Faculty Bibliography
Searched for:
in-biosketch:true
person:yazicy01
Total Results:
429
APREMILAST FOR THE TREATMENT OF BEHCET'S SYNDROME: ROUTINE CARE, REAL WORLD EXPERIENCE [Meeting Abstract]
ISI:000388065900166
ISSN: 1593-098x
CID: 2332222
PROMs (MDHAQ/RAPID3) and physician rheumetric measures
pp. 59-99
ISBN: 9783319328515
CID: 2567252
Reductions in disease activity in the AMPLE trial: clinical response by baseline disease duration
OBJECTIVES: To evaluate clinical response by baseline disease duration using 2-year data from the AMPLE trial. METHODS: Patients were randomised to subcutaneous abatacept 125 mg weekly or adalimumab 40 mg bi-weekly, with background methotrexate. As part of a post hoc analysis, the achievement of validated definitions of remission (Clinical Disease Activity Index (CDAI) 6 months). Disease Activity Score 28 (C-reactive protein) <2.6 or 6 months) across multiple clinical measures. CONCLUSIONS: Abatacept or adalimumab with background methotrexate were associated with similar onset and sustainability of response over 2 years. Patients treated early or later in the disease course achieved comparable clinical responses. TRIAL REGISTRATION NUMBER: NCT00929864, Post-results.
PMCID:4838764
PMID: 27110385
ISSN: 2056-5933
CID: 2091932
Ocular Involvement of Behcet's Syndrome: a Comprehensive Review
Behcet's syndrome (BS) is a vasculitis involving several organ systems including the eyes. Ocular involvement is one of the most disabling complications of BS, causing loss of vision that may progress to blindness if left untreated. The typical form of ocular involvement is a relapsing and remitting panuveitis and retinal vasculitis. Initial attacks may spontaneously improve and subsequently disappear in a few weeks but tend to recur if left untreated. Destructive and recurrent attacks, especially with posterior segment and retina involvement, may cause irreversible ocular structural changes and permanent damage in sensory retina, resulting in loss of vision. The risk of irreversible damage to ocular tissue which may result in loss of vision warrants early and intensive treatment especially in patients at high risk such as young men who tend to follow an aggressive disease course. The management strategy involves rapid suppression of inflammation during the attacks and prevention of recurrent attacks. Local and systemic measures including immunosuppressives, corticosteroids, and biologic agents are used for this purpose. Surgery may be required in selected cases. The prognosis of eye involvement has greatly improved over the last decades with the effective use of immunosuppressives.
PMID: 24828904
ISSN: 1559-0267
CID: 992432
A Randomized Trial Comparing Disease Activity Measures for the Assessment and Prediction of Response in Rheumatoid Arthritis Patients Initiating Certolizumab Pegol
OBJECTIVE: The aim of the Patient/Physician Reported Efficacy Determination In Clinical Practice Trial (PREDICT; ClinicalTrials identifier NCT01255761) was to compare the patient-reported Routine Assessment of Patient Index Data 3 (RAPID-3) instrument with the investigator-based Clinical Disease Activity Index (CDAI) for assessing certolizumab pegol (CZP) treatment response in rheumatoid arthritis patients at 12 weeks and to predict the treatment response at week 52 using the data from week 12 (coprimary end points). METHODS: Patients received 400 mg of CZP at weeks 0, 2, and 4 (loading dose), followed by 200 mg every 2 weeks thereafter. Patients were randomized 1:1 to assessment with the RAPID-3 or the CDAI. Responder classification was performed at week 12; treatment response was defined as a score of 22 or RAPID-3 score >12) at 2 consecutive visits were withdrawn from the study. RESULTS: Patients had longstanding disease (mean 8.9 years) and high levels of disease activity (mean scores of 6.3 on the DAS28-ESR, 16.1 on the RAPID-3, and 40.2 on the CDAI). Previous anti-tumor necrosis factor therapy had failed in 55.5% of them. At week 12, a total of 64.7% (by RAPID-3) and 76.4% (by CDAI) of the patients were classified as responders (difference of -11.9% [95% confidence interval -18.4%, -5.3%]). At week 52, a total of 31.5% (by RAPID-3) and 32.3% (by CDAI) of the responders achieved a low level of disease activity on the DAS28-ESR (difference of -1.3% [95% confidence interval -9.3%, 6.6%]). CONCLUSION: The CDAI classified more patients as CZP responders at week 12 than did the RAPID-3. Although these outcome measures were not statistically comparable, the positive predictive value for low disease activity at week 52 was similar. As these tools cover differing domains of therapy response, further evaluation for clinical disease activity assessments and treatment decisions is needed.
PMCID:5063165
PMID: 26316013
ISSN: 2326-5205
CID: 1882612
Pulmonary artery aneurysms in Behcet's syndrome: a review of the literature with emphasis on geographical differences
OBJECTIVES: To investigate the frequency of Behcet's syndrome (BS) with pulmonary artery aneurysms (PAA) publications, the most lethal complication of BS, as reported from different countries and to provide a review of diagnostic techniques, treatment approaches and prognosis. METHODS: Countries from each continent with a population of 4 million and over were chosen (n=128). A PubMed search for "BS, PAA and the country name" was conducted and 23 countries with BS and PAA were identified. The full texts of articles (n=91) were analysed for data including gender, age, accompanying vascular findings, diagnostic techniques, treatment modalities and mortality rates. RESULTS: A total of 207 (183 males, 24 females) patients with BS and PAA were reported in 91 articles originating from 23 countries. As expected there was a significant correlation (r=0.88, p<0.001) between the total number of articles about BS (n=4431) and those related to PAA and BS. In a simple linear regression analysis the number of BS and PAA articles from Japan was significantly below the identity line while in Turkey there was a propensity to publish more articles related to PAA than expected. One hundred and sixteen patients (56%) were treated with immunosuppressive therapy. Biologics were used only in 5 patients (2%). Of the 207 patients, 62 (30%) died. CONCLUSIONS: PAA is mostly reported as case reports from countries where BS is common. PAA might be uncommon in Japan. The prognosis of PAA could be getting better.
PMID: 26211653
ISSN: 0392-856x
CID: 1743882
A patient-reported outcome measures-based composite index (RAPID3) for the assessment of disease activity in ankylosing spondylitis
A single questionnaire regarding to disease activity for all rheumatic diseases may present advantages to introduce quantitative measurement into routine care. The aim of this study was to evaluate the correlation of routine assessment of patient index data 3 (RAPID3) with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS). A total of 341 consecutive AS patients who met the modified New York classification criteria were included. All patients completed BASDAI and RAPID3 at each visit, and their physicians completed physician global assessment. ASDASs were calculated using defined formulas. Proposed RAPID3 severity categories were compared to BASDAI and ASDAS categories. Spearman's rho correlation test and kappa statistics were used to analyze statistical significance. The median age of AS patients was 34.0 (21.0-69.0) years and the median disease duration 10.0 (2.0-35.0) years. Median scores for RAPID3, BASDAI, ASDAS-CRP, and ASDAS-ESR were 13.0 (0.0-27.3), 4.7 (0.0-9.7), 3.0 (0.4-5.8), and 2.5 (0.5-6.3), respectively. RAPID3 was strongly correlated with BASDAI and ASDAS-ESR (r = 0.842, r = 0.815; p < 0.001, respectively). Among the 209 patients with high disease activity according to BASDAI, 83.3 % had high or moderate severity according to RAPID3 (kappa 0.693; p < 0.001). Among the 133 patients with moderate, high, and very high disease activity on ASDAS-CRP, 91.7 % had high or moderate severity according to RAPID3 (kappa 0.548; p < 0.001). RAPID3 is as informative as BASDAI and ASDAS in our cohort of AS patients. We therefore suggest that RAPID3 may be used to assess the patient status quantitatively in AS patients, as part of routine care.
PMID: 25794571
ISSN: 0172-8172
CID: 1506582
Limitations of clinical trials in chronic diseases: is the efficacy of methotrexate (MTX) underestimated in polyarticular psoriatic arthritis on the basis of limitations of clinical trials more than on limitations of MTX, as was seen in rheumatoid arthritis?
Clinical trials are the optimal method to establish efficacy of a drug versus placebo or another drug. Nonetheless, important limitations are seen, particularly in chronic diseases over long periods, although most are ignored. Pragmatic limitations of clinical trials include a relatively short observation period, suboptimal dosage schedules, suboptimal surrogate markers for long-term outcomes, statistically significant results which may not be clinically unimportant and vice versa. Even ideal clinical trials have intrinsic limitations, including the influence of design on results, data reported in groups which ignore individual variation, non-standard observer-dependent interpretation of a balance of efficacy and toxicity, and distortion of a "placebo effect." Limitations are seen in many clinical trials of methotrexate (MTX) in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). The first MTX clinical trial in rheumatology documented excellent efficacy in PsA, but frequent adverse events in 1964, explained by intravenous doses up to 150 kg. MTX was abandoned until the 1980s for RA, while gold salts and penicillamine were termed "remission-inducing," on the basis limitations of clinical trials. In the most recent MTX in PsA (MIPA) trial, all outcomes favoured MTX, but only patient and physician global estimates met the p<0.05 criterion. A conclusion of "no evidence for MTX improving synovitis" appears explained by insufficient statistical power, wide individual variation, no subsets, low doses, and other limitations. MTX appears less efficacious in PsA than RA, but may be underestimated in PsA, similar to historical problems in RA, resulting more from limitations of clinical trials than from limitations of MTX.
PMID: 26472658
ISSN: 0392-856x
CID: 1859702
Improvement Thresholds for Morning Stiffness Duration in Patients Receiving Delayed- Versus Immediate-Release Prednisone for Rheumatoid Arthritis
BACKGROUND: Morning stiffness, a common patientreportedsymptom in rheumatoid arthritis, is associated withan increase in early morning inflammatory cytokines andsignificant disability. Little is known about categorical morningstiffness responses to glucocorticoid use in rheumatoidarthritis patients. Chronic pain threshold models have indicatedpreviously that response rates of 15% to 30% indicateminimally important relief, 40% to 50% indicate substantialpain relief, and greater than 70% represents extensive painrelief. The objective of the present analysis was to assessdifferences in the percentages of patients achieving 25%(minimally important change), 50% (substantial change),and 75% (extensive change) reduction in the duration ofpatient-reported morning stiffness between patients receivingDR- and IR-prednisone in the Circadian Administrationof Prednisone in Rheumatoid Arthritis (CAPRA-1) trial. MATERIALS AND METHODS: The CAPRA-1 trial was a12-week, double-blind study followed by an additional9-month open-label extension. Patients in the CAPRA-1trial were randomized to IR-prednisone in the morning orDR-prednisone at bedtime in addition to stable diseasemodifyingantirheumatic drug therapy. After the doubleblindphase, patients randomized to IR-prednisone (N =110) were switched to DR-prednisone and followed at 3, 6,and 9 months in an open-label extension phase. Patientsoriginally randomized to DR-prednisone (N = 97) continuedthat therapy in the open-label extension. Patient morningstiffness diary entries from 4 weeks before and 4 weeks aftereach scheduled visit were analyzed over 1 year for thresholdresponse. The number of patients reaching thresholdresponse (25%, 50%, and 75% improvement) and time tomorning stiffness response were examined. RESULTS: The DR-prednisone arm had significantly moreresponders in all three morning stiffness threshold responsecategories at the end of the double-blind period comparedwith IR-prednisone (p
PMID: 26535595
ISSN: 2328-5273
CID: 1927612
Impact of concomitant methotrexate dose on the efficacy and safety of sarilumab for treatment of moderate-to-severe rheumatoid arthritis: the mobility study [Meeting Abstract]
Background: Methotrexate (MTX) is the most commonly used conventional synthetic DMARD (csDMARD) for the treatment of rheumatoid arthritis (RA). In the phase 3 MOBILITY study (NCT01061736),1 of sarilumab in inadequate responders to MTX, MTX was continued at the dose prescribed at screening, which was assumed to be the maximally tolerated dose. This sub-analysis evaluates whether the different doses of MTX, in association with sarilumab, had an effect on efficacy or safety outcomes in MOBILITY. Objectives: To explore the relationship of MTX dose on the efficacy or safety of sarilumab in the treatment of active RA in MTX-IR patients. Methods: The MOBILITY study design and methods have been reported.2 Patients were required to be on a stable dose of MTX of 10-25 mg/wk for at least 6 weeks, except for Asian-Pacific region patients (6-25 mg/wk) prior to enrolment and to maintain this dose throughout the trial. A sufficient number of subjects with doses of 7.5-25 mg/wk were included: 11 (0.92%) patients were excluded from the analysis due to small numbers receiving doses of <7.5 and >25mg/wk. The relationship between efficacy and safety outcomes for sarilumab and MTX was assessed by appropriate regression models (logistic or generalized linear) in this post hoc analysis. Results: 1186 patients were included. For each dose group in each treatment arm we computed proportions of ACR20 responders at Wk 24 and 52; no apparent difference in achieving an ACR20 response was observed with increasing MTX dose in any treatment group (Figure). A logistic regression assessment confirms this observation: for sarilumab 150 mg and 200 mg. Based on mean change from baseline in HAQ-DI at Wk 24, no apparent relationship with MTX dose was observed. A linear regression model assessment provides confirmation of the results. There was no statistical difference in mean HAQ-DI change from baseline based on MTX dose in the Pbo, sarilumab 150 mg or sarilumab 200 mg groups. Similar findings were observed for changes from baseline for DAS28-CRP, FACIT-Fatigue, and mTSS (change and progression). There was no association of the incidence of treatment-emergent adverse events (AE), serious AEs and changes in ALT, neutrophil counts and lipids with increasing MTX doses. Conclusions: In this post hoc analysis, within the sarilumab 150 mg or sarilumab 200 mg dose groups, efficacy or safety was similar across concomitant MTX Doses. (Figure Presented)
EMBASE:72152359
ISSN: 0003-4967
CID: 1926182
