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Jeffrey R. Curtis - One of the best experts on this subject based on the ideXlab platform.

  • Risk of Hypersensitivity to Biologic Agents Among Medicare Patients With Rheumatoid Arthritis.
    Arthritis care & research, 2017
    Co-Authors: Huifeng Yun, Fenglong Xie, Kenneth G Saag, Lang Chen, James D Lewis, Randall N. Beyl, Jeffrey R. Curtis
    Abstract:

    Background Hypersensitivity reactions (HSRs) can occur with any of the available Biologic Agents used to treat rheumatoid arthritis (RA). We compared drug-specific risks for HSRs among RA patients enrolled in the US Medicare program. Methods Using Medicare data, we identified new users of infused infliximab, abatacept, rituximab, tocilizumab, golimumab, and injected Biologic Agents. After identifying HSRs using validated algorithms, for each Biologic Agent, we calculated the cumulative incidence over 6 months and the incidence rates (IRs) in 0–1, 2–14, and 15–30 days of administration. For each Biologic Agent administration, followup started on the infusion/injection date and ended at HSR, subsequent Biologic Agent administration, death, coverage loss, 30-day followup, or December 31, 2013, whichever occurred first. Adjusted robust Poisson regression was used to compare the HSR risks across Biologic Agents. A sensitivity analysis was conducted using a nested case-crossover design. Results We identified 725,591 Biologic Agent administrations and 248 HSRs among 80,587 new users of Biologic Agents. Of these, 26.9% occurred in users of intravenous abatacept, 4.6% in rituximab, 5.8% in intravenous tocilizumab, 22.9% in infliximab, and 39.7% in injectable anti–tumor necrosis factor inhibitors (anti-TNFi). The cumulative incidence of HSRs over 6 months for all Biologic Agents was low (

  • risk of hospitalized infection among rheumatoid arthritis patients concurrently treated with a Biologic Agent and denosumab
    Arthritis & Rheumatism, 2015
    Co-Authors: Jeffrey R. Curtis, Fenglong Xie, Huifeng Yun, Kenneth G Saag, Lang Chen, Elizabeth Delzell
    Abstract:

    Objective Denosumab is a Biologic Agent used to treat osteoporosis. Its safety profile given concurrently with Biologic drugs for rheumatoid arthritis (RA) has not been well studied. We evaluated hospitalized infections among patients treated with Biologic Agents for RA who initiated denosumab or zoledronic acid (ZA), a parenteral bisphosphonate without known associations with infection. We hypothesized that the rate of hospitalized infection with denosumab would be noninferior to ZA. Methods We identified RA patients enrolled in Medicare in 2006–2012 treated with Biologic Agents who initiated denosumab or ZA. Cox proportional hazards models compared the risk for hospitalized infection, comparing denosumab users to ZA users and adjusting for potentially confounding factors. A noninferiority margin was specified a priori to demonstrate that denosumab had no greater infection risk than ZA if the upper bound of the 95% confidence interval (95% CI) of the hazard ratio (HR) was <1.5. Results Eligible RA patients receiving Biologic Agents initiated denosumab (n = 1,354) or ZA (n = 4,460). Characteristics of the denosumab users were as follows: mean ± SD age 73.0 ± 8.9, 98.2% women, with a majority receiving infliximab (35.7%) or abatacept (18.6%). Denosumab users had a higher prevalence of prior infections (11.5% hospitalized and 48.3% outpatient) and infection-related risk factors. The crude rate of hospitalized infections for denosumab (14.9/100 person-years [95% CI 12.2–18.1]) was comparable to that for ZA (13.9/100 person-years [95% CI 12.5–15.4]). After adjustment, the HR of hospitalized infection for denosumab users was noninferior to that for ZA users (HR 0.89 [95% CI 0.69–1.15]). Conclusion The rate of hospitalized infection among RA patients receiving denosumab concurrently with Biologic Agents for RA was not increased compared to those receiving zoledronate.

  • risks of herpes zoster in patients with rheumatoid arthritis according to Biologic disease modifying therapy
    Arthritis Care and Research, 2015
    Co-Authors: Elizabeth Delzell, Kenneth G Saag, Lang Chen, Emily B Levitan, James D Lewis, Timothy Beukelman, Kevin L Winthrop, John W Baddley, Jeffrey R. Curtis
    Abstract:

    Objective To evaluate whether the risks of herpes zoster (HZ) differed by Biologic Agents with different mechanisms of action (MOAs) in older rheumatoid arthritis (RA) patients. Methods Using Medicare data from 2006–2011, among RA patients with prior Biologic Agent use and no history of cancer or other autoimmune diseases, this retrospective cohort study identified new treatment episodes of abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab, rituximab, and tocilizumab. Followup started on initiation of the new Biologic Agent and ended at any of the following: first incidence of HZ, a 30-day gap in current exposure, death, a diagnosis of other autoimmune disease or cancer, loss of insurance coverage, or December 31, 2011. We calculated the proportion of RA patients vaccinated for HZ in each calendar year prior to Biologic Agent initiation and HZ incidence rate for each Biologic Agent. We compared HZ risks among therapies using Cox regression adjusted for potential confounders. Results Of 29,129 new Biologic treatment episodes, 28.7% used abatacept, 15.9% adalimumab, 14.8% rituximab, 12.4% infliximab, 12.2% etanercept, 6.1% tocilizumab, 5.8% certolizumab, and 4.4% golimumab. The proportion of RA patients vaccinated for HZ prior to Biologic Agent initiation ranged from 0.4% in 2007 to 4.1% in 2011. We identified 423 HZ diagnoses with the highest HZ incidence rate for certolizumab (2.45 per 100 person-years) and the lowest for golimumab (1.61 per 100 person-years). Neither the crude incidence rate nor the adjusted hazard ratio differed significantly among Biologic Agents. Glucocorticoid use had a significant association with HZ. Conclusion Among older patients with RA, the HZ risk was similar across Biologic Agents, including those with different MOAs.

  • systematic review of tocilizumab for rheumatoid arthritis a new Biologic Agent targeting the interleukin 6 receptor
    Clinical Therapeutics, 2012
    Co-Authors: Iris Navarromillan, Jasvinder A Singh, Jeffrey R. Curtis
    Abstract:

    Abstract Background Tocilizumab (TCZ), a humanized anti–interleukin-6 receptor monoclonal antibody, represents a new treatment strategy for patients with rheumatoid arthritis (RA) and is currently approved in the United States for RA patients who have failed to improve with at least one anti–tumor necrosis factor therapy. Objective The goal of this study was to summarize the efficacy and safety profile of TCZ. Methods A systematic literature review was conducted to identify English-language articles within PubMed and the Cochrane Library from January 1989 to August 2011 reporting results from Phase III TCZ double-blind, randomized controlled trials (RCTs), noncontrolled clinical trials, and open-label extensions with a duration ≥6 months. Study outcomes had to include at least one of the following: American College of Rheumatology (ACR) 20, 50, or 70 response rates; tender/swollen joint count; Health Assessment Questionnaire–Disability Index; radiographic outcomes and drug persistence. Phase II RCTs were included only if they contained relevant information not available in Phase III RCTs. Relevant studies were selected to evaluate TCZ's pharmacokinetics and pharmacodynamics. Results Ten published clinical trials (7 Phase III, 3 Phase II) for TCZ were retrieved (7833 articles initially identified) from PubMed and 31 from the Cochrane library. Compared with methotrexate (MTX) monotherapy, TCZ 8 mg/kg IV monotherapy had higher rates of ACR20 ( P P = 0.002), and ACR70 ( P P P Conclusion The short-term efficacy and safety profile of TCZ is promising. Additional long-term safety data are needed to better characterize the risk–benefit profile of this Agent.

Naoki Ishiguro - One of the best experts on this subject based on the ideXlab platform.

  • ab0415 tendency to choose first Biologic Agent therapy of rheumatoid arthritis in the elderly results from japanese multicenter registry
    Annals of the Rheumatic Diseases, 2017
    Co-Authors: Tsuyoshi Watanabe, T Kojima, N Takahashi, Shuji Asai, Nobuyuki Asai, Takuya Matsumoto, Yasumori Sobue, Naoki Ishiguro
    Abstract:

    Background Of the treatment of rheumatoid arthritis (RA), Biologic Agent therapies are chosen, if disease activity remains moderate or high despite csDMARDs therapy. In the elderly, with comorbidity and their less spare ability, safety is often concerned in the choice of Biologic Agent. Objectives We investigated the tendency to choose Biologic Agent and drug continuation rates in elderly in last decade. Methods Records of relevant patients with RA were collected from the Tsurumai Biologic Communication Registry, wherein the department of Nagoya University and 20 affiliated hospitals in Japan are enrolled. A total of 873 Biologics-naive and age 65 and older patients were recruited from January 2004 to December 2014. We studied the choice of the Biologic Agent year by, and baseline disease activity and concomitant methotrexate (MTX) among TNF inhibiters, tocilizumab (TCZ), and abatacept (ABT) groups. Drug continuation rates were compared among TNF inhibiters, TCZ, and ABT groups. Results From 2005 to 2010, etanercept (ETN) was used the most (2007; 73.5%, 2009; 65.9%). After the advent of ABT, ABT was used the most (2011; 44.3%, 2014; 38.8%). Baseline disease activity slightly decreased as a whole (DAS28-CRP; 4.88 to 4.44). Despite baseline disease activity of TNF inhibitors group decreased (DAS28-CRP; 4.88 to 4.37), that of TCZ group increased (DAS28-CRP; 4.94 to 6.24). In 2011–2014, baseline disease activity of TCZ group (5.85) was higher than that of TNF inhibiters group (5.11) (p Conclusions ETN was used most before the advent of ABT. After the advent of ABT, ABT was used most and ETN decreased. This selection was made for speculation that ABT is lower risk than other Biological Agents. Baseline disease activity slightly decreased showing that tight control management became also popular among elderly. In 2011–2014, concomitant MTX rate and dose were lower in ABT group, but 2 years drug continuation rate was the highest. Disclosure of Interest None declared

  • sat0094 the association between methotrexate use and effects of treatment with a second Biologic Agent in rheumatoid arthritis
    Annals of the Rheumatic Diseases, 2016
    Co-Authors: Yoshikazu Ogawa, T Kojima, N Takahashi, K Funahashi, Naoki Ishiguro
    Abstract:

    Background In general, the concomitant use of methotrexate (MTX) and Biologic disease-modifying antirheumatic drugs (DMARDS) plays an important role in treatment for bio-naive patients with rheumatoid arthritis (RA). However, it remains unclear whether concomitant use of MTX is related to the effects of treatment with second Biologic DMARDS in RA patients for whom first Biologic DMARDS therapy have failed. Objectives The objective of the current study was to determine whether, and if so to what extent, concomitant use of MTX was associated with the effects of treatment with second Biologic DMARDS, especially in the context of whether or not tumor necrosis factor inhibitor (TNFi) had been used. Methods We used demographic and clinical data from the Tsurumai Biologics Communication Registry, which comprises Nagoya University and 20 affiliated hospitals in Japan. Patients aged 20–80 years who fulfilled the ACR 1987 revised classification criteria or the 2010 ACR/EULAR classification criteria for RA were selected; only those switching to second Biologic DMARDS therapy were included. Multivariate logistic regression analysis was used to assess the association between MTX use and the possibility of sufficient response to second Biologic DMARDS treatment, as defined by good response at week 16 in the EULAR response criteria, based on DAS28. Crude and adjusted odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were calculated. Adjustment variables included sex, age, disease duration, whether or not TNFi had been used in RA treatments with first and second Biologic DMARDS, use of MTX in first Biologic treatment, and use of glucocorticoids in treatment with second Biologic DMARDS. We determined the statistical significance of potential subgroup effect of whether or not TNFi had been used as second Biologics by testing the significance of the interaction terms added to our multivariable models. Results The demographic and disease characteristics of the patients at baseline were comparable except for the proportion of TNFi between patients not using MTX (n=49) and those treated concomitantly with MTX (n=122). The mean age was 59 years; 86% were women. Patients had longstanding RA (mean 10.6 years), and the baseline DAS28 was 5.2. Among the patients, 68% received glucocorticoids. The mean dose of MTX was 8.0 mg/week in patients using MTX. The proportion of TNFi was 26.5% in patients not using MTX and 62.3% in those using MTX, respectively. A good response as per EULAR response criteria was identified in 14 (28.6%) patients not using MTX and 58 (47.5%) patients treated concomitantly with MTX. The crude OR for the association between concomitant use of MTX and the possibility of good response as per EULAR response criteria was 2.27 (95% CI 1.11–4.63) compared with nonuse of MTX. After adjustment for the aforementioned covariates, concomitant use of MTX was associated with an increased possibility of good response to Biologic DMARDS compared with nonuse of MTX (OR 2.77, 95% CI 1.04–7.36). This multivariable adjusted effect estimate was not modified by whether or not TNFi had been used (P value for interaction greater than 0.05). Conclusions This study demonstrated that concomitant use of MTX was independently associated with an increased possibility of good response to second Biologic DMARDS regardless of whether or not TNFi had been used in RA treatment. Disclosure of Interest None declared

  • ab0255 the association between rheumatoid factor positivity and effects of treatment with a first Biologic Agent in rheumatoid arthritis
    Annals of the Rheumatic Diseases, 2016
    Co-Authors: Yoshikazu Ogawa, T Kojima, N Takahashi, K Funahashi, Naoki Ishiguro
    Abstract:

    Background The presence of rheumatoid factor (RF) plays an important role in diagnosis for patients suspected with rheumatoid arthritis (RA) [1]. However, it remains unclear whether RF positivity is related to the effects of treatment with Biologic disease-modifying antirheumatic drugs (DMARDS). Objectives The objective of the current study was to determine whether RF positivity was associated with the effects of treatment with Biologic DMARDS among bio-naive RA patients. Methods We used demographic and clinical data from the Tsurumai Biologics Communication Registry, which comprises Nagoya University and 20 affiliated hospitals in Japan. Patients aged 20–80 years who fulfilled the ACR 1987 revised classification criteria or the 2010 ACR/EULAR classification criteria for RA were selected; those with prior exposure to Biologic DMARDS were excluded. The RF status was divided into negative (0–15 IU/ml) or positive (>15 IU/ml). Multivariate logistic regression analysis was used to assess the association between RF positivity and the possibility of sufficient response to Biologic DMARDS treatment, as defined by good response at week 16 in the EULAR response criteria, based on DAS28. Crude and adjusted odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were calculated. Adjustment variables included sex, age, whether or not tumor necrosis factor inhibitor had been used, baseline use of methotrexate (MTX) and glucocorticoids, and baseline stage and class as defined by the Steinbrocker classification. Results The demographic and disease characteristics of the patients at baseline were comparable between RF-negative (n=120) and RF-positive (n=557) groups. The mean age was 57 years; 81% were women. Patients had longstanding RA (mean 9.3 years), and the baseline DAS28 was 5.1. Among the patients, 80% and 61% received MTX and glucocorticoids, respectively. A good response as per EULAR response criteria was identified in 73 (60.8%) RF-negative patients and 268 (48.1%) RF-positive patients. The crude OR for the association between RF positivity and the possibility of good response as per EULAR response criteria was 0.60 (95% CI 0.40–0.89) compared with RF negativity. After adjustment for the aforementioned covariates, RF-positivity was associated with a decreased possibility of good response to Biologic DMARDS compared with RF-negativity (OR 0.64, 95% CI 0.41–0.98). Conclusions This study demonstrated that RF-positivity was independently associated with a decreased possibility of good response to Biologic DMARDS in bio-naive RA patients. References P.Y. Chang, C.T. Yang, C.H. Cheng, K.H. Yu, Diagnostic performance of anti-cyclic citrullinated peptide and rheumatoid factor in patients with rheumatoid arthritis, Int J Rheum Dis, (2015). Disclosure of Interest None declared

A Martinez - One of the best experts on this subject based on the ideXlab platform.

  • fri0186 influence of immunogenicity to the first tnf i therapy on response to the second Biologic Agent in ra patients
    Annals of the Rheumatic Diseases, 2017
    Co-Authors: P Bogas, C Plasencia, Dora Pascualsalcedo, G Bonilla, E Moral, C Tornero, L Nuno, A Villalba, D Peiteado, A Martinez
    Abstract:

    Background There is currently no consensus on selecting a therapeutic target in patients (pts) non-responsive to their first TNF-inhibitors (TNF-i). The development of anti-drug antibodies (ADA) is a frequent cause of secondary inefficacy in our pts with TNF-i and there is evidence that those who develop ADA at their 1st TNF-i achieve a higher degree of response to the second one, compared to ADA- pts. Thus ADA measurement can help in choosing a therapeutic target in pts who failed to respond to their 1st TNF-i Objectives To assess if development of ADA to the 1st TNF-i determines better response when switching to a 2nd TNF-i versus a nonTNF-i. As secondary objective, analyze whether the presence or absence of ADA to a 1st TNF-i influences the efficacy of a 2nd TNF-i Methods Of a total of 144 pts that switched from infliximab or Adalimumab to a 2nd Biologic Agent (Etanercept, Rituximab, Tocilizumab, Adalimumab, Abatacept, Certolizumab and Infliximab), only 60, who had measured drug levels (DL)/ADA at discontinuation of the 1st TNF-I, were included. Clinical response was evaluated with DAS28, Delta-DAS28 (ΔDAS28) and EULAR response (E-resp) at 6 (v-6) and 12 (v-12) months after initiating 2nd Biologic Agent and at the last visit prior to drug discontinuation or ending of the study for those who did not interrupt the Biological therapy (v-end). DL/ADA levels were measured by ELISA. Statistical analysis was performed using SPSS version 20.0 Results Within the 60 pts who had measured DL/ADA at suspension of the 1st TNF-i, 26 (43%) were ADA- (i.e. DL +). In this ADA- subpopulation, 50% changed to a 2nd TNF-i; at v-6 there were no differences between switchers to a 2nd TNF-i and switchers to a nonTNF-i in DAS28 (3.7±2.1 TNF-i vs 4.2±1.1 nonTNF-i, p=0.286), ΔDAS28 (1,4±2 TNF-i, 1±1,2 nonTNF-i, p=0,374) and resp-E (75% good/moderate resp in TNF-I, 40% in nonTNF-i, p=0,064). At v-12, switchers to a 2nd TNF-i showed a lower DAS28 (2.5±0.6 TNF-i, 3.9±0.9 nonTNF-i, p=0.009) and a higher good E-resp rate with a marginally significant difference (80% in TNF-i, 22% in nonTNF-i, p=0.071). However, at v-end, pts with a 2nd nonTNF-i had better response (DAS28 >5,1 in 50% of TNF-i pts, 0% of nonTNF-i, p=0.044). Likewise ΔDAS28 at v-end was higher in the nonTNF-i group with trend to significance (0,7±1,7 TNF-i, 1,7±0,8 nonTNF-i, p=0,06). Along these lines, the good/moderate E-resp rate was higher in switchers to a nonTNF-i (70% in TNF-i, 8.3% in nonTNF-i, p=0.006). In ADA+ subpopulation (n=34), no differences were found in clinical response at v-end in DAS28 (3.7±1.2 TNF-i, 3.9±1.1 non-TNF-i, p=0.64), ΔDAS28 (0,63±1,6 in TNF-i, 1,4±1,4 in nonTNF-i, p=0,35) and good/moderate E-resp rate (30% in TNF-i, 91% in nonTNF-i, p=0,703). In pts who changed to a 2nd TNF-i, those with ADA to 1st TNF-i had a higher good response rate than ADA- pts (65% in ADA +, 30% in ADA-, p=0.07) Conclusions The development of ADA to the first TNF-i entails a better response when switching to a 2nd TNF-i, with a similar efficacy to the pts who switched to a nonTNF-i. In those pts who did not develop immunogenicity to the 1st TNF-I, there is a better response when changing therapeutic target. The ADA measurement can help to select the pts who can benefit from a 2nd TNF-i Disclosure of Interest None declared

  • fri0204 comparison the long term clinical outcomes between nontnf inhibitors versus tnf i in ra patients who failed to a first tnf i
    Annals of the Rheumatic Diseases, 2017
    Co-Authors: P Bogas, C Plasencia, Dora Pascualsalcedo, G Bonilla, E Moral, C Tornero, L Nuno, A Villalba, D Peiteado, A Martinez
    Abstract:

    Background There are many Biological therapies for Rheumatoid Arthritis (RA) with different mechanisms of action and good efficacy rate; however, up to 40% of patients (pts) fail to respond to the 1st Biologic Agent, and it is still not clear what strategy to follow after showing inadequate response to tumor necrosis factor α inhibitors (TNF-i) Objectives To assess the clinical response and survival (SVV), in our cohort of RA pts that discontinued the 1st TNF-i, of a 2nd TNF-i vs a nonTNF-i, both in the global cohort and in the subpopulation that dropped out the 1st TNF-I due to inefficacy Methods This observational study included 110 pts in the RA-Paz cohort who previously suspended Ifx (68%) or Ada (32%) between 1999–2016. Two groups were established as they switched to a TNF-i or nonTNF-i. Clinical response was evaluated by DAS28, Delta-DAS28 (ΔDAS28) and EULAR response (E-resp). The assessments were performed at 6 (v-6) and 12 months (v-12) since initiating 2nd Biological Agent and during the last visit prior to drug discontinuation or ending of the study for those who did not interrupt the drug (v-end). Statistical analysis was performed using SPSS version 20.0 Results Of the 110 pts who had stopped Ifx or Ada as 1st TNF-i, 65% changed to a 2nd TNF-i. The 84% of the overall pts were women. The mean age was 64±14 years and the mean time of 2nd Biologic drug was 3.71±3.51 years. 61% associated methotrexate at the beginning of 2nd Biologic Agent and 56% at the v-end, without differences between those who switched to TNF-i and those who did to nonTNF-i. At v-6 and v-12, there was no difference in ΔDAS28 [at v-6:1.3±1.4 in TNF-i and 1.2±1.2 in nonTNF-i (p=0.919), at v-12: 1.3±1.5 in TNF-I and 1.2±1.1 in nonTNF-i (p=0.852)]. In contrast, at v-end, pts with nonTNF-i showed a higher clinical improvement (ΔDAS28: 0.68±1.7 in TNF-i, 1.8±1.1 in nonTNF-i, p=0.002). At v-6, the TNF-i group achieved higher good E-resp rate (41% vs 18%, p=0.035), but there was no difference at v-12 (36% in TNF-I vs 23% in nonTNF-i, p=0.435). However, at v-end, the nonTNF-I group achieved better E-resp (good resp: 38% in nonTNF-i vs 25% in TNF-I, no resp 18% in nonTNF-i vs 50% in TNF-i, p=0.01). Likewise, 100% (n=7) of the pts that finished 2nd Biologic Agent by remission, had changed to a nonTNF-i (p Conclusions In our sample of RA patients who suspended Ifx/Ada as 1st TNF-i, switching to a 2nd Biologic Agent did not show relevant clinical differences between a TNF-i and a nonTNF-i within the 1st year of treatment. However, in the long-term, switching to a nonTNF-i shows enhanced clinical benefits with no impact on survival vis-a-vis a 2nd TNF-i. Despite the efficacy of TNF-i, new therapeutic targets are needed for those who fail to respond to these Biological Agents Disclosure of Interest None declared

Matthias H. Thomas - One of the best experts on this subject based on the ideXlab platform.

  • Golimumab as the First-, Second-, or at Least Third-Line Biologic Agent in Patients with Rheumatoid Arthritis, Psoriatic Arthritis, or Ankylosing Spondylitis: Post Hoc Analysis of a Noninterventional Study in Germany
    Rheumatology and Therapy, 2020
    Co-Authors: Klaus Krüger, Gerd Rüdiger Burmester, Siegfried Wassenberg, Matthias H. Thomas
    Abstract:

    Introduction While golimumab (GLM) has demonstrated efficacy in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) in several randomized clinical trials with Biologic-naïve patients, observational data from Biologic-experienced patients are sparse. We aimed to assess the effectiveness of GLM used as the first-, second-, or at least third-line Biologic Agent in RA, PsA, and AS patients in a real-world setting. Methods Post hoc analysis of the noninterventional, prospective, 24-month GO-NICE study of RA, PsA, and AS patients who initiated GLM 50 mg subcutaneously once monthly in a real-world setting in Germany. Results In 1454 patients with RA, PsA, or AS, GLM was administered as the first-line ( n  = 305, 286, 292, respectively), second-line ( n  = 104, 136, 130, respectively), or at least third-line ( n  = 64, 79, 58, respectively) Biologic Agent. In RA patients ( n  = 473), the time since first diagnosis was 9.7, 10.1, and 14.3 years, respectively. The DAS28 score at BL was 5.0, 4.9, and 5.1 in patients using GLM as a first-, second-, and third-line Biologic Agent, respectively, and dropped significantly in all groups. After 3 months of treatment, 27.5%, 19.5%, and 14.5% of patients were in remission; the corresponding values after 24 months were 45.3%, 50.0%, and 33.3%, respectively. In PsA patients ( n  = 501), time since fist diagnosis was 12.4, 13.7, and 13.8 years, respectively. Based on PsARC, a response was achieved at 24 months in the first-, second-, and third-line use of GLM in 76.4%, 51.0%, and 50.0% of the patients. In AS patients ( n  = 480), the time since first diagnosis was 9.4, 9.8, and 12.4 years in patients using GLM as the first-, second-, and at least third-line Biologic Agent, respectively. After 24 months of treatment, the mean BASDAI scores decreased significantly ( p  

  • golimumab as the first second or at least third line Biologic Agent in patients with rheumatoid arthritis psoriatic arthritis or ankylosing spondylitis post hoc analysis of a noninterventional study in germany
    Rheumatology and Therapy, 2020
    Co-Authors: Klaus Krüger, Gerd Rüdiger Burmester, Siegfried Wassenberg, Matthias H. Thomas
    Abstract:

    While golimumab (GLM) has demonstrated efficacy in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) in several randomized clinical trials with Biologic-naive patients, observational data from Biologic-experienced patients are sparse. We aimed to assess the effectiveness of GLM used as the first-, second-, or at least third-line Biologic Agent in RA, PsA, and AS patients in a real-world setting. Post hoc analysis of the noninterventional, prospective, 24-month GO-NICE study of RA, PsA, and AS patients who initiated GLM 50 mg subcutaneously once monthly in a real-world setting in Germany. In 1454 patients with RA, PsA, or AS, GLM was administered as the first-line (n = 305, 286, 292, respectively), second-line (n = 104, 136, 130, respectively), or at least third-line (n = 64, 79, 58, respectively) Biologic Agent. In RA patients (n = 473), the time since first diagnosis was 9.7, 10.1, and 14.3 years, respectively. The DAS28 score at BL was 5.0, 4.9, and 5.1 in patients using GLM as a first-, second-, and third-line Biologic Agent, respectively, and dropped significantly in all groups. After 3 months of treatment, 27.5%, 19.5%, and 14.5% of patients were in remission; the corresponding values after 24 months were 45.3%, 50.0%, and 33.3%, respectively. In PsA patients (n = 501), time since fist diagnosis was 12.4, 13.7, and 13.8 years, respectively. Based on PsARC, a response was achieved at 24 months in the first-, second-, and third-line use of GLM in 76.4%, 51.0%, and 50.0% of the patients. In AS patients (n = 480), the time since first diagnosis was 9.4, 9.8, and 12.4 years in patients using GLM as the first-, second-, and at least third-line Biologic Agent, respectively. After 24 months of treatment, the mean BASDAI scores decreased significantly (p < 0.001 vs. BL) to 2.1, 2.9, and 2.9 in the patients using GLM as the first-, second-, and at least third-line treatment, respectively. Golimumab is an effective treatment in patients with RA, PsA, and AS, irrespective of any pretreatment with Biologic Agents. ClinicalTrials.gov NCT01313858.

  • sat0166 golimumab as first second or at least third Biologic Agent in patients with rheumatoid arthritis ra psoriatic arthritis psa or ankylosing spondylitis as post hoc analysis of a non interventional study in germany
    Annals of the Rheumatic Diseases, 2019
    Co-Authors: Klaus Krueger, Siegfried Wassenberg, Gerd R Burmester, Astrid Thiele, Matthias H. Thomas
    Abstract:

    Background Golimumab (GLM) has demonstrated efficacy in RA, PsA, and AS in several randomized clinical trials with Biologic-naive patients. Data from real world practice comparing Biologic naive and experienced patients are lacking. Objectives The aim of this post hoc analysis is to assess effectiveness of GLM used as first, second, or at least third Biologic Agent in RA, PsA and AS in a real-life setting. Methods Post hoc analysis of the non-interventional, prospective, 24-month GO-NICE study with RA, PsA and AS patients (pts.) starting GLM 50mg SC once monthly in a real practice setting in Germany, details were shown earlier (1,2). Endpoint measures DAS28-ESR, PsARC, and BASDAI are shown as observed. Results In 1458 pts. with RA, PsA or AS GLM was administered as first (n=305, 286, 292, resp.), second (n=104, 136, 130 resp.), or at least third Biologic Agent (n=64, 79, 58 resp.). Biologic argents in previous treatments included Adalimumab (348), Etanercept (287), Infliximab (139), Tocilizumab (27), Rituximab (15), Certolizumab (14), or Abatacept (n=12). 43.0, 30.8, 39.1% of pts. with RA, 53.1, 38.2, 34.2% with PsA, and 53.8, 49.2, 41.4% with AS completed the study until month 24. RA pts (n=473) RF was positive in 76.9%, 70.2%, and 59.4%, ACPA + in 76.2%, 78.4%, 59.0%, and disease duration was 9.7, 10.1, 14.3 years, in pts. with GLM use as 1st, 2nd, at least 3rd line respectively. DAS28 score at BL was 5.0, 4.9, 5.1 in first, second, and at least third line use of GLM, respectively and dropped significantly in all groups (table). After 3 months of treatment 27.5%, 19.5%, 14.5% of pts. were in remission ( PsA pts (n=501) Disease duration was 12.4, 13.7, 13.8 yrs, in pts. with GLM use as 1st, 2nd, at least 3rd line respectively. PsARC response was achieved in 76.4%, 51.0% and 50.0% in first, second, and at least third line use of GLM, respectively at 24 months. AS pts (n=483) HLAB27-positive in 81.2%, 80.8%, and 74.1%, in pts. with GLM use as 1st, 2nd, at least 3rd line respectively. At BL 162 pts. had extra articular manifestations, most commonly iritis, enthesitis, IBD, and dactylitis (in 31.2%, 35.9%, and 43%, pts. respectively. Pts. with at least 2 previous bDMARDs had higher BASDAI at BL than pts. with GLM use in 1st or 2nd line: 5.7 vs. 5.0, and 4.9. After 24 months of treatment the mean BASDAI scores decreased significantly (p Overall safety findings were comparable to those reported in controlled trials and no new safety signals were detected. Conclusion In this non-interventional study of pts. with RA, PsA and AS, golimumab therapy was effective, with better outcomes achieved in Biologic-naive pts. Significant improvement of DAS and BASDAI was also achieved with GLM use in second line. Third line use of GLM results in less benefit. References [1] K. Kruger, et al. BMJ Open2018 [2] K. Kruger, et al. Rheumatology International39 (1) 2019 Disclosure of Interests Klaus Krueger: None declared, Gerd Rudiger Burmester Consultant for: Roche, Sanofi-Genzyme, Speakers bureau: Roche, Sanofi-Genzyme, Siegfried Wassenberg Grant/research support from: Roche Pharma, Consultant for: Abbvie, BMS, Chugai, Roche, Novartis, Pfizer, MSD, Speakers bureau: Abbvie, BMS, Pfizer, Janssen, Chugai, Celgene, Roche, Novartis, MSD, Astrid Thiele Consultant for: Biogen, Celgene, Chugai, Hexal, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, Matthias Thomas Employee of: MSD Sharp & Dohme GmbH Germany

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  • sat0094 the association between methotrexate use and effects of treatment with a second Biologic Agent in rheumatoid arthritis
    Annals of the Rheumatic Diseases, 2016
    Co-Authors: Yoshikazu Ogawa, T Kojima, N Takahashi, K Funahashi, Naoki Ishiguro
    Abstract:

    Background In general, the concomitant use of methotrexate (MTX) and Biologic disease-modifying antirheumatic drugs (DMARDS) plays an important role in treatment for bio-naive patients with rheumatoid arthritis (RA). However, it remains unclear whether concomitant use of MTX is related to the effects of treatment with second Biologic DMARDS in RA patients for whom first Biologic DMARDS therapy have failed. Objectives The objective of the current study was to determine whether, and if so to what extent, concomitant use of MTX was associated with the effects of treatment with second Biologic DMARDS, especially in the context of whether or not tumor necrosis factor inhibitor (TNFi) had been used. Methods We used demographic and clinical data from the Tsurumai Biologics Communication Registry, which comprises Nagoya University and 20 affiliated hospitals in Japan. Patients aged 20–80 years who fulfilled the ACR 1987 revised classification criteria or the 2010 ACR/EULAR classification criteria for RA were selected; only those switching to second Biologic DMARDS therapy were included. Multivariate logistic regression analysis was used to assess the association between MTX use and the possibility of sufficient response to second Biologic DMARDS treatment, as defined by good response at week 16 in the EULAR response criteria, based on DAS28. Crude and adjusted odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were calculated. Adjustment variables included sex, age, disease duration, whether or not TNFi had been used in RA treatments with first and second Biologic DMARDS, use of MTX in first Biologic treatment, and use of glucocorticoids in treatment with second Biologic DMARDS. We determined the statistical significance of potential subgroup effect of whether or not TNFi had been used as second Biologics by testing the significance of the interaction terms added to our multivariable models. Results The demographic and disease characteristics of the patients at baseline were comparable except for the proportion of TNFi between patients not using MTX (n=49) and those treated concomitantly with MTX (n=122). The mean age was 59 years; 86% were women. Patients had longstanding RA (mean 10.6 years), and the baseline DAS28 was 5.2. Among the patients, 68% received glucocorticoids. The mean dose of MTX was 8.0 mg/week in patients using MTX. The proportion of TNFi was 26.5% in patients not using MTX and 62.3% in those using MTX, respectively. A good response as per EULAR response criteria was identified in 14 (28.6%) patients not using MTX and 58 (47.5%) patients treated concomitantly with MTX. The crude OR for the association between concomitant use of MTX and the possibility of good response as per EULAR response criteria was 2.27 (95% CI 1.11–4.63) compared with nonuse of MTX. After adjustment for the aforementioned covariates, concomitant use of MTX was associated with an increased possibility of good response to Biologic DMARDS compared with nonuse of MTX (OR 2.77, 95% CI 1.04–7.36). This multivariable adjusted effect estimate was not modified by whether or not TNFi had been used (P value for interaction greater than 0.05). Conclusions This study demonstrated that concomitant use of MTX was independently associated with an increased possibility of good response to second Biologic DMARDS regardless of whether or not TNFi had been used in RA treatment. Disclosure of Interest None declared

  • ab0255 the association between rheumatoid factor positivity and effects of treatment with a first Biologic Agent in rheumatoid arthritis
    Annals of the Rheumatic Diseases, 2016
    Co-Authors: Yoshikazu Ogawa, T Kojima, N Takahashi, K Funahashi, Naoki Ishiguro
    Abstract:

    Background The presence of rheumatoid factor (RF) plays an important role in diagnosis for patients suspected with rheumatoid arthritis (RA) [1]. However, it remains unclear whether RF positivity is related to the effects of treatment with Biologic disease-modifying antirheumatic drugs (DMARDS). Objectives The objective of the current study was to determine whether RF positivity was associated with the effects of treatment with Biologic DMARDS among bio-naive RA patients. Methods We used demographic and clinical data from the Tsurumai Biologics Communication Registry, which comprises Nagoya University and 20 affiliated hospitals in Japan. Patients aged 20–80 years who fulfilled the ACR 1987 revised classification criteria or the 2010 ACR/EULAR classification criteria for RA were selected; those with prior exposure to Biologic DMARDS were excluded. The RF status was divided into negative (0–15 IU/ml) or positive (>15 IU/ml). Multivariate logistic regression analysis was used to assess the association between RF positivity and the possibility of sufficient response to Biologic DMARDS treatment, as defined by good response at week 16 in the EULAR response criteria, based on DAS28. Crude and adjusted odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were calculated. Adjustment variables included sex, age, whether or not tumor necrosis factor inhibitor had been used, baseline use of methotrexate (MTX) and glucocorticoids, and baseline stage and class as defined by the Steinbrocker classification. Results The demographic and disease characteristics of the patients at baseline were comparable between RF-negative (n=120) and RF-positive (n=557) groups. The mean age was 57 years; 81% were women. Patients had longstanding RA (mean 9.3 years), and the baseline DAS28 was 5.1. Among the patients, 80% and 61% received MTX and glucocorticoids, respectively. A good response as per EULAR response criteria was identified in 73 (60.8%) RF-negative patients and 268 (48.1%) RF-positive patients. The crude OR for the association between RF positivity and the possibility of good response as per EULAR response criteria was 0.60 (95% CI 0.40–0.89) compared with RF negativity. After adjustment for the aforementioned covariates, RF-positivity was associated with a decreased possibility of good response to Biologic DMARDS compared with RF-negativity (OR 0.64, 95% CI 0.41–0.98). Conclusions This study demonstrated that RF-positivity was independently associated with a decreased possibility of good response to Biologic DMARDS in bio-naive RA patients. References P.Y. Chang, C.T. Yang, C.H. Cheng, K.H. Yu, Diagnostic performance of anti-cyclic citrullinated peptide and rheumatoid factor in patients with rheumatoid arthritis, Int J Rheum Dis, (2015). Disclosure of Interest None declared