Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
29279493 Other Iatrogenic Immunodeficiency-associated Lymphoproliferative Disorder, Hodgkin Type, f 2018 Apr 15 A 59-year-old man with an 18-year history of rheumatoid arthritis who had been treated with steroids, methotrexate, and infliximab presented with a high-grade fever, cervical lymphadenopathy, and hepatosplenomegaly. Epstein-Barr virus (EBV) hepatitis was diagnosed based on the liver histology and EBV antibody titer. The symptoms improved temporarily, but five months later, the fever, skin rash, jaundice, and thrombocytopenia relapsed. Bone marrow and liver biopsies demonstrated infiltration with Reed-Sternberg cells. Based on these findings, the patient was diagnosed with other iatrogenic immunodeficiency-associated lymphoproliferative disorder (OIIA-LPD), Hodgkin lymphoma type. This case followed a rare clinical course, in that acute hepatitis preceded the diagnosis of OIIA-LPD.
30148441 Tocilizumab modulates serum levels of adiponectin and chemerin in patients with rheumatoid 2019 Mar OBJECTIVES: Adipokines play an important role in the pathophysiology of rheumatoid arthritis (RA), provide a link between the disease and overweight, contributing to explain the enhanced cardiovascular (CV) risk and influence the response to disease-modifying anti-rheumatic drugs. The aim of this study was to determine the possible effects of intravenous (IV) tocilizumab (TCZ), an interleukin-6 receptor antagonist, on serum levels of leptin, adiponectin, resistin, visfatin, and chemerin. METHODS: Forty-four RA patients with active disease (DAS28-ESR ≥3.2) were treated with IV TCZ (8 mg/kg) once every 4 weeks for six months: 20 patients received TCZ as monotherapy and 24 in association with methotrexate (MTX). At baseline and monthly, before each infusion, body mass index, DAS28-ESR and Health Assessment Questionnaire (HAQ) were recorded. The laboratory parameters, including the adipokines serum levels were collected at baseline and after six months. RESULTS: At the end of the follow-up, ESR, CRP, DAS28-ESR and HAQ resulted significantly improved in patients received TCZ as monotherapy or combined with MTX. Lipid profile showed only a significant increase of total cholesterol. A significant reduction of chemerin and an increase of adiponectin were observed in the whole population and in the subgroups of the patients analysed (TCZ mono or combined therapy) without any significant correlations with clinical and biochemical parameters. No changes in the leptin and resistin levels were detected. CONCLUSIONS: TCZ is able to regulate serum levels of chemerin and adiponectin in RA patients, independently of the disease treatment response, which contributes to explain the CV safety of TCZ.
29575803 Sustained Response Following Discontinuation of Methotrexate in Patients With Rheumatoid A 2018 Aug OBJECTIVE: To evaluate whether tocilizumab (TCZ) monotherapy is noninferior to treatment with TCZ plus methotrexate (MTX) for maintaining clinical responses in patients with rheumatoid arthritis (RA) in whom low disease activity is achieved with TCZ plus MTX. METHODS: Patients with RA who experienced an inadequate response to MTX received MTX plus TCZ 162 mg subcutaneously. At 24 weeks, patients who achieved a Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) of ≤3.2 were randomized to receive TCZ monotherapy or to continue treatment with TCZ plus MTX until week 52. The primary outcome measure was the comparison of the mean change in the DAS28-ESR from week 24 to week 40 between the TCZ monotherapy and TCZ plus MTX arms (noninferiority margin of 0.6). Secondary outcome measures included worsening of the DAS28-ESR by ≥1.2, achievement of a DAS28-ESR of <2.6 and ≤3.2, and safety and immunogenicity. RESULTS: Among the 718 patients enrolled, 296 were randomized at week 24 to receive TCZ monotherapy (n = 147) or TCZ plus MTX (n = 147). The mean changes in the DAS28-ESR from week 24 to week 40 were 0.46 and 0.14 in the TCZ monotherapy arm and the TCZ plus MTX arm, respectively (weighted difference between the groups, 0.318 [95% confidence interval 0.045, 0.592]); discontinuing MTX in TCZ responders was noninferior to continuing MTX. Safety events were broadly similar between the randomized treatment groups; the most common serious adverse event was infection, which occurred in 2.1% of patients in the TCZ monotherapy group and 2.2% of patients receiving TCZ plus MTX. CONCLUSION: Patients with RA receiving TCZ plus MTX who achieve low disease activity can discontinue MTX without significant worsening of disease activity during the 16 weeks following MTX discontinuation.
29554943 Methotrexate inhibits effects of platelet-derived growth factor and interleukin-1β on rhe 2018 Mar 20 BACKGROUND: A key feature of joints in rheumatoid arthritis (RA) is the formation of hyperplastic destructive pannus tissue, which is orchestrated by activated fibroblast-like synoviocytes (FLS). We have demonstrated that the RA risk gene and tumor suppressor Limb bud and heart development (LBH) regulates cell cycle progression in FLS. Methotrexate (MTX) is the first-line treatment for RA, but its mechanisms of action remain incompletely understood. Here, we studied the effects of MTX on mitogen-induced FLS proliferation and expression of cell cycle regulators in vitro. METHODS: Primary FLS from patients with RA or osteoarthritis were stimulated with the mitogen platelet-derived growth factor (PDGF) and the cytokine interleukin-1β (IL-1β) in the presence or absence of MTX. Cells were then subjected to qPCR for gene expression and cell cycle analysis by flow cytometry. RESULTS: Stimulation with PDGF and IL-1β increased the percentage of FLS in the G2/M phase and shifted the cell morphology to a dendritic shape. These effects were inhibited by MTX. Furthermore, PDGF + IL-1β reduced LBH mRNA expression. However, MTX treatment yielded significantly higher transcript levels of LBH, and of CDKN1A (p21) and TP53 (p53), compared to untreated samples upon mitogen stimulation. The expression of DNA methyltransferase-1 (DNMT1) was also higher in the presence of MTX and there was strong correlation between DNMT1 and LBH expression. CONCLUSIONS: Therapeutic concentrations of MTX abolish the effects of PDGF and IL-1β on tumor suppressor expression and inhibit mitogen-promoted FLS proliferation. These data demonstrate novel and important effects of MTX on pathogenic effector cells in the joint, which might involve epigenetic mechanisms.
29888580 [Treatment of Rheumatoid Arthritis by Bee-venom Acupuncture]. 2018 Apr 25 OBJECTIVE: To study the clinical efficacy and safety of bee-venom acupuncture therapy for rheumatoid arthritis (RA). METHODS: A total of 120 cases of RA patients were randomized into bee-sting acupuncture group (treatment) and western medicine group (control) in accordance with the random number table. The patients of the control group were treated by oral administration of Methotrexate (10 mg, once a week) and Celecoxlb (0.2 g, once a day), and those of the treatment group treated by 5 to 15 bee stings of Ashi-points or acupoints according to different conditions and corporeity, and with the bee-sting retained for about 5 min every time, once every other day. The treatment lasted for 8 weeks. The therapeutic effect was assessed by examining symptoms and signs of the affected joints as morning stiffness duration, swollen/tender joint counts (indexes), handgrip strength, 15 m-walking time, visual analogue scale (VAS), Disease Activity Score including a 28-joint count (DAS 28), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-cyclic citrullinated peptide antibody (ACCPA); and for assessing the safety of bee-venom acupuncture, the patients' responses of fever, enlargement of lymph nodes, regional red and swollen, itching, blood and urine tests for routine were examined. RESULTS: Findings of DAS 28 responses displayed that of the two 60 cases in the control and bee-venom acupuncture groups, 15 and 18 experienced marked improvement, 33 and 32 were effective, 12 and 10 ineffective, with the effective rates being 80% and 83. 33%, respectively. No significant difference was found between the two groups in the effective rate (P>0.05). After the treatment, both groups have witnessed a marked decrease in the levels of morning stiffness duration, arthralgia index, swollen joint count index, joint tenderness index, 15 m walking time, VAS, RF, ESR, CRP and ACCPA, and an obvious increase of handgrip strength relevant to their own levels of pre-treatment in each group (P<0.05). There were no significant differences between the two groups in the abovementioned indexes (P>0.05). The routine blood test, routine urine test, routine stool test, electrocardiogram result, the function of liver and kidney and other security index were within the normal range, without any significant adverse effects found after bee-stinging treatment. CONCLUSION: Bee-venom acupuncture therapy for RA patients is safe and effective, worthy of popularization and application in clinical practice.
29592999 Treatment of refractory rheumatoid pleural effusion with abatacept. 2018 Mar 28 Rheumatoid pleural effusion is generally responsive to corticosteroids, but refractory cases require consideration of second-line therapy. Here we report the case of a 61-year-old man with rheumatoid arthritis (RA) who developed a large right-sided pleural effusion and was successfully treated with abatacept. Thoracocentesis showed a sterile exudate and an elevated adenosine deaminase level. The methotrexate and etanercept used to treat the RA were withheld initially while he underwent a trial of prednisolone 40 mg/day for the pleural effusion. However, the effusion did not respond to this therapy. Thoracoscopic biopsy of the right pleura revealed fibrotic changes with lymphocyte infiltration mainly composed of CD4(+) T cells and B cells but no evidence of malignancy or infection. The patient was started on abatacept and resumed methotrexate. The treatment was effective in our case. Abatacept should be considered as a treatment option in patients with refractory rheumatoid pleural effusion.
29796841 Association of hyperhomocysteinemia with genetic variants in key enzymes of homocysteine m 2018 Aug OBJECTIVES: The study investigated the association between plasma homocysteine, folate and vitamin B12 with 5,10 methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), thymidylate synthase (TYMS 2R → 3R) and methionine synthase (MTR A2756G) polymorphisms and methotrexate (MTX) treatment and toxicity in Tunisian Rheumatoid arthritis (RA) patients. METHODS: A total of 185 patients with RA were included. Homocysteine (Hcy) was assessed by fluorescence polarization immunoassay, and folate and vitamin B12 were measured by chemiluminescence immunoassays. The genetic polymorphisms were analyzed by PCR or PCR-RFLP. Hyperhomocysteinemia (HHC) was considered for Hcy > 15 µmol/L. RESULTS: MTHFR C677T polymorphism was associated with HHC in RA patients (multi-adjusted OR, 95% CI 2.18, [1.07-4.57]; p = 0.031). No association was detected with the remaining polymorphisms. Plasma Hcy, folate, and vitamin B12 did not differ according to each polymorphism, or with MTX treatment or toxicity. However, HHC was more prevalent in patients with than those without MTX toxicity (32.7 vs. 16.7%; p = 0.035). CONCLUSIONS: The MTHFR 677TT genotype is an independent risk factor for HHC in Tunisians RA patients. HHC could be a useful marker of MTX toxicity in RA patients.
30374344 Alpha2beta1 Integrin (VLA-2) Protects Activated Human Effector T Cells From Methotrexate-I 2018 β1 integrins are critical for T cell migration, survival and costimulation. The integrin α2β1, which is a receptor for collagen, also named VLA-2, is a major costimulatory pathway of effector T cells and has been implicated in arthritis pathogenesis. Herein, we have examined its ability to promote methotrexate (MTX) resistance by enhancing effector T cells survival. Our results show that attachment of anti-CD3-activated human polarized Th17 cells to collagen but not to fibronectin or laminin led to a significant reduction of MTX-induced apoptosis. The anti-CD3+collagen-rescued cells still produce significant amounts of IL-17 and IFNγ upon their reactivation indicating that their inflammatory nature is preserved. Mechanistically, we found that the prosurvival role of anti-CD3+collagen involves activation of the MTX transporter ABCC1 (ATP Binding Cassette subfamily C Member 1). Finally, the protective effect of collagen/α2β1 integrin on MTX-induced apoptosis also occurs in memory CD4(+) T cells isolated from rheumatoid arthritis (RA) patients suggesting its clinical relevance. Together these results show that α2β1 integrin promotes MTX resistance of effector T cells, and suggest that it could contribute to the development of MTX resistance that is seen in RA.
29545451 Flares in Patients with Rheumatoid Arthritis after Total Hip and Total Knee Arthroplasty: 2018 May OBJECTIVE: Rates of total knee arthroplasty (TKA) and total hip arthroplasty (THA) remain high for patients with rheumatoid arthritis (RA), who are at risk of flaring after surgery. We aimed to describe rates, characteristics, and risk factors of RA flare within 6 weeks of THA and TKA. METHODS: Patients with RA were recruited prior to elective THA and TKA surgery and prospectively followed. Clinicians evaluated RA clinical characteristics 0-2 weeks before and 6 weeks after surgery. Patients answered questions regarding disease activity including self-reported joint counts and flare status weekly for 6 weeks. Per standard of care, biologics were stopped before surgery, while glucocorticoids and methotrexate (MTX) were typically continued. Multivariable logistic regression was used to identify baseline characteristics associated with postsurgical RA flares. RESULTS: Of 120 patients, the mean age was 62 years and the median RA duration 14.8 years. Ninety-eight (82%) met 2010/1987 American College of Rheumatology/European League Against Rheumatism criteria, 53 (44%) underwent THA (and the rest TKA), and 61 (51%) were taking biologics. By 6 weeks, 75 (63%) had flared. At baseline, flarers had significantly higher disease activity (as measured by the 28-joint Disease Activity Score), erythrocyte sedimentation rate, C-reactive protein, and pain. Numerically more flarers used biologics, but stopping biologics did not predict flares, and continuing MTX was not protective. A higher baseline disease activity predicted flaring by 6 weeks (OR 2.12, p = 0.02). CONCLUSION: Flares are frequent in patients with RA undergoing arthroplasty. Higher baseline disease activity significantly increases the risk. Although more patients stopping biologics flared, this did not independently predict flaring. The effect of early postsurgery flares requires further study.
30362424 [Analysis of the interrelation between immune factors and inflammatory markers, and the co 2018 SOct This review presents relevant information about development and course of chronic heart failure (CHF) associated with rheumatoid arthritis (RA). One of the most discussed issues is the effect of systemic inflammatory process on prognosis of CHF. The review focused on current evidence for significance of this comorbidity in CHF. The diagnostic role of current immune markers, such as galectin 3, pentraxin 3, growth differentiation factor 15, and osteopontin was described. The review discussed the significance of antiinflammatory therapy for prognosis of CHF in the presence of systemic diseases. Possible beneficial effects of the basis therapy for RA on CHF outcomes were assessed. The authors noted a positive prognostic significance of methotrexate for the risk of decompensated CHF.
29148420 The expression of mRNA for peptidylarginine deiminase type 2 and type 4 in bone marrow CD3 2018 Mar OBJECTIVES: Antibodies directed to citrullinated proteins are highly specific for rheumatoid arthritis (RA). Citrullination is catalyzed by peptidylarginine deiminase (PAD) enzymes. The current study examined the mRNA expression of PADI2 and PADI4 in bone marrow (BM) CD34+ cells from RA patients. METHODS: CD34+ cells were purified from BM samples obtained from 48 RA patients and from 30 osteoarthritis (OA) patients during joint operations via aspiration from the iliac crest. The expression of mRNAs for PADI2, PADI4 and Sp1 was examined by quantitative reverse transcription PCR. RESULTS: The expression of mRNA for PADI2 was significantly higher in RA BM CD34+ cells than OA BM CD34+ cells. The expression of mRNAs for PADI4 and Sp1 in RA BM CD34+ cells appeared to be increased compared to OA BM CD34+ cells, although it did not reach the statistical significance. The levels of mRNAs for PADI2, PADI4 and Sp1 were not correlated with serum C-reactive protein or with the administration of methotrexate or oral steroids. Finally, the level of PADI2 mRNA as well as that of PADI4 mRNA was significantly correlated with the level of Sp1 mRNA in RA BM CD34+ cells. CONCLUSIONS: These results indicate that the mRNA expression of PADI2, PADI4 and Sp1 is upregulated in RA BM CD34+ cells independently of the systemic inflammation or treatment regimen. Moreover, the data suggest that the enhanced mRNA expression of PADI2 and PADI4 in BM CD34+ cells might be a result of the enhanced expression of Sp1 gene in RA BM CD34+ cells.
30569216 Inhibition of periarticular bone loss is associated with clinical remission and ACR70-Resp 2019 Apr The aim of this study, based on a post hoc analysis of the data set used in the RAPID 1 trial, focuses on the associations between metacarpal bone mineral density, as estimated by digital X-ray radiogrammetry (DXR), and clinical remission as well as ACR70-Response in rheumatoid arthritis (RA) patients treated with certolizumab pegol (CZP). The trial evaluates a total of 345 RA patients treated with methotrexate versus CZP 200 mg versus CZP 400 mg. All patients underwent X-rays of the hand at baseline and week 52 as well as computerized calculations of bone mineral density (BMD) by DXR. Clinical remission was defined as DAS28 < 2.6. ACR70-Response was also evaluated. The radiological assessment of disease progression was estimated using the modified total Sharp Score. The mean difference for DAS28 was observed for patients treated with CZP 400 mg (median: - 3.53, minimum: - 6.77; maximum: + 0.48) and CZP 200 mg (median: - 3.13, minimum: - 6.37; maximum: - 0.52) compared to the methotrexate group (median - 2.41, minimum: - 4.76; maximum: + 0.31). The DXR-BMD showed a minor bone loss for the treatment groups undergoing therapy with CZP 200 mg (median: - 0.009 g/cm(2), minimum: - 0.059 g/cm(2); maximum: + 0.095 g/cm(2)) and CZP 400 mg (median: - 0.008 g/cm(2), minimum: - 0.064 g/cm(2); maximum: + 0.080 g/cm(2)). The methotrexate group presented an advanced periarticular metacarpal bone loss as measured by DXR-BMD (median: - 0.024 g/cm(2), minimum: - 0.102 g/cm(2); maximum: + 0.057 g/cm(2)). In the case of clinical remission and ACR70-Response, no significant change of the DXR-BMD was observed for both CZP groups. The study highlights that patients treated with CZP show a less accentuated periarticular bone loss as estimated by DXR in comparison to patients with methotrexate plus placebo. In addition, patients with clinical remission and ACR70-Response revealed no periarticular demineralisation.
29545454 A Systematic Review and Metaanalysis of Antirheumatic Drugs and Vaccine Immunogenicity in 2018 Jun OBJECTIVE: Vaccination is a key strategy to reduce infection risk in patients with rheumatoid arthritis (RA) and is advocated in internationally recognized rheumatology society guidelines. The aim was to evaluate to the effect of antirheumatic drugs on influenza and pneumococcal vaccine immunogenicity. METHODS: We conducted a systematic literature review and metaanalysis comparing the humoral response to influenza (pandemic and seasonal trivalent subunit vaccines) and pneumococcal (23-valent pneumococcal polysaccharide vaccine, 7- and 13-valent pneumococcal conjugated vaccines) vaccination in adult patients with RA treated with antirheumatic drugs. Vaccine immunogenicity was assessed by seroprotection rates measured 3 to 6 weeks postimmunization. Risk ratios (RR) and 95% CI were pooled. RESULTS: Nine studies were included in the metaanalysis (7 studies investigating antirheumatic drug exposures and influenza humoral response, 2 studies investigating pneumococcal vaccine response). Influenza vaccine responses to all subunit strains (H1N1, H3N2, B strain) were preserved with methotrexate (MTX) and tumor necrosis factor inhibitor (TNFi) drug exposure. MTX but not TNFi drug exposure was associated with reduced 6B and 23F serotype pneumococcal vaccine response (RR 0.42, 95% CI 0.28-0.63 vs RR 0.98, 95% CI 0.58-1.67); however, limited data were available to draw any firm conclusions. Combination of MTX with tocilizumab or tofacitinib was associated with reduced pneumococcal and influenza vaccine responses. CONCLUSION: Antirheumatic drugs may limit humoral responses to vaccination as evidenced by pneumococcal responses with MTX exposure; however, they are safe and should not preclude immunization against vaccine-preventable disease. Vaccination should be considered in all patients with RA and encouraged as part of routine care. (Systematic review registration number: PROSPERO 2016: CRD42016048093.).
30701887 Association of polymorphisms of HLA-DRB1 and TNF-308 G/A with radiographic joint damage in 2018 May 11 AIM: To clarify the association between HLA-DRB1 and TNFα (-308G>A) genes polymorphism and joint destruction/further progression during 12 months of the follow-up period (FUP) in patients with early (<6 months), active, predominantly antibodies to cyclic citrullinated peptide (ACCP) and rheumatoid factor (RF)-positive rheumatoid arthritis (RA) treated according to "Treat to target" strategy. MATERIALS AND METHODS: The study included 85 patients with early RA and duration of symptoms <6 months. All patients were initially assigned to subcutaneous methotrexate (MTX) with rapid dose escalation to 20-25 mg/week. Combination MTX + biological therapy, mainly adalimumab, was used when MTX was ineffective. Joint destruction was assessed by Sharp-Van der Heijde modification scoring method at baseline and after 12 months FUP. Real time polymerase chain reaction (PCR-RT) was used for TNFα gene polymorphism (-308G>A) genotyping. Low resolution PCR-RT with subsequent sequence-based typing of *04 were performed to study HLA-DRB1 gene polymorphism. The HLA-DRB1*01, *04:01, *04:04, *04:05, *04:08, *10 alleles were categorized as SE+ (Shared Epitope) alleles. RESULTS: As for TNFα gene polymorphism, it was demonstrated that the number of narrowings and total Sharp score values were almost twice as high at baseline in GG genotype carriers as compared to GA genotype carriers (р<0,005, and р<0,004 respectively). Similar association was found after 12mo FUP. The progression of joint destruction, assessed as the change (∆) in the number of erosions, joint space narrowings and the total score, was statistically significantly associated with HLA-DRB1*(SE) genotypes: the carriers of SE (SE+/SE+) double-dose had more advanced progression as compared to (SE+/SE-)/(SE-/SE-) carriers (р<0,028, р<0,019, р<0,035 respectively). CONCLUSION: Our data suggest that HLA-DRB1 (SE+) gene and TNFα (-308G>A) polymorphisms are associated with the progression of radiographic joint destruction in early, active RA patients managed according to "Treat to target" stratagy.
29574517 Impact of switching oral bisphosphonates to denosumab or daily teriparatide on the progres 2018 Jul In biologic-naïve female RA patients, switching oral BPs to DMAb significantly reduced radiographic joint destruction compared to continuing oral BPs or switching to TPTD at 12 months, which were significantly associated with a decrease of a bone resorption marker at 6 months. INTRODUCTION: The aim of this study was to clarify the effects of switching oral bisphosphonates (BPs) to denosumab (DMAb) or daily teriparatide (TPTD) on the progression of radiographic joint destruction in patients with biologic-naïve rheumatoid arthritis (RA). METHODS: A retrospective, case-controlled study involving 90 female RA patients (mean age 68.2 years, 96.7% postmenopausal, disease activity score assessing 28 joints with CRP (DAS28-CRP) 2.4, methotrexate treatment 81.1%, prednisolone treatment 68.9%, and prior BP treatment 44.8 months), who were allocated depending on each patient's and physician's wishes, to (1) the BP-continue group (n = 30), (2) the switch-to-DMAb group (n = 30), or (3) the switch-to-TPTD group (n = 30), was conducted. Patients were retrospectively selected to minimize the difference of possible clinical backgrounds that may affect the joint destruction of RA. The primary endpoint was to clarify the change of the modified total Sharp score (mTSS) from baseline to 12 months. RESULTS: After 12 months, the mean changes of the modified Sharp erosion score were significantly lower in the switch-to-DMAb group (0.2 ± 0.1; mean ± standard error) than in the switch-to-TPTD group (1.3 ± 0.5; P < 0.05), and mTSS was significantly lower in the switch-to-DMAb group (0.3 ± 0.2) than in the BP-continue group (1.0 ± 0.3; P < 0.05) and the switch-to-TPTD group (1.7 ± 0.6; P < 0.05). The logistic regression analysis showed that mTSS changes were significantly associated with the percent changes of TRACP-5b at 6 months (β = 0.30, 95% CI = 0.002-0.016; P < 0.01). CONCLUSIONS: Changes of systemic bone turnover induced by switching BPs to DMAb or TPTD may affect not only systemic bone mass, but also local joint destruction, and its clinical relevance should be considered comprehensively.
30369612 Sacral Stress Fracture Complicated by L5 Radiculopathy in a Patient with Rheumatoid Arthri 2018 Oct A 60-year-old Japanese woman with severe osteoporosis presented with a history of right buttock pain and right lateral lower leg pain in an L5 distribution. She had been treated with methotrexate and methylprednisolone for rheumatoid arthritis (RA) and interstitial pneumonia. Computed tomography demonstrated a sacral stress fracture in the right sacral ala. The right L5 nerve root was compressed by the fracture site. This case is rare in that L5 radiculopathy was complicated by a sacral stress fracture. Clinicians should suspect sacral stress fractures when RA or osteoporosis is present in women who experiences lumbar pain and lumbar radiculopathy.
30293331 [Chinese expert-based consensus for methotrexate in rheumatic diseases]. 2018 Oct 1 To establish the experts consensus on the use of methotrexate in the treatment of rheumatic diseases. A consensus development panel was established. The panel of consensus was composed of 45 experts in rheumatology from the group of Chinese Association of Rheumatology and Immunology Physicians. The consensus development panel developed 7 recommendations, including the clinical status and application principles of methotrexate in the treatment of rheumatoid arthritis, optimal dosage and route, dosage adjustment, monitoring, long-term safety and management in the perioperative period and before/during pregnancy. This consensus was intended to standardize the use of methotrexate in rheumatic diseases and improve the management of rheumatoid arthritis and other rheumatic diseases.
29897007 An Economic Evaluation of Tofacitinib Treatment in Rheumatoid Arthritis After Methotrexate 2018 Oct BACKGROUND: Treatment cycling with biologic disease-modifying anti-rheumatic drugs, such as tumor necrosis factor inhibitors (TNFi), is common among patients with rheumatoid arthritis (RA) and can result in reduced clinical efficacy and increased economic burden. Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. OBJECTIVE: To evaluate and compare the economic effect of tofacitinib 5 mg twice daily (BID) treatment directly after methotrexate (MTX) in the MTX-inadequate responder population, or after MTX and 1 TNFi (adalimumab [ADA] or etanercept [ETN]) or 2 TNFi (ADA and ETN) in TNF-inadequate responder patients with RA, from a U.S. payer perspective. METHODS: A decision-tree economic model was used to evaluate costs over 2 years. Treatment response was modeled as American College of Rheumatology (ACR) 20/50/70 response. ACR response rates at 6-month intervals were derived from U.S. prescribing information for monotherapy and combination therapy. Safety event rates were sourced from a meta-analysis. It was assumed that 75% of patients switched therapy after an adverse event or lack of response. Cost inputs included drugs, monitoring and administration (including physician visits), health care utilization, and treatment for adverse events. The population comprised all organization members (i.e., RA and non-RA members); RA patients receiving TNFi were estimated using epidemiologic data. Results were based on an organization size of 1 million. Economic endpoints were total 2-year costs, costs per member per month (PMPM), and costs per ACR20/50 responder. RESULTS: 1,321 patients were included for analysis. Based on ACR20 switch criteria and either 100% or 50% monotherapy rates for all treatments, total 2-year costs and costs PMPM were lower for patients receiving tofacitinib as second-line therapy after MTX and as third-line therapy after MTX and 1 TNFi; costs were highest for patients who cycled through 2 TNFi. Similar trends were observed for switch criteria based on ACR50 response and addition of 20% rebates for ADA and ETN and 0% for tofacitinib, although differences were mitigated slightly. CONCLUSIONS: A treatment strategy with tofacitinib as either second- or third-line therapy after MTX may be a lower cost treatment option, compared with fourth-line introduction of tofacitinib after cycling through 2 TNFi following MTX. DISCLOSURES: All aspects of this study were funded by Pfizer. Claxton was an employee of York Health Economics Consortium, University of York, at the time of this study. Taylor is an employee of York Health Economics Consortium, The University of York, which received funding from Pfizer to conduct this study. Soonasra, Bourret, and Gerber are employees of Pfizer and hold stock/stock options in Pfizer. A previous iteration of the data reported in this manuscript (before adjustment for recent drug price increases) was presented at the Academy of Managed Care Pharmacy 28th Annual Meeting and Expo; April 19-22, 2016; held in San Francisco, CA.
28970207 Clinical and radiological outcomes of 5-year drug-free remission-steered treatment in pati 2018 Jan OBJECTIVES: To determine the 5-year outcomes of early remission induction therapy followed by targeted treatment aimed at drug-free remission (DFR) in patients with early arthritis. METHODS: In 12 hospitals, 610 patients with early (<2 years) rheumatoid arthritis (RA) or undifferentiated arthritis (UA) started on methotrexate (MTX) 25 mg/week and prednisone (60 mg/day tapered to 7.5 mg/day). Patients not in early remission (Disease Activity Score <1.6 after 4 months) were randomised (single blind) to arm 1, adding hydroxychloroquine 400 mg/day and sulfasalazine 2000 mg/day, or arm 2, switching to MTX plus adalimumab 40 mg/2 weeks. Treatment adjustments over time aimed at DFR. Outcomes were remission percentages, functional ability, toxicity and radiological damage progression after 5 years. RESULTS: After 4 months, 387 patients were in early remission, 83 were randomised to arm 1 and 78 to arm 2. After 5 years, 295/610 (48%) patients were in remission, 26% in sustained DFR (SDFR) (≥1 year) (220/387 (57%) remission and 135/387 (35%) SDFR in the early remission group, 50% remission, 11% SDFR in the randomisation arms without differences between the arms). More patients with UA (37% vs 23% RA, p=0.001) and more anticitrullinated protein antibody (ACPA)-negative patients (37% vs 18% ACPA-positive, p<0.001) achieved SDFR.Overall, mean Health Assessment Questionnaire was 0.6 (0.5), and median (IQR) damage progression was 0.5 (0-2.7) Sharp/van der Heijde points, with only five patients showing progression >25 points in 5 years. CONCLUSIONS: Five years of DFR-steered treatment in patients with early RA resulted in almost normal functional ability without clinically relevant joint damage across treatment groups. Patients who achieved early remission had the best clinical outcomes. There were no differences between the randomisation arms. SDFR is a realistic treatment goal.
29606664 Rheumatoid Arthritis Magnetic Resonance Imaging Score Predicts Therapy Response: Results o 2018 Jun OBJECTIVE: Markers for treatment response in rheumatoid arthritis (RA) are lacking. The aim of the study was to assess the performance of the RA magnetic resonance imaging (MRI) scoring system (RAMRIS) in combination with serum biomarkers to predict response to methotrexate (MTX) treatment in therapy-naive patients with early RA by using high-field MRI. METHODS: Twenty-eight patients with RA were prospectively assessed with baseline 3-T MRI of the clinical dominant hand, 3 and 6 months after MTX. The patients met the 2010 American College of Rheumatology/European League Against Rheumatism (EULAR) criteria [average age 56.8 yrs (range 39-74); positive for rheumatoid factor and/or anticyclic citrullinated peptide antibodies; disease duration < 6 mos (range 2-23 weeks)]. RAMRIS and serum biomarkers consisting of various experimental proteins including receptor activator of nuclear factor-κB ligand (RANKL) were obtained. Remission or treatment response was defined according to EULAR. To adjust for intrapersonal correlation, generalized linear mixed models were used. RESULTS: Treatment response at 3 months was associated to low RAMRIS erosion subscores and low total RAMRIS scores (p = 0.019 and 0.03, respectively). Remission at 6 months was associated to low RANKL levels (p = 0.033). In multivariate analyses, response at 3 and 6 months was predicted more accurately with the inclusion of total RAMRIS score, RAMRIS synovitis subscore at the second metacarpophalangeal (MCP) joint, or a combination of the two (p value likelihood ratio test = 0.035, 0.035, and 0.041, respectively). Remission was more accurately predicted with inclusion of RANKL, with no significant predictive effect of MRI. CONCLUSION: Baseline total RAMRIS can predict EULAR response. RAMRIS synovitis subscore at the second MCP joint and RANKL are associated with response and remission, respectively.