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ID PMID Title PublicationDate abstract
28516872 Glucocorticoid-sparing effect of first-year anti-TNFα treatment in rheumatoid arthritis ( 2017 Jul OBJECTIVES: Anti-TNFα agents are indicated in selected patients with rheumatoid arthritis (RA) who respond inadequately to methotrexate and particularly when glucocorticoids are mandatory. We evaluated whether a glucocorticoid-sparing effect occurred during the first year of anti-TNF-α therapy. METHODS: Between 2007 and 2009, the French multicentre, longitudinal, prospective, observational, population-based CORPUS cohort included biologic-naive patients with inflammatory joint disease. Patients with active RA treated with glucocorticoids were included. Patients who received at least one anti-TNFα injection during follow-up were compared to anti-TNF-α non-users. RESULTS: Among the 205 patients, 76.1% were women, mean disease duration was 7.7±8.3 years, mean DAS28 was 5.2±1.3, mean follow-up was 13.1±2.8 months, and mean prednisone dose was 9.9±9.6 mg/day. The 75 (36.6%) anti-TNF-α recipients were younger, had a longer RA duration, more often tested positive for rheumatoid factor and anti-citrullinated peptide antibody, more often received previous DMARDs, received a higher methotrexate dosage, had fewer intra-articular glucocorticoid injections at baseline and were more often followed by hospital practitioners than non-recipients. Mean prednisone dosage decreased from 11.8±12.7 to 5.9±9.7 mg/day in recipients and from 8.7±7.1 to 5.0±4.4 mg/day in non-recipients. Prednisone was stopped more often among recipients (21/59, 35.6%) than among non-recipients (16/94, 17.0%) (p=0.01). By multivariate analysis, factors independently associated with lower prednisone requirements were baseline daily prednisone dosage, a CRP >10 mg/l and not to be followed by an office-based practitioner. CONCLUSIONS: This study showed a significantly higher glucocorticoid discontinuation rate among anti-TNF-α recipients than among non-recipients. However, the glucocorticoid-sparing effect was small and not observed by multivariate analysis.
29041951 A new bioassay for measuring the strength of IL-6/STAT3 signal inhibition by tocilizumab i 2017 Oct 17 BACKGROUND: Interleukin-6 (IL-6) transduces signals via phosphorylation of STAT3 (pSTAT3). Tocilizumab (TCZ) is an IL-6 receptor blocker, which, when administered intravenously every 4 weeks, efficiently ameliorates rheumatoid arthritis (RA). Since IL-6 signal strength varies among patients with RA, the intensity necessary for appropriate IL-6 signal inhibition by TCZ might vary between individuals. In a previous study, we have examined the clinical utility of increasing (dosing interval shortened to 3 weeks) and decreasing (interval extended to 5 weeks) the dose frequency of TCZ. However, there is currently no established method for accurately measuring the strength of IL-6 signal inhibition by TCZ among individual patients. We therefore sought to develop such an assay. METHODS: Whole blood samples were collected from RA patients with low disease activity (clinical disease activity index (CDAI) ≤ 10) who were treated with TCZ at dosing intervals of 3 weeks (3-week group, n = 10), 4 weeks (4-week group, n = 10) or 5 weeks (5-week group, n = 10), or with methotrexate (control group, n = 10). Recombinant human IL-6 (0, 0.1, 1, 10, 100 ng/ml) was exogenously added to whole blood and the proportion of pSTAT3-positive CD4+ T cells (%pSTAT3+/CD4+) was measured by Phosflow cytometric analysis. RESULTS: The addition of exogenous IL-6 increased the proportion of pSTAT3-positive CD4+ T cells in a dose-dependent manner in each group. Inhibition of IL-6 signaling was strongest in the 3-week dosing group, followed by the 4-week, 5-week and control group. Significant differences in %pSTAT3+/CD4+ cells were observed between dose interval groups when stimulated with 10 ng/ml and 100 ng/ml of IL-6. CONCLUSION: Assessment of the proportion of pSTAT3-positive CD4+ T cells under IL-6 stimulation is a highly sensitive and useful method for determining differences in the strength of IL-6 signal inhibition in patients treated with TCZ. It is suggested that different TCZ treatment intervals were necessary to lower disease activity in each group of patients, and these findings also indicate that the IL-6 signaling pathway may differ in each RA patient. Our assay may support strategies for optimizing TCZ treatment in RA patients.
28356243 Efficacy of glucocorticoids, conventional and targeted synthetic disease-modifying antirhe 2017 Jun OBJECTIVES: To perform a systematic literature review (SLR) informing the 2016 update of the recommendations for the management of rheumatoid arthritis (RA). METHODS: An SLR for the period between 2013 and 2016 was undertaken to assess the efficacy of glucocorticoids (GCs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and targeted synthetic DMARDs (tsDMARDs) (tofacitinib and baricitinib) in randomised clinical trials. RESULTS: For GCs, four studies were included in the SLR. Patients without poor prognostic factors experienced benefit when GCs were added to methotrexate (MTX). Lower doses of GCs were similar to higher doses. For csDMARDs, two new studies comparing MTX monotherapy with combination csDMARD were included in the SLR. In the tREACH trial at the end of 12 months no difference between the groups in disease activity, functional ability and radiographic progression was seen, using principles of tight control (treat-to-target). In the CareRA trial, combination therapy with csDMARDs was not superior to MTX monotherapy and monotherapy was better tolerated.For tsDMARDs, tofacitinib and baricitinib were shown to be more effective than placebo (MTX) in different patient populations. CONCLUSIONS: Addition of GCs to csDMARD therapy may be beneficial but the benefits should be balanced against the risk of toxicity. Under tight control conditions MTX monotherapy is not less effective than combination csDMARDs, but better tolerated. Tofacitinib and baricitinib are efficacious in patients with RA, including those with refractory disease.
27993828 Filgotinib (GLPG0634/GS-6034), an oral selective JAK1 inhibitor, is effective as monothera 2017 Jun OBJECTIVES: To evaluate the efficacy and safety of different doses of filgotinib, an oral Janus kinase 1 inhibitor, as monotherapy in patients with active rheumatoid arthritis (RA) and previous inadequate response to methotrexate (MTX). METHODS: In this 24-week phase IIb study, patients with moderately to severely active RA were randomised (1:1:1:1) to receive 50, 100 or 200 mg filgotinib once daily, or placebo, after a ≥4-week washout from MTX. The primary end point was the percentage of patients achieving an American College of Rheumatology (ACR)20 response at week 12. RESULTS: Overall, 283 patients were randomised and treated. At week 12, significantly more patients receiving filgotinib at any dose achieved ACR20 responses versus placebo (≥65% vs 29%, p<0.001). For other key end points at week 12 (ACR50, ACR70, ACR-N, Disease Activity Score based on 28 joints and C reactive protein, Clinical Disease Activity Index, Simplified Disease Activity Index and Health Assessment Questionnaire-Disability Index) significant differences from baseline in favour of filgotinib 100 and 200 mg versus placebo were seen; responses were maintained or improved through week 24. Rapid onset of action was observed for most efficacy end points. Dose-dependent increases in haemoglobin were observed. The percentage of patients with treatment-emergent adverse events (TEAE) was similar in the placebo and filgotinib groups (∼40%). Eight patients on filgotinib and one on placebo had a serious TEAE, and four patients, all of whom received filgotinib, experienced a serious infection. No tuberculosis or opportunistic infections were reported. CONCLUSIONS: Over 24 weeks, filgotinib as monotherapy was efficacious in treating the signs and symptoms of active RA, with a rapid onset of action. Filgotinib was generally well tolerated. TRIAL REGISTRATION NUMBER: NCT01894516.
27181115 The efficacy and safety of additional administration of tacrolimus in patients with rheuma 2017 Jan OBJECTIVES: Tocilizumab (TCZ) shows good retention in patients with rheumatoid arthritis (RA), but no previous reports demonstrated hopeful treatment options against inadequate response to TCZ. Tacrolimus (TAC) has proved to show efficacy against inadequate response to tumor necrosis factor alpha inhibitors, yet its add-on effects on TCZ remain unknown. METHODS: Twenty patients with RA (17 women, age 58.6 years, disease duration 12.1 years, prior TCZ duration 2.6 years, 18 intravenous [8 mg/kg/month] and 2 subcutaneous [324 mg/month] TCZ treatments, methotrexate 6.1 mg/week [70.0%]) who showed an inadequate response to TCZ (clinical disease activity index [CDAI] ≥ 5.8, 18 secondary non-responders) were additionally treated with TAC (1.1 mg/day), and enrolled in this 24-week, prospective study. RESULTS: Seventeen patients (85.0%) continued the treatment for 24 weeks. Statistically significant decreases in outcome measures were as follows: disease activity score based on 28 joints with C-reactive protein (DAS28-CRP) from 3.3 at baseline to 2.1 at week 24 (p < 0.001), CDAI from 17.7 to 7.6 (p < 0.001), and serum matrix metalloproteinase-3 levels from 232.8 to 66.2 ng/ml (p < 0.001). About 15 patients (75%) achieved low disease activity or remission (DAS28-CRP ≤2.7 or CDAI ≤10) at week 24. CONCLUSIONS: Adding low-dose TAC to inadequate responders to TCZ may be a promising complementary treatment option.
28120731 [Serious complications during treatment with methotrexate: also in chronic low-dosage use] 2017 Methotrexate is a frequently prescribed drug and is considered to be safe at a low dosage. However, serious complications may occur during treatment. In this article we describe a 78-year-old male who used low-dose methotrexate for psoriatic arthritis. He died of multi-organ failure caused by sepsis and methotrexate intoxication as a result of deteriorating renal function. The second patient was a 56-year-old male who used low-dose methotrexate for rheumatoid arthritis. This patient developed pancytopenia and methotrexate pneumonitis during treatment with methotrexate. We recommend the frequent monitoring of blood count and renal and liver function tests to detect early deterioration. Furthermore, doctors should be aware of conditions and factors predisposing to methotrexate intoxication, such as impaired kidney function and co-medication. If methotrexate intoxication is suspected, intravenous folinic acid should be administered immediately.
29213000 [A methotrexate-associated lympholiferative disorder patient with gastrointestinal perfora 2017 A 70-year-old woman was diagnosed with chronic rheumatoid arthritis and treated with methotrexate and prednisolone. She visited our hospital to determine the cause of her continuous fatigue and fever for the past three weeks. She consumed no food orally and was provided antibiotics because free air was found on computed tomography (CT). Intraperitoneal small lymphadenopathy and swelling of both adrenal glands was also found on CT, and MTX-associated lymphoproliferative disorder (MTX-LPD) was suspected. Am adrenal gland biopsy showed diffuse large B-cell lymphoma (DLBCL) associated with MTX-LPD. The causes of gastrointestinal perforation with collagen diseases have been reported to be functional gastrointestinal disorders with collagen diseases like amyloidosis, gastrointestinal infections in immunocompromised patients, and side effects of medication, such as steroids or NSAIDs and MTX. MTX-LPD is an uncommon side effect of methotrexate. To ensure its appropriate diagnosis and treatment, it is important to improve the degree of recognition of MTX-LPD, and a prompt response is needed.
28748514 A systemic review and meta-analysis of the clinical efficacy and safety of total glucoside 2018 Jan To assess the efficacy and safety of the combination of total glucoside of peony (TGP) and methotrexate (MTX) for the treatment of rheumatoid arthritis (RA). Randomized controlled trial (RCT) data on the traditional Chinese active component TGP combined with MTX vs. MTX alone for the treatment of RA was collected by searching the Pubmed, Embase, Cochrane Library, CNKI, VIP Journals database, and Wanfang database up to February 2017. Study selection, data extraction, data synthesis, and data analyses were performed according to the Cochrane standards. A total of eight RCTs involving 522 participants were included in this meta-analysis. Compared with MTX alone, the use of TGP combined with MTX exhibited better therapeutic effects for the treatment of RA (P = 0.004). In addition, TGP combined with MTX caused a more significant decrease in erythrocyte sedimentation rate (ESR) (P < 0.0001) and swollen joint count (SJC) (P < 0.00001). However, no significant differences were found in C-reactive protein (CRP) (P = 0.19), duration of morning stiffness (DMS) (P = 0.32), or tender joint count (TJC) (P = 0.23) between the two groups. In addition, adverse events were more frequently reported in the MTX monotherapy group than in the TGP and MTX combination group (P = 0.0007). Our study demonstrates that TGP combined with MTX is more effective than MTX alone for the treatment of RA. Nevertheless, the adverse effects of the combination of TGP and MTX need to be further assessed. Due to the poor methodological quality of included trials, well-designed, multi-center, and large-scale RCTs are necessary to draw a more definitive conclusion.
28865493 High titers of both rheumatoid factor and anti-CCP antibodies at baseline in patients with 2017 Sep 2 BACKGROUND: Although both rheumatoid factor (RF) and anticyclic citrullinated peptide antibodies (anti-CCP) are useful for diagnosing rheumatoid arthritis (RA), the impact of these autoantibodies on the efficacy of tumor necrosis factor (TNF) inhibitors has been controversial. The aim of this post hoc analysis of a randomized double-blind study (the RISING study) was to investigate the influences of RF and anti-CCP on the clinical response to infliximab in patients with RA. METHODS: Methotrexate-refractory patients with RA received 3 mg/kg of infliximab from weeks 0 to 6 and then 3, 6, or 10 mg/kg every 8 weeks from weeks 14 to 46. In this post hoc analysis, patients were stratified into three classes on the basis of baseline RF/anti-CCP titers: "low/low-C" (RF < 55 IU/ml, anti-CCP < 42 U/ml), "high/high-C" (RF ≥ 160 IU/ml, anti-CCP ≥ 100 U/ml), and "middle-C" (neither low/low-C nor high/high-C). Baseline plasma TNF level, serum infliximab level, and disease activity were compared between the three classes. RESULTS: Baseline RF and anti-CCP titers showed significant correlations with baseline TNF and infliximab levels in weeks 2-14. Comparison of the three classes showed that baseline TNF level was lowest in the low/low-C group and highest in the high/high-C group (median 0.73 versus 1.15 pg/ml), that infliximab levels at week 14 were highest in the low/low-C group and lowest in the high/high-C group (median 1.0 versus 0.1 μg/ml), and that Disease Activity Score in 28 joints based on C-reactive protein at week 14 was lowest in the low/low-C group and highest in the high/high-C group (median 3.17 versus 3.82). A similar correlation was observed at week 54 in the 3 mg/kg dosing group, but not in the 6 or 10 mg/kg group. Significant decreases in both RF and anti-CCP were observed during infliximab treatment. CONCLUSIONS: RF/anti-CCP titers correlated with TNF level. This might explain the association of RF/anti-CCP with infliximab level and clinical response in patients with RA. Baseline RF/anti-CCP titers may serve as indices that aid infliximab treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00691028 . Retrospectively registered on 3 June 2008.
27846189 The plausible association of MTHFR and ADORA2A polymorphisms with nodules in rheumatoid ar 2017 Feb OBJECTIVE: The treatment of rheumatoid arthritis (RA) patients with methotrexate (MTX) is linked to the development or progression of rheumatoid nodules. The aim of this study was to determine whether folate and adenosine pathways-related single nucleotide polymorphisms might be predictive of increased nodule formation in RA patients treated with oral MTX. METHODS: A total of 185 Caucasian RA patients were enrolled in this cross-sectional study, all of whom fulfilled the 1987 RA criteria of the American College of Rheumatology; each patient had a history of MTX treatment. RESULTS: A higher frequency of the MTHFR 1298AA genotype was found in 17 (70.8%) of 24 patients with general nodules [odds ratio (OR)=3.08, 95% confidence interval (CI): 1.20-7.69] and in 14 (73.7%) of 19 patients who developed nodules during MTX treatment (OR=3.55, 95% CI: 1.22-10.32). In contrast, a negative association with nodules during MTX treatment (OR=0.29, 95% CI: 0.08-1.10) was found for 19 (79.2%) patients with the TT genotype (rs2298383) in the adenosine A2a receptor gene (ADORA2A). However, the significance did not remain upon correction for multiple testing. The combination of MTHFR 1298AA along with ADORA2A rs2298383 CC or CT genotypes occurring in one-third of RA patients showed a higher frequency of general nodules 15/59 (25.4%) as well as developing nodules during MTX treatment 13/59 (22.0%) in comparison with the overall studied group: 24/185 (13.0%) and 19/185 (10.3%), respectively. CONCLUSION: This exploratory study indicates for the first time a plausible association of adenosine and folate pathways single nucleotide polymorphisms in nodules' etiopathogenesis.
27993829 Filgotinib (GLPG0634/GS-6034), an oral JAK1 selective inhibitor, is effective in combinati 2017 Jun OBJECTIVES: To evaluate the efficacy and safety of different doses and regimens of filgotinib, an oral Janus kinase 1 inhibitor, as add-on treatment to methotrexate (MTX) in patients with active rheumatoid arthritis (RA) and inadequate response to MTX. METHODS: In this 24-week phase IIb study, patients with moderate-to-severe active RA receiving a stable dose of MTX were randomised (1:1:1:1:1:1:1) to receive placebo or 50, 100 or 200 mg filgotinib, administered once daily or twice daily. Primary end point was the percentage of patients achieving a week 12 American College of Rheumatology (ACR)20 response. RESULTS: Overall, 594 patients were randomised and treated. At week 12, significantly more patients receiving filgotinib 100 mg once daily or 200 mg daily (both regimens) achieved an ACR20 response versus placebo. For other key end points at week 12 (ACR50, ACR-N, Disease Activity Score based on 28 joints and C reactive protein value, Clinical Disease Activity Index, Simplified Disease Activity Index and Health Assessment Questionnaire-Disability Index), differences in favour of 100  or 200 mg filgotinib daily were seen versus placebo; responses were maintained or improved through to week 24. Rapid onset of action and dose-dependent responses were observed for most efficacy end points and were associated with an increased haemoglobin concentration. No significant differences between once-daily and twice-daily regimens were seen. Treatment-emergent adverse event rates were similar in placebo and filgotinib groups. Serious infections occurred in one and five patients in the placebo and filgotinib groups, respectively. No tuberculosis or opportunistic infections were reported. CONCLUSIONS: Filgotinib as add-on to MTX improved the signs and symptoms of active RA over 24 weeks and was associated with a rapid onset of action. Filgotinib was generally well tolerated. TRIAL REGISTRATION NUMBER: NCT01888874.
28794381 Clinical Characteristics of Rheumatoid Arthritis Patients Achieving Functional Remission a 2017 Sep 1 Objectives We aimed to identify the factors that predict the likelihood of remission based on a health assessment questionnaire (HAQ) in rheumatoid arthritis (RA) patients who received non-tumor necrosis factor (TNF) biologics for six months before they commenced definitive treatment. Methods The subjects consisted of 97 RA patients treated with tocilizumab or abatacept for 6 months. The following characteristics were investigated: age, gender, body mass index, steroid and methotrexate dosage, serum matrix metalloproteinase-3 levels, simplified disease activity index (SDAI) score, HAQ score (for assessing the activities of daily living [ADL]) and the short form (SF)-36 score (for assessing the quality of life [QOL]). Remission based on the HAQ score is defined as HAQ ≤0.5 after 6 months of treatment. The subjects were divided into two groups: patients with HAQ score ≤0.5 and HAQ score >0.5, and a retrospective study was conducted. Results The group of RA patients who entered remission based on the HAQ (53 patients) had a lower SDAI than the patients who did not enter remission (44 patients), and the RA patients had a lower tender joint count (TJC) and HAQ scores and a lower physician's global assessment (PGA) than those who did not enter remission. The physical component summary score (PCS) and role/social component summary score (RCS) of the SF-36 summary score were higher in the remission patients than in those without. Before the start of the treatment, the HAQ score, patients' global assessment (PtGA) and PCS and mental component summary score (MCS) of the SF-36 were determined based on a logistic regression analysis. Conclusion Our findings suggest that RA patients with lower HAQ scores and PtGA and higher PCS and MCS of the SF-36 at baseline are more likely to achieve HAQ remission with non-TNF biologic treatment than others.
28821984 Nonassociation of homocysteine gene polymorphisms with treatment outcome in South Indian T 2018 Feb The aim of the study was to look for any association of MTR 2756A>G and MTRR 66A>G gene polymorphisms with clinical phenotype, methotrexate (MTX) treatment response, and MTX-induced adverse events in South Indian Tamil patients with rheumatoid arthritis (RA). A total of 335 patients with RA were investigated. MTR 2756A>G gene polymorphism was analyzed by PCR-RFLP, and MTRR 66A>G SNP was analyzed by TaqMan 5' nuclease assay. The allele frequencies were compared with HapMap groups. MTR 2756G allele was found to be associated with risk of developing RA. The allele frequencies of MTR 2756A>G and MTRR 66A>G SNPs in controls differed significantly when compared with HapMap groups. Neither of the SNPs influenced the MTX treatment outcome and adverse effects. Neither of the SNPs seems to be associated with MTX treatment outcome and adverse events in South Indian Tamil patients with RA.
27871200 Denosumab: targeting the RANKL pathway to treat rheumatoid arthritis. 2017 Jan Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by focal pathologic bone resorption due to excessive activity of osteoclasts (OC). Receptor activator of nuclear factor kappa B ligand (RANKL) is essential for the proliferation, differentiation, and survival of OC. Denosumab (DMab) is a humanized monoclonal antibody that binds to RANKL with high affinity and blocks its subsequent association with its receptor RANK on the surface of OC precursors. Area covered: The authors review the molecular and cellular mechanisms underlying therapeutic applications of DMab, provide recent highlights on pharmacology, efficacy and safety of DMab, and discuss the potential of DMab as a novel therapeutic option for the treatment of rheumatoid arthritis. Expert opinion: Clinical results suggest that DMab is efficient both in systemic and articular bone loss in RA with limited side effects. Diminished bone erosion activity was also noted in RA patients on corticosteroids and bisphosphonates. Combination of DMab with an anti-TNF agent was not associated with increased infection rates. Collectively, these data indicate that DMab, in combination with methotrexate and possibly other conventional synthetic Disease Modifying Anti-Rheumatic Drugs (csDMARDs), is an effective, safe and cost-effective option for the treatment of RA.
28866645 Optimal methotrexate dose is associated with better clinical outcomes than non-optimal dos 2017 Dec BACKGROUND: Although methotrexate (MTX) is the consensual first-line disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis (RA), substantial heterogeneity remains with its prescription and dosage, which are often not optimal. OBJECTIVE: To evaluate the symptomatic and structural impact of optimal MTX dose in patients with early RA in daily clinical practice over 2 years. METHODS: Patients included in the early arthritis ESPOIR cohort who fulfilled the ACR-EULAR (American College of Rheumatology/European League against Rheumatism) criteria for RA and received MTX as a first DMARD were assessed. Optimal MTX dose was defined as ≥10 mg/week during the first 3 months, with escalation to ≥20 mg/week or 0.3 mg/kg/week at 6 months without Disease Activity Score in 28 joints remission. Symptomatic and structural efficacy with and without optimal MTX dose was assessed by generalised logistic regression with adjustment for appropriate variables. RESULTS: Within the first year of follow-up, 314 patients (53%) with RA received MTX as a first DMARD (mean dose 12.2±3.8 mg/week). Only 26.4% (n=76) had optimal MTX dose. After adjustment, optimal versus non-optimal MTX dose was more efficient in achieving ACR-EULAR remission at 1 year (OR 4.28 (95% CI 1.86 to 9.86)) and normal functioning (Health Assessment Questionnaire ≤0.5; OR at 1 year 4.36 (95% CI 2.03 to 9.39)), with no effect on radiological progression. Results were similar during the second year. CONCLUSION: Optimal MTX dose is more efficacious than non-optimal dose for remission and function in early arthritis in daily practice, with no impact on radiological progression over 2 years.
28288682 Low disease activity for up to 3 years after adalimumab discontinuation in patients with 2017 Mar 14 BACKGROUND: This study was conducted to evaluate the feasibility of long-term adalimumab (ADA) discontinuation after achievement of low disease activity (LDA) in Japanese patients with early rheumatoid arthritis (RA) and to identify predictors of LDA maintenance. METHODS: In the HOPEFUL-1 study, patients received initial therapy with either ADA plus methotrexate (MTX; intensive therapy) or MTX alone (standard therapy) for 26 weeks, followed by ADA + MTX for 26 weeks. In the HOPEFUL-2 study, patients received ADA + MTX (ADA continuation) or MTX alone (ADA discontinuation) for 52 weeks. HOPEFUL-3 was an observational study that enrolled patients who had completed HOPEFUL-2; these patients were followed for an additional 104 weeks. RESULTS: Of the 172 patients enrolled in the HOPEFUL-3 study, 135 (ADA continuation, n = 61; ADA discontinuation, n = 74) with 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP) values at both week 52 (start of HOPEFUL-2) and week 208 (end of HOPEFUL-3) were included in the effectiveness analysis. At week 208, 58 (95.1%) of 61 patients and 59 (79.7%) of 74 patients who continued or discontinued ADA, respectively, had LDA (DAS28-CRP <3.2). Initial intensive therapy was associated with a better outcome than standard therapy in terms of change in modified total Sharp score from week 0 to week 208, which was ≤0.5 (64% vs. 30%). The incidence of adverse events was significantly lower in the ADA discontinuation group than in the ADA continuation group (9.7% vs. 32.9%; p < 0.001). CONCLUSIONS: Approximately 80% of patients who discontinued ADA for 3 years after achieving LDA with ADA + MTX were still in LDA, with a lower incidence of adverse events than patients who continued ADA. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01346501. Registered 29 April 2011.
29043892 Tofacitinib in the treatment of active rheumatoid arthritis in adults. 2018 Jan Tofacitinib, a pan Janus kinase inhibitor, has been investigated as monotherapy in patients naive to methotrexate and in methotrexate incomplete responders and in combination with disease-modifying antirheumatic drugs in antirheumatic drug incomplete responders and TNF inhibitor failures in the Phase II and III programs. The clinical trial program demonstrated efficacy and a reasonable safety profile in these disease populations that has led to the approval of tofacitinib 5 mg twice daily orally in many countries. The pharmacology, chemistry, pharmacokinetics, pharmacodynamics, efficacy and safety in the Phase II and III clinical trials, safety in the long-term extension studies and postmarketing safety reports are the focus of this review.
27992692 Rheumatoid Arthritis and Risk of Malignant Lymphoma: Is the Risk Still Increased? 2017 Apr OBJECTIVE: Patients with rheumatoid arthritis (RA) are at increased risk of malignant lymphomas with a strong correlation with RA disease severity. Given the changes in RA therapy over recent decades, this study was undertaken to assess whether lymphoma risk remains increased, and if so, to explore risk predictors and lymphoma subtypes. METHODS: We identified 12,656 cases of incident RA in the Swedish Rheumatology Quality Register 1997-2012 and obtained information on therapy and inflammatory activity during the first year after diagnosis. Each patient was matched to 10 population comparator subjects. Through linkage to the Swedish Cancer Register, lymphomas, including subtypes, were identified. We assessed hazard ratios (HRs) using Cox regression. RESULTS: Overall, the HR for lymphoma was increased in RA, to 1.6 (95% confidence interval [95% CI] 1.2-2.1). Taking RA duration into account, risks did not appear to have declined over successive calendar years of RA diagnosis. Neither use of methotrexate the first year after RA diagnosis nor ever use of tumor necrosis factor inhibitors (TNFi) increased lymphoma risk (HR 0.9 [95% CI 0.4-1.9]). Use of oral corticosteroids the first year after RA diagnosis was associated with a reduced risk (HR 0.5 [95% CI 0.3-0.9]). Inflammatory activity during the first year after RA diagnosis did not predict future lymphoma risk. Chronic lymphocytic leukemia occurred less frequently, and Hodgkin's lymphoma occurred more frequently, in RA patients than in the general population. CONCLUSION: The average lymphoma risk in recently diagnosed RA is similar in magnitude to that reported in historical cohorts. Standard antirheumatic treatment including TNFi did not predict future lymphoma risk. Distribution of lymphoma subtypes warrants further investigation.
28952204 Disease activity trajectories in early rheumatoid arthritis following intensive DMARD ther 2017 Oct OBJECTIVE: To identify the disease activity trajectories during intensive triple disease modifying anti-rheumatic drug (DMARD) therapy over 3 years in rheumatoid arthritis (RA) patients and to evaluate the association with treatment persistence. METHODS: Disease Activity Score in 28 joints, baseline risk factors and medication usage were obtained from a longitudinal observational cohort of early RA patients, most of whom were treated with combination DMARD therapy consisting of methotrexate, sulfasalazine and hydroxychloroquine. Persistence of each DMARD was defined as the duration of time from initiation to cessation. A group-based trajectory modelling technique was used to identify disease activity trajectories. RESULT: Three disease activity trajectories (good [43.8%], moderate [39.7%] and poor [16.5%]) were identified in a cohort of 297 patients. Most baseline risk factors, medication usage, the rate of treatment persistence and the effect of persistence on disease activity differed among patients in each of the three trajectories. Although the rate of persistence was higher in the trajectory with a good outcome, the association with persistence was more pronounced among patients who were in the poor outcome trajectory. Persistence with at least two or all three baseline DMARDs was associated with a decrease in disease activity to a broadly similar degree in all trajectories. CONCLUSION: After correction for other baseline prognostic factors, persistence with initial DMARDs contributes to heterogeneity in disease activity trajectory and there was an association between persistence with initial DMARD therapy and lower long-term disease activity.
29252894 Methotrexate-Related Lymphoproliferative Disorder Presenting with Severe Swelling of the E 2017 Jul CASE: A patient with rheumatoid arthritis (RA) who was being treated with methotrexate (MTX) therapy presented with severe swelling of the left elbow. Magnetic resonance imaging showed a tumor-like lesion around the elbow joint. Fluorodeoxyglucose positron emission tomography indicated multiple lesions in the lung and the lymph nodes. An open biopsy of a cervical lymph node was performed, and MTX-related lymphoproliferative disorder (MTX-LPD) was diagnosed. After cessation of the MTX therapy, the elbow swelling regressed, and the patient was in remission of MTX-LPD. CONCLUSION: MTX-LPD should be considered in the differential diagnosis when a patient with RA develops severe joint swelling while on MTX therapy.