Targeting inflammatory pathways in axial spondyloarthritis.

The triggers and pathogenesis of axial spondyloarthritis (axSpA) are not yet completely understood. However, therapeutic agents targeting tumor necrosis factor-α and interleukin-17 inflammatory pathways have proven successful in suppressing many of the clinical symptoms and signs of axSpA, giving us an indication of which pathways are responsible for initiating and maintaining the inflammation. The mechanisms that eventuate in syndesmophytes and ankyloses are less clear. This review addresses these two critical pathways of inflammation, discussing their nature and these factors that may activate or enhance the pathways in patients with axSpA. In addition, genetic and other markers important to the inflammatory pathways implicated in axSpA are explored, and prognostic biomarkers are discussed. Treatment options available for the management of axSpA and their associated targets are highlighted

Risk of serious adverse effects of biological and targeted drugs in patients with rheumatoid arthritis: a systematic review meta-analysis

OBJECTIVES: To determine possible differences in serious adverse effects among the 10 currently approved biological and targeted synthetic DMARDs (b/ts-DMARDs) for RA.METHODS: Systematic review in bibliographic databases, trial registries and websites of regulatory agencies identified randomized trials of approved b/ts-DMARDs for RA. Network meta-analyses using mixed-effects Poisson regression models were conducted to calculate rate ratios for serious adverse events (SAEs) and deaths between each of the 10 drugs and control (i.e. no b/ts-DMARD treatment), based on subjects experiencing an event in relation to person-years. Confidence in the estimates was assessed by applying the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE).RESULTS: A total of 117 trials (47 615 patients) were included. SAEs were more common with certolizumab compared with abatacept (rate ratio = 1.58, 95% CI: 1.18, 2.14), adalimumab (1.36, 95% CI: 1.02, 1.81), etanercept (1.60, 95% CI: 1.18, 2.17), golimumab (1.45, 95% CI: 1.00, 2.08), rituximab (1.63, 95% CI: 1.16, 2.30), tofacitinib (1.44, 95% CI: 1.03, 2.02) and control (1.45, 95% CI: 1.13, 1.87); and tocilizumab compared with abatacept (1.30, 95% CI: 1.03, 1.65), etanercept (1.31, 95% CI: 1.04, 1.67) and rituximab (1.34, 95% CI: 1.01, 1.78). No other comparisons were statistically significant. Accounting for study duration confirmed our findings for up to 6 months' treatment but not for longer-term treatment (6-24 months). No differences in mortality between b/ts-DMARDs and control were found. Based on the GRADE approach, confidence in the estimates was low due to lack of head-to-head comparison trials and imprecision in indirect estimates.CONCLUSION: Despite low confidence in the estimates, our analysis found potential differences in rates of SAEs. Our data suggest caution should be taken when deciding among available drugs. OBJECTIVES: To determine possible differences in serious adverse effects among the 10 currently approved biological and targeted synthetic DMARDs (b/ts-DMARDs) for RA.METHODS: Systematic review in bibliographic databases, trial registries and websites of regulatory agencies identified randomized trials of approved b/ts-DMARDs for RA. Network meta-analyses using mixed-effects Poisson regression models were conducted to calculate rate ratios for serious adverse events (SAEs) and deaths between each of the 10 drugs and control (i.e. no b/ts-DMARD treatment), based on subjects experiencing an event in relation to person-years. Confidence in the estimates was assessed by applying the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE).RESULTS: A total of 117 trials (47 615 patients) were included. SAEs were more common with certolizumab compared with abatacept (rate ratio = 1.58, 95% CI: 1.18, 2.14), adalimumab (1.36, 95% CI: 1.02, 1.81), etanercept (1.60, 95% CI: 1.18, 2.17), golimumab (1.45, 95% CI: 1.00, 2.08), rituximab (1.63, 95% CI: 1.16, 2.30), tofacitinib (1.44, 95% CI: 1.03, 2.02) and control (1.45, 95% CI: 1.13, 1.87); and tocilizumab compared with abatacept (1.30, 95% CI: 1.03, 1.65), etanercept (1.31, 95% CI: 1.04, 1.67) and rituximab (1.34, 95% CI: 1.01, 1.78). No other comparisons were statistically significant. Accounting for study duration confirmed our findings for up to 6 months' treatment but not for longer-term treatment (6-24 months). No differences in mortality between b/ts-DMARDs and control were found. Based on the GRADE approach, confidence in the estimates was low due to lack of head-to-head comparison trials and imprecision in indirect estimates.CONCLUSION: Despite low confidence in the estimates, our analysis found potential differences in rates of SAEs. Our data suggest caution should be taken when deciding among available drugs.SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42014014842

Repository Corticotropin Injection for Active Rheumatoid Arthritis Despite Aggressive Treatment: A Randomized Controlled Withdrawal Trial.

INTRODUCTION: The objective of this study was to assess efficacy and safety of repository corticotropin injection (RCI) in subjects with active rheumatoid arthritis (RA) despite treatment with a corticosteroid and one or two disease-modifying antirheumatic drugs (DMARDs). METHODS: All subjects received open-label RCI (80 U) twice weekly for 12 weeks (part 1); only those with low disease activity [LDA; i.e., Disease Activity Score 28 joint count and erythrocyte sedimentation rate (DAS28-ESR) \u3c 3.2] were randomly assigned to receive either RCI (80 U) or placebo twice weekly during the 12-week double-blind period (part 2). The primary efficacy endpoint was the proportion of subjects who achieved LDA at week 12. Secondary efficacy endpoints included proportions of subjects who maintained LDA during weeks 12 through 24 and achieved Clinical Disease Activity Index (CDAI) ≤ 10 at weeks 12 and 24. Safety was assessed via adverse event reports. RESULTS: Of the 259 enrolled subjects, 235 completed part 1; 154 subjects (n = 77 each for RCI and placebo) entered part 2, and 127 (RCI, n = 71; placebo, n = 56) completed. At week 12, 163 subjects (62.9%) achieved LDA and 169 (65.3%) achieved CDAI ≤ 10 (both p \u3c 0.0001). At week 24, 47 (61.0%) RCI-treated and 32 (42.1%) placebo-treated subjects maintained LDA (p = 0.019); 66 (85.7%) RCI-treated and 50 (65.8%) placebo-treated subjects maintained CDAI ≤ 10 (p = 0.004). No unexpected safety signals were observed. CONCLUSIONS: RCI was effective and generally safe in patients with active RA despite corticosteroid/DMARD therapy. By week 12, \u3e 60% of patients achieved LDA, which was maintained with 12 additional weeks of treatment. Most patients who achieved LDA maintained it for 3 months after RCI discontinuation. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02919761

Process for preparing tapes from thermoplastic polymers and carbon fibers

The instant invention involves a process for use in preparing tapes or rovings, which are formed from a thermoplastic material used to impregnate longitudinally extended bundles of carbon fibers. The process involves the steps of (a) gas spreading a tow of carbon fibers; (b) feeding the spread tow into a crosshead die; (c) impregnating the tow in the die with a thermoplastic polymer; (d) withdrawing the impregnated tow from the die; and (e) gas cooling the impregnated tow with a jet of air. The crosshead die useful in the instant invention includes a horizontally extended, carbon fiber bundle inlet channel, means for providing melted polymer under pressure to the die, means for dividing the polymeric material flowing into the die into an upper flow channel and a lower flow channel disposed above and below the moving carbon fiber bundle, means for applying the thermoplastic material from both the upper and lower channels to the fiber bundle, and means for withdrawing the resulting tape from the die

Patient‐Reported Outcomes From a Two‐Year Head‐to‐Head Comparison of Subcutaneous Abatacept and Adalimumab for Rheumatoid Arthritis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/122413/1/acr22763_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/122413/2/acr22763.pd

An International, Web-Based, Prospective Cohort Study to Determine Whether the Use of ACE Inhibitors prior to the Onset of Scleroderma Renal Crisis Is Associated with Worse Outcomes—Methodology and Preliminary Results

Background. To describe the methodology of a study designed to determine whether systemic sclerosis (SSc) patients with incident scleroderma renal crisis (SRC) on angiotensin converting enzyme (ACE) inhibitors prior to the onset of SRC have worse outcomes. Methods. Prospective, international cohort study of SRC subjects identified through an ongoing web-based survey. Every second Friday afternoon, an e-mail was sent to 589 participating physicians to identify new cases of SRC. Death or dialysis at one year after the onset of SRC will be compared in patients exposed or not to ACE inhibitors prior to the onset of SRC. Results. Fifteen months after the start of the survey, we had identified 76 incident cases of SRC. Of these, 66 (87%) had a hypertensive SRC and 10 (13%) a normotensive SRC. Twenty-two percent (22%) of the patients were on an ACE inhibitor immediately prior to the onset of the SRC. To date, we have collected one-year follow-up data on approximately 1/3 of the cohort. Of these, over 50% have died or remain on dialysis at one year. Conclusion. An international, web-based cohort study design is a feasible method of recruiting a substantial number of patients to study an infrequent vascular manifestation of SSc

Clinical disease activity and acute phase reactant levels are discordant among patients with active rheumatoid arthritis: acute phase reactant levels contribute separately to predicting outcome at one year

INTRODUCTION: Clinical trials of new treatments for rheumatoid arthritis (RA) typically require subjects to have an elevated acute phase reactant (APR), in addition to tender and swollen joints. However, despite the elevation of individual components of the Clinical Disease Activity Index (CDAI) (tender and swollen joint counts and patient and physician global assessment), some patients with active RA may have normal erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP) levels and thus fail to meet entry criteria for clinical trials. We assessed the relationship between CDAI and APRs in the Consortium of Rheumatology Researchers of North America (CORRONA) registry by comparing baseline characteristics and one-year clinical outcomes of patients with active RA, grouped by baseline APR levels. METHODS: This was an observational study of 9,135 RA patients who had both ESR and CRP drawn and a visit at which CDAI was \u3e 2.8 (not in remission). RESULTS: Of 9,135 patients with active RA, 58% had neither elevated ESR nor CRP; only 16% had both elevated ESR and CRP and 26% had either ESR or CRP elevated. Among the 4,228 patients who had a one-year follow-up visit, both baseline and one-year follow-up modified Health Assessment Questionnaire (mHAQ) and CDAI scores were lowest for patients with active RA but with neither APR elevated; both mHAQ and CDAI scores increased sequentially with the increase in number of elevated APR levels at baseline. Each individual component of the CDAI followed the same trend, both at baseline and at one-year follow-up. The magnitude of improvement in both CDAI and mHAQ scores at one year was associated positively with the number of APRs elevated at baseline. CONCLUSIONS: In a large United States registry of RA patients, APR levels often do not correlate with disease activity as measured by joint counts and global assessments. These data strongly suggest that it is appropriate to obtain both ESR and CRP from RA patients at the initial visit. Requiring an elevation in APR levels as a criterion for inclusion of RA patients in studies of experimental agents may exclude some patients with active disease