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ID PMID Title PublicationDate abstract
30894208 Sarilumab plus methotrexate in patients with active rheumatoid arthritis and inadequate re 2019 Mar 20 BACKGROUND: Sarilumab is a human immunoglobulin G1 anti-interleukin-6 (IL-6) receptor monoclonal antibody that blocks IL-6 from binding to membrane-bound and soluble IL-6 receptor α. This bridging study assessed the efficacy and safety of sarilumab + methotrexate (MTX) in Japanese patients with active rheumatoid arthritis (RA) and inadequate response to MTX (MTX-IR). METHODS: In this phase III study, 243 patients were randomized 2:2:1:1 to receive subcutaneous sarilumab 150 mg every 2 weeks (q2w), sarilumab 200 mg q2w, placebo switching to sarilumab 150 mg q2w + MTX at 24 weeks, or placebo switching to sarilumab 200 mg q2w at 24 weeks, all in combination with MTX, for a total of 52 weeks (double-blind, placebo-controlled 24-week period followed by a single-blind 28-week extension). The primary endpoint was the proportion of patients achieving American College of Rheumatology 20% improvement criteria (ACR20) responses at week 24. RESULTS: ACR20 response rates at week 24 were 67.9%, 57.5%, and 14.8% for sarilumab 150 mg, sarilumab 200 mg, and placebo, respectively. Serious treatment-emergent adverse events were reported by 9.9%, 6.3%, 0%, and 13.3% of patients in the sarilumab 150 mg, sarilumab 200 mg, placebo to sarilumab 150 mg, and placebo to sarilumab 200 mg groups, respectively. No deaths occurred. The incidence of infections ranged from 52.5 to 67.9%, with five serious infections for the sarilumab 150 mg group and one for the group switched from placebo to 200 mg sarilumab. Absolute neutrophil count < 1.0 Giga/l occurred in 13.6% and 7.5% of patients in the sarilumab 150 and 200 mg groups, respectively, and was not associated with infection. CONCLUSIONS: In Japanese MTX-IR RA patients treated with sarilumab (150 and 200 mg q2w) in combination with MTX, sustained clinical efficacy was shown by significant improvement in signs, symptoms, and physical function; bridging between this and a previous global study was achieved. At week 52, the safety profiles of both doses of sarilumab were generally similar, as previously observed and as expected based on IL-6 class. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02293902 . Registered on 19 November 2014.
31464109 Effectiveness of subcutaneously administered methotrexate in patients with rheumatoid arth 2019 Sep BACKGROUND: Subcutaneous methotrexate (sMTX) administration is considered more effective than the oral route due to better bioavailability and a lower rate of adverse drug reactions (ADRs); however, clinical data supporting this hypothesis is scarce. OBJECTIVES: The aim of the study was to evaluate the efficacy and tolerability of sMTX in patients with active rheumatoid arthritis (RA), including a subset classified as an early stage of RA. MATERIAL AND METHODS: A post-marketing, multicenter, open-label, non-randomized, non-interventional study enrolled 771 adult patients with active RA treated with sMTX (Metex®) for 2-6 weeks. The evaluation of therapy effectiveness (DAS28-ESR or DAS28-CRP) and monitoring of ADRs was an element of routine patient management. Therapy effectiveness was scored as the achievement of remission or response (according to European League Against Rheumatism (EULAR)). RESULTS: Among 761 (98.7%) patients that continued sMTX (after 25-31 weeks), clinical response was achieved by 69.5%, remission by 19.2% and low disease activity by 34.2%. Patients aged >60 years were less likely to achieve both remission (odds ratio (OR) = 0.61 (95% confidence interval (95% CI) = 0.39-0.93)) and clinical response (OR = 0.82 (95% CI = 0.71-0.95)), while overweight/obese patients (OR = 1.11 (95% CI = 1.00-1.24)) and those with early RA had greater chance to reach a clinical response (OR = 1.18 (95% CI = 1.03-1.34)). There were 16 ADRs (no serious or severe). In addition, at least 2-fold increase in alanine transaminase (ALT) activity was noted in 10 patients (1.3%). CONCLUSIONS: After 6-month therapy with sMTX, about 70% of patients with RA achieve a clinical response, and remission was observed in 20%. Younger age, overweight/obesity and an early stage of the disease are factors increasing therapy effectiveness; sMTX is well tolerated.
31544222 A case of denosumab-associated membranous nephropathy in a patient with rheumatoid arthrit 2020 Feb We herein report a case of anti-RANKL monoclonal antibody-associated membranous nephropathy (MN). A 67-year-old woman with a history of rheumatoid arthritis treated with prednisolone and methotrexate for more than 30 years and osteoporosis treated with eldecalcitol and teriparatide for 4 years had achieved a stable disease condition. Her kidney function was normal and her urinalysis was negative for hematuria and proteinuria. An anti-RANKL monoclonal antibody (denosumab) was administered for the treatment of osteoporosis. Four months later, proteinuria appeared (2.3 g/g creatinine) and remained positive for about 6 months, therefore, she was admitted to our hospital. An immunofluorescence study revealed fine granular deposits of immunoglobulin G (IgG) and C3 along the capillary walls. Staining for IgG subclasses showed positive staining for IgG1 (3+), IgG2 (1+), IgG3 (1+), and IgG4 (1+); phospholipase A2 receptor was negative. Electron microscopy showed partial subepithelial and intramembranous deposits and focal thickening of the glomerular basement membrane. No evidence of malignancy or infectious disease was seen. After cessation of denosumab, the proteinuria gradually improved. Based on the renal biopsy results and clinical course (development of marked proteinuria in the presence of denosumab with subsequent amelioration in the absence of the drug), we diagnosed the patient with secondary MN due to denosumab. This is the first reported case of denosumab-associated MN.
29939099 Combination effect of anti-rheumatic medications for coronary artery diseases risk in rheu 2019 Feb OBJECTIVES: To determine whether a combination of anti-rheumatic drugs is associated with the risk of coronary artery diseases (CAD) in incident rheumatoid arthritis (RA) patients. METHODS: This population-based cohort study used administrative data to identify 6260 newly-diagnosed patients with RA (age ≥20 years) as the study group. The study end-point was occurrence of CAD according to the ICD-9-CM codes. Exposure to different combinations of drugs and the risk of CAD was assessed. These included different combinatiosn of celecoxib (Cx), hydroxychloroquine (HCQ), methotrexate (MTX), and sulfasalazine (SSZ). Patients who never used Cx, HCQ, MTX, or SSZ were used as a reference group. A Cox proportional hazards model was used to estimate the hazard ratio (HR) of disease after controlling for demographic and other co-morbidities. When the proportionality assumption was violated, the spline curve of the Scaled Schoenfeld residuals was fitted to demonstrate the estimated effect on CAD over time for drug usage. RESULTS: Among RA patients, the adjusted HR (95% confidence interval) of CAD for "Cx only", "Cx and HCQ ever", and "Cx, HCQ, MTX, and SSZ ever", were 0.29 (0.19-0.44), 0.46 (0.24-0.88), and 0.42 (0.24- 0.75), respectively, during the first period of 0-3, 4, or 7 years. However, they became 1.04 (0.78-1.38), 1.16 (0.62-2.19), and 0.59 (0.32-1.08), respectively, during the second time period of 3, 4, or 7-10 years. The adjusted HR (95% CI) of CAD for "Cx, MTX, and SSZ ever" remains constant at 0.12 (0.02-0.89). CONCLUSIONS: Celecoxib-DMARDs drug combinations were associated with reduced CAD risk on incident RA patients, and some of them exhibited the time-varying drug effect.
31276602 Optimising low-dose methotrexate for rheumatoid arthritis-A review. 2019 Oct Methotrexate at low doses (5-25 mg/week) is first-line therapy for rheumatoid arthritis. However, there is inter- and intrapatient variability in response, with contribution of variability in concentrations of active polyglutamate metabolites, associated with clinical efficacy and toxicity. Prescribing remains heterogeneous across population groups, disease states and regimens. This review examines current knowledge of dose-response of oral methotrexate in the setting of rheumatoid arthritis, and how this could help inform dosage regimens.
31243219 Simultaneous Presentation of Lymphomatoid Granulomatosis and Multiple myeloma in an Immuno 2019 Oct 1 A 75-year-old Japanese woman with a 20-year history of rheumatoid arthritis presented with symptomatic bilateral pleural effusion and lung and brain tumors. She had received methotrexate for five years and tacrolimus for one year. A brain biopsy specimen showed the pathological features of lymphoproliferative disease, but a bone marrow biopsy showed proliferation of plasma cells. She was finally diagnosed with coexistent lymphomatoid granulomatosis (LYG) of the brain and lung and multiple myeloma (MM) of the bone marrow and received chemotherapy for both. This report shows that immunodeficient patients are at risk of developing the unusual coexistence of LYG and MM.
30643209 CP-25 reverses prostaglandin E4 receptor desensitization-induced fibroblast-like synoviocy 2019 Aug Paeoniflorin-6'-O-benzene sulfonate (CP-25) is a novel compound derived from paeoniflorin that has been demonstrated to have therapeutic effects in a rat model of rheumatoid arthritis (RA). However, the underlying mechanism has not been elucidated to date. We explored this mechanism in the present study by treating rats with adjuvant arthritis (AA) with CP-25. We found that the membrane EP4 protein level was downregulated; whereas, GRK2 was upregulated, in fibroblast-like synoviocyte (FLS)s of AA rats. Prostaglandin (PGE)2 stimulated FLS proliferation and enhanced the membrane EP4 receptor protein level; the latter was reversed by the administration of an EP4 receptor agonist, whereas the membrane GRK2 protein level gradually increased. The changes in the EP4 receptor and GRK2 expression were enhanced by TNF-α, and the former was accompanied by an alteration in the cyclic (c)AMP level. The EP4 receptor agonist stimulation increased the association between GRK2 and the EP4 receptor. GRK2 knockdown abrogated the abnormalities in FLS proliferation. The CP-25 treatment (100 mg/kg) suppressed joint inflammation with an efficacy that was similar to that of methotrexate. This finding was associated with EP4 upregulation and GRK2 downregulation in FLSs. Thus, GRK2 plays an important role in the abnormal FLS proliferation observed in AA possibly by promoting EP4 receptor desensitization and decreasing the cAMP level. Our results demonstrate that CP-25 has therapeutic potential for the treatment of human RA via GRK2 regulation.
30712241 FKB327: An Adalimumab Biosimilar. 2019 Feb FKB327 (Hulio(®)) is a biosimilar of the reference monoclonal anti-TNFα antibody adalimumab, and is approved in the EU for use in the same indications as reference adalimumab. FKB327 has similar physicochemical and pharmacodynamic properties to those of reference adalimumab, and pharmacokinetic equivalence was shown in healthy volunteers and patients with moderate-to-severe rheumatoid arthritis (RA) despite methotrexate therapy. FKB327 demonstrated equivalent clinical efficacy to that of reference adalimumab in patients with moderate-to-severe RA, and similar tolerability, safety and immunogenicity profiles. Switching from reference adalimumab to FKB327 had no impact on efficacy, safety or immunogenicity.
31674342 Nuclear Factor kappa B (NF-κB) Targeted Self-Assembled Nanoparticles Loaded with Methotre 2019 Nov 1 BACKGROUND Nanotechnology is one of the most productive approaches for specifically delivering drug payloads to the region of interest to decrease nonspecific distribution and unwanted toxicities. MATERIAL AND METHODS We prepared glycol chitosan stearate self-assembled nanoparticles loaded with methotrexate (MTX) for NF-kappaB targeting in treatment of rheumatoid arthritis (RA). The nanoparticles were prepared using hydrophobic modification of glycol chitosan (GC) with steric acid (SA) and was characterized using IR. The efficiency of nanoparticles after their physiochemical characterization was measured in vitro and by in vivo studies in mice. RESULTS The nanoparticles thus prepared were spherical in shape, 235 nm in diameter, and had negative zeta potential. The entrapment efficiency of MTX-GC-SA was more than 70%. The in vitro higher uptake of MTX-GC-SA in murine macrophage cells (RAW 264.7) was confirmed using confocal microscopy and FACS analysis. Systemic administration of MTX-GC-SA into collagen-induced arthritis (CIA) mice resulted in high accumulation in inflamed joints. The MTX-GS-SA revealed significantly better therapeutic efficacy against CIA mice compared to free MTX. CONCLUSIONS These findings highlight the potential of using this MTX-GC-SA nanoparticle formulation in suppressing inflammatory arthritis for effective treatment of RA.
31388915 Comparative Effectiveness of Combining MTX with Biologic Drug Therapy Versus Either MTX or 2019 Oct BACKGROUND: Comparative effectiveness of early rheumatoid arthritis (RA) treatments remains uncertain. PURPOSE: Compare benefits and harms of biologic drug therapies for adults with early RA within 1 year of diagnosis. DATA SOURCES: English language articles from the 2012 review to October 2017 identified through MEDLINE, Cochrane Library and International Pharmaceutical Abstracts, gray literature, expert recommendations, reference lists of published literature, and supplemental evidence data requests. STUDY SELECTION: Two persons independently selected studies based on predefined inclusion criteria. DATA EXTRACTION: One reviewer extracted data; a second reviewer checked accuracy. Two independent reviewers assigned risk of bias ratings. DATA SYNTHESIS: We identified 22 eligible studies with 9934 participants. Combination therapy with tumor necrosis factor (TNF) or non-TNF biologics plus methotrexate (MTX) improved disease control, remission, and functional capacity compared with monotherapy of either MTX or a biologic. Network meta-analyses found higher ACR50 response (50% improvement) for combination therapy of biologic plus MTX than for MTX monotherapy (relative risk range 1.20 [95% confidence interval (CI), 1.04 to 1.38] to 1.57 [95% CI, 1.30 to 1.88]). No significant differences emerged between treatment discontinuation rates because of adverse events or serious adverse events. Subgroup data (disease activity, prior therapy, demographics, serious conditions) were limited. LIMITATIONS: Trials enrolled almost exclusively selected populations with high disease activity. Network meta-analyses were derived from indirect comparisons relative to MTX due to the dearth of head-to-head studies comparing interventions. No eligible data on biosimilars were found. CONCLUSIONS: Qualitative and network meta-analyses suggest that the combination of MTX with TNF or non-TNF biologics reduces disease activity and improves remission when compared with MTX monotherapy. Overall adverse event and discontinuation rates were similar between treatment groups. REGISTRATION: PROSPERO (available at http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42017079260 ).
31484893 [Methotrexate-associated lymphoproliferative disorders: clinical aspects]. 2019 Methotrexate-associated lymphoproliferative disorders (MTX-LPD) is categorized into other iatrogenic immunodeficiency-associated lymphoproliferative disorders, developing LPD in patients with autoimmune diseases (AIDs) under low dose MTX administration. Two-thirds of MTX-LPDs regresses after MTX withdrawal with the higher incidence in Japanese patients, MTX-LPDs consist of various subtypes of LPDs, the feature of each LPD such as the regressive rate, relapse/regrowth rate, and prognosis, widely varies. The absolute lymphocyte count (ALC) in peripheral blood is suggested to influence LPD development, regression, and relapse/regrowth events. Because various factors might effect the pathogenesis and clinical features of MTX-LPD, careful attention should be paid to assess MTX-LPD.
30729592 Synergistic enhancement and hepatoprotective effect of combination of total phenolic extra 2019 Apr Rheumatoid arthritis (RA) is an autoimmune inflammatory disorder characterized by joint destruction and bone damage. Methotrexate (MTX) is recommended as the first-line disease-modifying agent for the treatment of RA. However, the clinical efficacy of MTX is limited due to its low response and side effects, especially hepatotoxicity. Total phenolic extracts of Citrus aurantium L. (TPE-CA) are rich in dietary bioactive flavonoids, which show beneficial effects on liver health and are regarded as therapeutic tools against inflammatory diseases. In this study, the efficacy of MTX, alone or in combination with TPE-CA, for the treatment of collagen-induced arthritis and protection against hepatic injury in rats was investigated. TPE-CA and MTX combination effectively reduced the inflammatory symptoms and joint damage by inhibiting the NF-κB pathway. Moreover, TPE-CA significantly ameliorated MTX-induced chronic hepatic injury by enhancing antioxidant enzymes activities, suppressing hepatic cytochrome P450 2E1 expression, and modulating the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway. This combination regimen not only provided synergistic enhancement but also exhibited hepatoprotective effect against chemically induced chronic hepatotoxicity. This could be an alternative strategy to improve the low response of MTX in RA treatment.
31630117 Sustained discontinuation of infliximab with a raising-dose strategy after obtaining remis 2020 Jan OBJECTIVES: The aim of this study is to determine whether the 'programmed' infliximab (IFX) treatment strategy (for which the dose of IFX was adjusted based on the baseline serum tumour necrosis factor α (TNF-α)) is beneficial to induction of clinical remission after 54 weeks and sustained discontinuation of IFX for 1 year. METHODS: In this multicentre randomised trial, patients with IFX-naïve rheumatoid arthritis with inadequate response to methotrexate were randomised to two groups; patients in programmed treatment group received 3 mg/kg IFX until week 6 and after 14 weeks the dose of IFX was adjusted based on the baseline levels of serum TNF-α until week 54; patients in the standard treatment group received 3 mg/kg of IFX. Patients who achieved a simplified disease activity index (SDAI) ≤3.3 at week 54 discontinued IFX. The primary endpoint was the proportion of patients who sustained discontinuation of IFX at week 106. RESULTS: A total of 337 patients were randomised. At week 54, 39.4% (67/170) in the programmed group and 32.3% (54/167) in the standard group attained remission (SDAI ≤3.3). At week 106, the 1-year sustained discontinuation rate was not significantly different between two groups; the programmed group 23.5% (40/170) and the standard group 21.6% (36/167), respectively (2.2% difference, 95% CI -6.6% to 11.0%; p=0.631). Baseline SDAI <26.0 was a statistically significant predictor of the successfully sustained discontinuation of IFX at week 106. CONCLUSION: Programmed treatment strategy did not statistically increase the sustained remission rate after 1 year discontinuation of IFX treatment.
31064384 Does treatment strategy influence the ability to achieve and sustain DMARD-free remission 2019 May 7 OBJECTIVES: To study the impact of treatment strategy on achieving and sustaining disease-modifying antirheumatic drug (DMARD)-free remission in patients with rheumatoid arthritis (RA). METHODS: Two hundred seventy-nine RA patients (median follow-up 7.8 years) were studied. Of these, 155 patients participated in a disease activity score (DAS) < 1.6 steered trial aimed at DMARD-free remission. Initial treatment comprised methotrexate with high-dose prednisone (60 mg/day) and a possibility to start biologicals after 4 months. In the same period and hospital, 124 patients were treated according to routine care, comprising DAS < 2.4 steered treatment. Percentages of DMARD-free remission (absence of synovitis for ≥ 1 year after DMARD cessation), late flares (recurrence of clinical synovitis ≥ 1 year after DMARD cessation), and DMARD-free sustained remission (DMARD-free remission sustained during complete follow-up) were compared between both treatment strategies. RESULTS: Patients receiving intensive treatment were younger and more often ACPA-positive. On a group level, there was no significant association between intensive treatment and DMARD-free remission (35% vs 29%, corrected hazard ratio (HR) 1.4, 95%CI 0.9-2.2), nor in ACPA-negative RA (49% versus 44%). In ACPA-positive RA intensive treatment resulted in more DMARD-free remission (25% vs 6%, corrected HR 4.9, 95%CI 1.4-17). Intensive treatment was associated with more late flares (20% versus 8%, HR 2.3, 95%CI 0.6-8.3). Subsequently, there was no difference in DMARD-free sustained remission on a group level (28% versus 27%), nor in the ACPA-negative (43% versus 42%) or ACPA-positive stratum (17% versus 6%, corrected HR 3.1, 95%CI 0.9-11). CONCLUSIONS: Intensive treatment did not result in more DMARD-free sustained remission, compared to routine up-to-date care. The data showed a tendency towards an effect of intensive treatment in ACPA-positive RA; this needs further investigation.
31004324 Economic Evaluation of Sarilumab in the Treatment of Adult Patients with Moderately-to-Sev 2019 Jun INTRODUCTION: Assess the cost-effectiveness (US healthcare payer perspective) of sarilumab subcutaneous (SC) 200 mg + methotrexate versus conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) or targeted DMARD + methotrexate for moderate-to-severe rheumatoid arthritis (RA) in adults with inadequate response to methotrexate. METHODS: Microsimulation based on patient profiles from MOBILITY (NCT01061736) was conducted via a 6-month decision tree and lifetime Markov model with 6-monthly cycles. Treatment response at 6 months was informed by a network meta-analysis and based on American College of Rheumatology (ACR) response. Responders: patients with ACR20 response who continued with therapy; non-responders: ACR20 non-responders who transitioned to the subsequent treatment. Utilities and quality-adjusted life-years (QALYs) were estimated via mapping 6-month ACR20/50/70 response to relative change in Health Assessment Questionnaire Disability Index score (short term) and based on published algorithms (long term). Direct costs considered drugs (wholesale acquisition costs), administration and routine care. RESULTS: Lifetime QALYs and costs for treatment sequences on the efficiency frontier were 3.43 and $115,019 for active csDMARD, 5.79 and $430,918 for sarilumab, and 5.94 and $524,832 for etanercept (all others dominated). Sarilumab was cost-effective versus tocilizumab and csDMARD (incremental cost-effectiveness ratios of $84,079/QALY and $134,286/QALY). Probabilistic sensitivity analysis suggested comparable costs and slightly improved health benefits for sarilumab versus tocilizumab, irrespective of threshold. CONCLUSION: In patients with moderate-to-severe RA, sarilumab 200 mg SC every 2 weeks + methotrexate can be considered a cost-effective treatment option, with lower costs and greater health benefits than alternative treatment sequences (+ methotrexate) beginning with adalimumab, certolizumab, golimumab and tofacitinib and below commonly accepted cost-effectiveness thresholds against tocilizumab + methotrexate or csDMARD active treatment. FUNDING: Sanofi and Regeneron Pharmaceuticals, Inc.
30526810 Risk of malignant lymphoma in patients with rheumatoid arthritis treated with biological d 2019 Feb OBJECTIVE: This study investigated whether using biological disease-modifying antirheumatic drugs (bDMARDs) further increases the risk of malignant lymphoma in patients with rheumatoid arthritis undergoing methotrexate therapy using spontaneous adverse reaction databases in different countries. MATERIALS AND METHODS: Patient data were acquired from the US Food and Drug Administration's Adverse Event Reporting System (FAERS), the Japanese Adverse Drug Event Report (JADER), and the Canada Vigilance Adverse Reaction Online Database (CVARD) from the first quarter of 2004 to the end of 2015. Data subset analysis was performed to investigate whether the use of bDMARDs further increased the risk of malignant lymphoma in patients receiving methotrexate therapy. RESULTS: The FAERS subset data indicated a significant association between Hodgkin lymphoma and methotrexate with infliximab (reporting odds ratio (ROR): 8.28. 95% CI: 5.70 - 12.02; information component (IC): 2.04, 95% CI: 1.59 - 2.49). In addition, signal scores suggested that methotrexate with infliximab (ROR: 3.26. 95% CI: 2.68 - 3.98; IC: 1.31, 95% CI: 1.04 - 1.58) was significantly associated with non-Hodgkin lymphoma (NHL). The CVARD subset data also indicated a significant association between NHL and methotrexate with infliximab (ROR: 22.82. 95% CI: 5.02 - 103.78; IC: 1.77, 95% CI: 0.13 - 3.41). However, the JADER subset data revealed no significant associations. CONCLUSION: The present study shows that using infliximab further increases the risk of malignant lymphoma in patients receiving methotrexate therapy.
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30701346 Hydroxychloroquine is a safe and effective steroid-sparing agent for immune checkpoint inh 2019 May Immunotherapy for cancer treatment continues to evolve, and immune checkpoints have proven successful therapeutic targets. With success has come the challenge of managing the commonly associated immune-related toxicities. Arthralgias and arthritis are a common immune-related adverse event (IrAE), well described in the literature (Pardoll Nat Rev Cancer 12:252-264, 2012; Diesendruck and Benhar Drug Resist Updat 30:39-47, 2017; Cappelli et al. Arthritis Care Res 69:1751-1763, 2017; Brahmer et al. J Clin Oncol 36:1714-1768, 2018; Smith and Bass (2017). The optimal management of immune checkpoint inhibitor (ICI)-induced arthritis remains unclear. We describe the first series using hydroxychloroquine as a first-line disease-modifying antirheumatic drug (DMARD) for patients without pre-existing autoimmune disease, who developed arthritis secondary to ICI's. This was a single-center retrospective observational study reporting all patients evaluated by rheumatologists affiliated with the University of Alberta, a large tertiary health care center in Northern Alberta, Canada, deemed to have inflammatory arthritis (IA) following ICIs. We identified 11 patients, without pre-existing autoimmune disease, who developed IA following ICIs. Most patients presented with a symmetrical polyarthritis with both large and small joint involvement. All patients were treated according to the outlined treatment protocol with hydroxychloroquine as a first-line steroid-sparing agent: either as monotherapy or in combination with tapering doses of systemic corticosteroids (3) or intra-articular steroid injections (6). One patient required the addition of methotrexate to control symptoms and none required biologic therapy. There were no reported adverse effects from hydroxychloroquine. Inflammatory arthritis is an important complication of ICIs leading to significant impact on patient quality of life. In our experience, in patients without pre-existing autoimmune disease, hydroxychloroquine is an effective first-line therapy for IA secondary to ICI therapy.
30357484 Tocilizumab-induced psoriasis-like eruption resolved by shortening the dose interval in a 2019 Jan Tocilizumab (TCZ) is a humanized antihuman interleukin-6 (IL-6) receptor antibody used for the treatment of inflammatory diseases such as rheumatoid arthritis (RA). While TCZ could act as a therapeutic agent, it has a potential for inducing adverse drug events including psoriasis-like eruption. Seven cases with specific reference to TCZ-induced psoriasis eruption have been reported worldwide so far. In these cases, treatments with the same dosage of TCZ were either maintained or discontinued. Herein, we report a case involving a 74-year-old man diagnosed with rheumatoid factor-positive and anti-citrullinated protein antibody-positive RA with comorbidity of atopic dermatitis. TCZ was administered intravenously with oral methotrexate. After the third infusion, the patient developed TCZ-induced psoriasis-like eruptions, which were resolved by shortening the dose interval. Eruption recurrence was not observed after frequent TCZ subcutaneous injection. Our case may help physicians manage TCZ-induced psoriasis-like eruption.
31396834 Safety of adalimumab biosimilar MSB11022 (acetate-buffered formulation) in patients with m 2019 Dec OBJECTIVES: To compare the safety, efficacy, and immunogenicity of MSB11022 (acetate-buffered formulation), an adalimumab biosimilar, with the reference product. METHOD: AURIEL-RA study was a phase 3, multicenter, randomized, double-blind, parallel group trial (NCT03052322). Patients with moderately-to-severely active rheumatoid arthritis (RA) with an inadequate response to methotrexate were randomized 1:1 to MSB11022 or reference adalimumab. The primary endpoint was the incidence of treatment-emergent adverse events of special interest (AESIs) (predefined as hypersensitivity) up to week 52. The key secondary endpoint was ACR20 (≥ 20% improvement in American College of Rheumatology core set measurements from baseline) at week 12. Other efficacy endpoints, quality of life, immunogenicity, and pharmacokinetic parameters were evaluated up to week 52. Secondary safety endpoints were evaluated up to week 52 and at a 4-month safety follow-up. RESULTS: In total, 288 patients were randomized. The proportion of patients experiencing ≥ 1 treatment-emergent AESI up to week 52 was similar between trial arms: 6 patients (4.2%; 95% CI 1.56, 8.91) receiving MSB11022, and 8 patients (5.5%; 95% CI 2.41, 10.58) receiving reference adalimumab. No clinically meaningful differences in efficacy, quality of life, or immunogenicity were seen between treatment arms up to week 52. No notable difference in the incidence of treatment-emergent adverse events was observed between treatment arms up to the end of the follow-up period. CONCLUSIONS: These results suggest MSB11022 and reference adalimumab are similar in patients with moderately-to-severely active rheumatoid arthritis in terms of safety, immunogenicity, and efficacy. AURIEL-RA provides evidence to support the similarity of MSB11022 and adalimumab.Key Points• Incidences of hypersensitivity events were similar for MSB11022 (modified buffer) and reference adalimumab.• There was no difference in local reactions between MSB11022 (modified buffer) and reference adalimumab.• AURIEL-RA confirms the equivalence in efficacy and immunogenicity of MSB11022 (modified buffer) and reference adalimumab.
30057321 Prophylactic effect of sulfasalazine against Pneumocystis pneumonia in patients with rheum 2019 Feb OBJECTIVES: To evaluate the prophylactic effect of sulfasalazine against Pneumocystis jirovecii pneumonia (PJP) among rheumatoid arthritis (RA) patients. METHODS: We used a nationwide Japanese multicenter RA database to extract data from 2005 and 2014. To identify PJP cases, we selected patients hospitalized for PJP and verified their diagnosis. Two control groups, one unmatched and the other matched for age, sex, glucocorticoid, methotrexate, and tacrolimus dosage, and the use (and type, if used) of biological disease-modifying antirheumatic drug were selected by incidence-density sampling. The odds ratios for PJP associated with sulfasalazine use and other clinical factors were estimated by exact and standard conditional logistic regression. RESULTS: From 18,668 participants, 60 cases, 356 unmatched controls, and 337 matched controls were selected. None of the cases received sulfasalazine before PJP onset. A comparison of the cases with the unmatched controls showed that sulfasalazine use carried a decreased risk of PJP (adjusted odds ratio 0.18, 95% confidence interval 0.00-0.92). A comparison of the cases and matched controls also showed that sulfasalazine use had a decreased risk of PJP (0.08, 0.00-0.36). In an analysis of the cases and unmatched controls who did not receive sulfasalazine, an increased risk of PJP was associated with lung disease (3.88, 1.89-7.95) and the use of glucocorticoid (5.71, 2.68-12.19), methotrexate (5.25, 2.01-13.74), and tumor necrosis factor inhibitors (2.32, 1.10-4.93). CONCLUSIONS: The results of this nested case-control study demonstrated the preventive effect of sulfasalazine against PJP. The results await confirmation by future prospective studies.