% and 6% of patients, respectively. CONCLUSION: The preliminary safety profile of rituximab in combination with a TNF inhibitor and MTX was consistent with the safety profile of rituximab in combination with MTX in other RA trials without a TNF inhibitor, with no new safety signals observed. SAEs were numerically more frequent in the rituximab group, and there was no clear evidence of an efficacy advantage in patients receiving rituximab in combination with a TNF inhibitor and MTX.
21240503 Treatment of refractory adult-onset Still's disease with tocilizumab: report of two cases 2011 Dec Adult-onset Still's disease (AOSD) is empirically treated with nonsteroidal anti-inflammatory drugs, corticosteroids, conventional disease-modifying antirheumatic drugs, tumor necrosis factor-blocking agents or anakinra. The monoclonal anti-interleukin (IL)-6 antibody tocilicumab (TOC) has recently been approved for the treatment of rheumatoid arthritis and may be an attractive therapeutic option for AOSD as well. We report two AOSD patients treated with TOC and review of the current data on the use of TOC in AOSD. TOC was applied to the first patient after failure of cloroquin, methotrexate, adalimumab and etanercept. The second patient received TOC because of inefficacious methotrexate treatment. TOC was well tolerated by both the patients, and no clinically significant side effects occurred. Including these two cases, a total of seven AOSD patients have been successfully treated with TOC so far. TOC may be a promising treatment option for AOSD patients refractory to conventional disease-modifying antirheumatic drugs anakinra and tumor necrosis factor-[Formula: see text].
23010097 Adult-onset Still's disease: clinical, serological and therapeutic considerations. 2013 Jan OBJECTIVES: This paper aims to describe the clinical manifestations, laboratory abnormalities and treatment of adult-onset Still's disease (AOSD) in Greek patients. METHODS: This is a retrospective observational study. Forty-four patients, diagnosed with AOSD, followed since 1985 up to June 2011, were included. The disease course and treatment were recorded and compared to previously published studies. RESULTS: Twenty-one males and 23 females were identified. Mean age at diagnosis was 38.3 years. The most common clinical manifestations were fever (100%), arthralgias (97.7%), arthritis (93.2%), salmon-coloured rash (84%), myalgias (50%) and sore throat (38.6%). Characteristic laboratory abnormalities were leucocytosis with neutrophilia (81.8%), elevated C-reactive protein (100%) and erythrocyte sedimentation rate (100%). Elevated liver enzymes and hyperferritinaemia were found in 50% and in 59% of the patients respectively. Very high ferritin serum levels (>5000 μg/l) were found in 22.7%. Rheumatoid factor and antinuclear antibodies were negative in all patients. Thirty patients (68.2%) received non-steroidal anti-inflammatory drugs or aspirin with or without corticosteroids. Response to corticosteroids was common (58.9%). When this treatment was ineffective, a disease-modifying anti-rheumatic drug (DMARD), usually methotrexate, was added with a response rate of 63.6%. Anakinra was used in cases resistant to conventional immunosuppressive treatment. Ten out of 44 patients (22.7%) were treated with anakinra and response was achieved in all of them. CONCLUSIONS: Our results regarding clinical manifestations and laboratory abnormalities were similar to those of previous reports. High ferritin serum levels were reported in all studies of AOSD and are considered as diagnostically valuable. When treatment with corticosteroids and DMARDS had failed, biologic agents such as anakinra were successfully applied.