Because of the chronic nature of giant cell arteritis (GCA) and/or polymyalgia rheumatica (PMR), patients may require continued glucocorticoid treatment to achieve treatment targets or prevent disease relapse, resulting in high cumulative doses. This study evaluated patterns of glucocorticoid use and outcomes in patients with GCA, PMR, or both. This retrospective study used electronic medical records from a US rheumatology clinic utilizing the JointMan® (Discus Analytics, LLC) rheumatology software. Patients aged ≥ 50 years with a diagnosis of GCA or PMR and ≥ 1 entry for a glucocorticoid prescription after diagnosis were included. Outcomes at 2 years after glucocorticoid initiation included the proportion of patients discontinuing glucocorticoids for ≥ 6 months, proportion of patients discontinuing glucocorticoids for ≥ 6 months and remaining off glucocorticoids at 2 years, time to discontinuation of glucocorticoids for ≥ 6 months, and prednisone dose and were compared between patients with GCA only, PMR only, or GCA and PMR. At 2 years after the initiation of glucocorticoids, 32% of patients (26/91) with GCA, 32% (248/779) with PMR, and 27% (26/97) with GCA and PMR discontinued glucocorticoids for ≥ 6 months; 17, 23, and 18% discontinued glucocorticoids for ≥ 6 months and remained off glucocorticoids at 2 years, respectively. Median (range) time to discontinuation of glucocorticoids for ≥ 6 months was 202.5 (0–635) days and shorter in patients with both GCA and PMR vs. GCA or PMR only. The majority of patients required daily prednisone at 2 years, with similar doses observed between groups. Fewer than one-third of patients with GCA and/or PMR discontinued glucocorticoids for ≥ 6 months; the majority of patients required prednisone therapy for ≥ 2 years after its initiation. These data highlight the need for the use of more efficacious and glucocorticoid-sparing therapies in patients with GCA and/or PMR.

ObjectiveTo assess the safety, tolerability, pharmacokinetics, and efficacy of rituximab (RTX) in pediatric patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA).MethodsThe Pediatric Polyangiitis Rituximab Study was a phase IIa, international, open‐label, single‐arm study. During the initial 6‐month remission‐induction phase, patients received intravenous infusions of RTX (375 mg/m2 body surface area) and glucocorticoids once per week for 4 weeks. During the follow‐up period, patients could receive further treatment, including RTX, for GPA or MPA. The safety, pharmacokinetics, pharmacodynamics, and exploratory efficacy outcomes with RTX were evaluated.ResultsTwenty‐five pediatric patients with new‐onset or relapsing disease were enrolled at 11 centers (19 with GPA [76%] and 6 with MPA [24%]). The median age was 14 years (range 6–17 years). All patients completed the remission‐induction phase. During the overall study period (≤4.5 years), patients received between 4 and 28 infusions of RTX. All patients experienced ≥1 adverse event (AE), mostly grade 1 or grade 2 primarily infusion‐related reactions. Seven patients experienced 10 serious AEs, and 17 patients experienced 31 infection‐related AEs. No deaths were reported. RTX clearance correlated with body surface area. The body surface area–adjusted RTX dosing regimen resulted in similar exposure in both pediatric and adult patients with GPA or MPA. Remission, according to the Pediatric Vasculitis Activity Score, was achieved in 56%, 92%, and 100% of patients by months 6, 12, and 18, respectively.ConclusionIn pediatric patients with GPA or MPA, RTX is well tolerated and effective, with an overall safety profile comparable to that observed in adult patients with GPA or MPA who receive treatment with RTX. RTX is associated with a positive risk/benefit profile in pediatric patients with active GPA or MPA.

Background: The efficacy and safety of intravenous (IV) and subcutaneous (SC) tocilizumab (TCZ) in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and as monotherapy in patients with rheumatoid arthritis (RA) has been demonstrated in large clinical trials and real-world data studies. The Health Assessment Questionnaire Disability Index (HAQ-DI) is commonly used to assess physical function in patients with RA. While HAQ-DI outcomes at Week 24 in TCZ clinical trials have been reported, outcomes at Week 12 and results stratified by treatment response categories at Weeks 12 and 24 have not been previously described. Objectives: To report the association between change in HAQ-DI from baseline to Weeks 12 and 24 and Disease Activity Score in 28 joints (DAS28) response categories in patients who received TCZ or comparators in TCZ clinical trials. Methods: Data from patients with active RA who received TCZ or a comparator from 6 Phase III or IV TCZ-IV studies (OPTION [ NCT00106548 ], RADIATE [ NCT00106522 ], TOWARD [ NCT00106574 ] LITHE [ NCT00109408 ], ACT-RAY [ NCT00810199 ] and ADACTA [ NCT01119859 ]) and 1 Phase III TCZ-SC study (BREVACTA [ NCT01232569 ]) were analyzed. Mean change in HAQ-DI score at Weeks 12 and 24 was assessed in patients stratified by DAS28 disease activity level (DAS28 < 2.6 [remission], DAS28 ≥ 2.6 to ≤ 3.2 [low disease activity; LDA], DAS28 > 3.2 to ≤ 5.1 [moderate disease activity; MDA], DAS28 > 5.1 [high disease activity; HDA] at Weeks 12 and 24. The adjusted least squares mean (LSM) change from baseline was estimated using a mixed model with repeated measures, including region (North America vs non-North America), RA duration (> 2 years vs ≤ 2 years), baseline HAQ-DI and DAS28, treatment, visit, visit by treatment and visit by baseline HAQ-DI. Results: Data from 5051 patients were included. Across all studies, the mean duration of RA ranged from 6.3 to 12.6 years. At baseline, patients had severe RA with a mean DAS28 ≥ 6.3; baseline HAQ-DI was ≥ 1.5. At Week 12, patients who achieved remission or LDA had greater improvements in HAQ-DI than those in MDA or HDA (Figure 1). Results were similar at Week 24 (Figure 2). Among patients who received TCZ and achieved remission or LDA, mean improvement in HAQ-DI was ≥ 0.65 and ≥ 0.44, respectively, at Week 12 (Figure 1) and ≥ 0.48 and ≥ 0.43 at Week 24 (Figure 2). Mean changes in HAQ-DI were similar between patients who received TCZ-IV in combination with MTX or as monotherapy (ACT-RAY) and in those who received TCZ-IV or ADA as monotherapy (ADACTA). Conclusion: Patients with long-standing, severe RA who received IV or SC TCZ as monotherapy or in combination with csDMARDs had improvement in physical function and disease activity at Week 12 that was maintained at Week 24. Overall, across all the trials, response to treatment was associated with improvement in physical function. Acknowledgments : This study was sponsored by Genentech, Inc. Support for third-party writing assistance, furnished by Health Interactions, Inc, was provided by Genentech, Inc. Disclosure of Interests: : Sebastian Unizony Grant/research support from: Genentech, Inc., Joseph Dang Shareholder of: Genentech, Inc., Employee of: Genentech, Inc., Jian Han Shareholder of: Genentech, Inc., Employee of: Genentech, Inc., Margaret Michalska Shareholder of: Genentech, Inc., Employee of: Genentech, Inc., Jennie H. Best Shareholder of: Genentech, Inc., Employee of: Genentech, Inc.

Objective. To assess differences in joint damage and inflammation using magnetic resonance imaging (MRI) between patients with rheumatoid arthritis (RA) who achieved low disease activity with tocilizumab (TCZ) + methotrexate (MTX) and subsequently continued or discontinued MTX. Methods. In the COMP-ACT trial, US patients with RA received subcutaneous TCZ 162 mg + MTX. Those who achieved 28-joint count Disease Activity Score calculated with erythrocyte sedimentation rate (DAS28-ESR) ≤ 3.2 at Week 24 were randomized 1:1 (double-blind) to discontinue MTX (TCZ monotherapy; mono) or continue TCZ + MTX until Week 52. In a subset of patients, 1.5-Tesla MRI was used to obtain images of bilateral hands and wrists at weeks 24 and 40. Outcomes included changes in MRI-assessed synovitis, osteitis, erosion, and cartilage loss from Week 24 to Week 40, and in the proportion of patients with progression of each score. Results. Of 296 patients who achieved DAS28-ESR ≤ 3.2 at Week 24, 79 were enrolled in the pilot MRI substudy and randomized to TCZ mono (n = 38) or TCZ + MTX (n = 41). Treatment with either TCZ mono or TCZ + MTX suppressed erosion progression, synovitis, osteitis, and cartilage loss. The proportion of patients with no progression in each outcome measure was similar between groups (range, TCZ mono: 84.8–97.0%; TCZ + MTX: 92.3–100%). Conclusion. In a subset of patients who achieved low disease activity with TCZ + MTX, MRI changes were minimal in intraarticular inflammation and damage measures in patients who discontinued MTX versus those who continued TCZ + MTX.

Background: In patients with RA, subcutaneous tocilizumab (TCZ-SC) is administered every 2 weeks (q2w) or every week (qw), based on the patient’s weight and clinical response. Objectives: To compare the effects on disease activity at week 24, when the dosing schedule of TCZ-SC was escalated from q2w to qw, in patients who did not achieve LDA (DAS28-ESR > 3.2) at week 12 in COMP-ACT with patients who, despite not achieving LDA, continued TCZ-SC qw in SUMMACTA and q2w in BREVACTA. Methods: US patients in COMP-ACT who weighed < 100 kg at baseline and who received TCZ-SC 162 mg q2w + methotrexate escalated to qw if they did not achieve LDA at week 12. DAS28-ESR remission (< 2.6) and LDA (≤ 3.2), CDAI remission (≤ 2.8) and LDA (≤ 10) and SDAI remission (≤ 3.3) and LDA (≤ 11) at week 24 were compared between patients who switched from q2w to qw and North American patients in SUMMACTA who initiated TCZ qw + csDMARDs and continued a qw dose (baseline body weight < 100 kg and DAS28 > 3.2 at week 12). A secondary analysis compared COMP-ACT patients who escalated from q2w to qw with all SUMMACTA patients who continued a qw dose and all BREVACTA patients who initiated a TCZ-SC q2w dose + csDMARDs and continued a q2w dose (baseline body weight < 100 kg and DAS28 > 3.2 at week 12). DAS28 was standardized to DAS28-ESR, and comparisons were calculated using a mixed model with repeated-measures logistic regression, including the following covariates: CDAI, SDAI and/or DAS28 at the reference visit (week 12), as well as study baseline values of CDAI, SDAI and/or DAS28, baseline age, sex, TNFi use prior to the study (yes or no) and weight category. Results: A total of 328 US patients in COMP-ACT did not achieve LDA at week 12 and escalated from q2w to qw TCZ-SC. In SUMMACTA, 285 patients did not achieve LDA at week 12 and continued TCZ-SC qw, of whom 71 were from North America. Baseline demographic and clinical characteristics were comparable between patients in COMP-ACT and North American patients in SUMMACTA. A significantly higher proportion of patients in COMP-ACT achieved DAS28-ESR, CDAI and SDAI remission and LDA 12 weeks after TCZ dose escalation (week 24) than North American SUMMACTA patients (Table 1). Similar results were seen when the proportion of patients who achieved DAS28 remission and LDA was compared at week 24 between patients in COMP-ACT and patients from all geographic regions who did not escalate dosing in SUMMACTA and BREVACTA (N=196). Conclusion: US patients with RA who did not achieve LDA and escalated from q2w to qw TCZ-SC at week 12 in COMP-ACT had better disease activity outcomes at week 24 than North American patients who did not achieve LDA and continued qw dosing in SUMMACTA. These results provide some evidence that escalation from q2w to qw has more effect than expected without dose change for patients who do not achieve LDA by week 12. Table 1. Comparison at Week 24 of Clinical Response After Week 12 Dose Escalation or Continuation Between Patients Who Did Not Achieve LDA at Week 12 All COMP-ACT (N = 328 ) North American SUMMACTA (n = 71 ) All SUMMACTA (N = 285 ) All BREVACTA (N = 196 ) DAS28-ESR remission, n (%) 66 (20.1) 7 (9.9) 44 (15.4) 36 (18.4) Adjusted OR (95% CI) Ref 5.76 (1.92, 17.32) 3.29 (2.11, 5.12) 2.35 (1.44, 3.84) P value Ref 0.0018 < 0.0001 0.0006 DAS28-ESR LDA, n (%) 122 (37.2) 17 (23.9) 90 (31.6) 60 (30.6) Adjusted OR (95% CI) Ref 3.36 (1.61, 7.00) 2.81 (1.97, 4.01) 2.24 (1.50, 3.33) P value Ref 0.0012 < 0.0001 < 0.0001 CDAI remission, n (%) 12 (3.7) 2 (2.8) 13 (4.6) 11 (5.6) Adjusted OR (95% CI) Ref 4.50 (1.32, 15.32) 2.93 (1.37, 6.27) 1.45 (0.69, 3.05) P value Ref 0.0161 0.0056 0.3325 CDAI LDA, n (%) 80 (24.4) 11 (15.5) 81 (28.4) 66 (33.7) Adjusted OR (95% CI) Ref 4.19 (1.88, 9.35) 2.35 (1.63, 3.39) 1.32 (0.88, 1.97) P value Ref 0.0005 < 0.0001 0.1825 SDAI remission, n (%) 16 (4.9) 2 (2.8) 15 (5.3) 11 (5.6) Adjusted OR (95% CI) Ref 5.23 (1.44, 19.01) 3.23 (1.54, 6.76) 1.64 (0.81, 3.30) P value Ref 0.0120 0.0019 0.1670 SDAI LDA, n (%) 89 (27.1) 11 (15.5) 91 (31.9) 72 (36.7) Adjusted OR (95% CI) Ref 4.68 (2.20, 9.99) 2.20 (1.56, 3.11) 1.47 (0.99, 2.17) P value Ref < 0.0001 < 0.0001 0.0540 Acknowledgements: This study was funded by Genentech, Inc. Support for third-party writing assistance, furnished by Health Interactions, Inc., was provided by Genentech, Inc. Disclosure of Interests: Nora Singer Grant/research support from: Genentech/Roche, Merck and Pfizer, Shalini Mohan Shareholder of: Genentech, Inc., Employee of: Genentech, Inc., Jian Han Shareholder of: Genentech, Inc., Employee of: Genentech, Inc., Michael Edwardes Employee of: Everest Clinical Research, Margaret Michalska Shareholder of: Genentech, Inc., Employee of: Genentech, Inc.

Background Oral glucocorticoids (OGC) have been the mainstay of treatment for giant cell arteritis (GCA). However, OGCs are associated with several adverse events (AEs). Objectives To estimate the risk of potential OGC-related AEs in patients with GCA. Methods This retrospective, observational cohort study utilized the 2008-2017 IBM Explorys Electronic Health Records database which includes lab values. Inclusion criteria included age ≥ 50 years with ≥ 2 GCA diagnoses ≥ 7 days apart, 1 OGC prescription within 6 months of the first GCA diagnosis (index date = date of first OGC prescription) followed by a second OGC prescription, no other autoimmune disease requiring high-dose OGCs, no exposure to anti-tumor necrosis factor or anti-interleukin-6 therapies, ≥ 1 C-reactive protein (CRP)/erythrocyte sedimentation rate (ESR) lab test and 12 months of data available pre- and post-index. Potential AEs assessed during the 12 months post-index were descriptively summarized across cohorts of patients based on quartiles (Q) of mean daily dose of OGCs measured over 6 months post-index among this patient sample (Q1: ≥ 1.00 to ≤ 13.75 mg; Q2: > 13.75 to ≤ 25.00 mg; Q3: > 25.00 to ≤ 40.00 mg; Q4: > 40.00 mg). Potential AEs included type 2 diabetes (T2D) diagnosis, hemoglobin A1c (HbA1c), blood glucose level, serious infections, cataracts, gastrointestinal bleeding or ulcer and increases in body mass index (BMI). Actual OGC use by patient could not be confirmed and is a limitation of this study. Results Mean age of the 785 eligible patients was 76 years (SD 9); 70% were female. Mean Deyo Charlson Comorbidity Index score at baseline was 1.57 (SD 2.01). The most common baseline comorbid conditions were cerebrovascular disease, diabetes, chronic pulmonary disease, and renal disease. Mean daily OGC dose was 28.9 mg during the first 6 months post-index. Mean (SD) CRP and ESR during the 12-month follow-up was 5.1 (13.6) and 26.5 (20.7), respectively. The proportion of patients with newly diagnosed T2D or with HbA1c ≥ 7.5 during the 12-month follow-up ranged from 7.5% to 24.5% from OGC daily dose Q1 to Q4 cohorts. The proportion of patients with glucose ≥ 200 mg/dL ranged from 7.5% to 15.0% from Q1 to Q4. Serious infections ranged from 16.8% to 24.8% from Q1 to Q4 and cataract ranged from 12.0% to 21.7% from Q1 to Q4. The proportions of patients with gastrointestinal bleed/ulcer ranged from 6.0% in Q1 to 11.8% in Q4. An increase in BMI of 5 ranged from 4.1% to 6.4% from Q1 to Q4. Conclusion In patients with GCA, potential OGC-related AEs increased with increased daily OGC dose. This highlights the need for effective therapies that reduce the exposure and potential risk of OGCs. Acknowledgement This work was supported by funding from Genentech, Inc Disclosure of Interests Jennie H. Best Shareholder of: Genentech, Employee of: Genentech, Amanda M. Kong Employee of: IBM Watson Health, Oth Tran Employee of: IBM Watson Health, Margaret Michalska Employee of: Genentech, Inc.

Objective To quantify the healthcare expenditures associated with potential oral glucocorticoid (OGC)-related adverse events (AEs) in patients with giant cell arteritis (GCA). Methods Patients with GCA and ≥ 1 OGC prescription fill between 2009 and 2014 were identified from the MarketScan Commercial and Medicare Supplemental claims databases. Patients were stratified into four groups based on cumulative OGC dose (> 0 to ≤ 2607 mg, > 2607 to ≤ 4800 mg, > 4800 to ≤ 7200 mg, and > 7200 mg) during the 1-year follow-up period; incidence of potential AEs and AE-related direct healthcare costs in USD were assessed. Association between the log of cumulative OGC dose and AE-related direct healthcare costs was evaluated, adjusting for baseline characteristics. Results Of 1602 patients with GCA included, 69% were women; the mean age was 73 years. The mean cumulative OGC dose was 5806 mg during the 1-year follow-up; most exposure occurred in the first 6 months. The proportion of patients with potential OGC-related AEs was 36.5% overall and increased as cumulative dose increased (30.7%–45.3% across dose groups). Unadjusted mean AE-related costs for patients with an AE was USD $12,818. In the multivariable model including all patients, increasing OGC dose was associated with increasing AE-related healthcare costs (cost ratio, 1.38 [95% CI, 1.16–1.64] per 1-unit increase in log of cumulative OGC dose [P < 0.001]). Mean (median)-predicted AE costs for the dose groups were USD $4389 ($2749) for > 0 to ≤ 2607 mg, USD $5176 ($3009) for > 2607 to ≤ 4800 mg, USD $5576 ($3633) for > 4800 to ≤ 7200 mg, and USD $6609 ($4447) for > 7200 mg. Conclusion In patients with GCA, OGC-related AEs increased with increasing cumulative OGC dose, resulting in increased healthcare costs. These results highlight the need for efficacious therapies that reduce the exposure to and potential risks associated with OGCs.

Jennie H Best Amanda M Kong 2 David M Smith Ibrahim Abbass Margaret Michalska 1Genentech, Inc., South San Francisco, CA, USA; 2IBM Watson Health, Cambridge, MA, USA Objective: To quantify the healthcare expenditures associated with potential oral glucocorticoid (OGC)-related adverse events (AEs) in patients with giant cell arteritis (GCA). Methods: Patients with GCA and ≥ 1 OGC prescription fill between 2009 and 2014 were identified from the MarketScan Commercial and Medicare Supplemental claims databases. Patients were stratified into four groups based on cumulative OGC dose (> 0 to ≤ 2607 mg, > 2607 to ≤ 4800 mg, > 4800 to ≤ 7200 mg, and > 7200 mg) during the 1-year follow-up period; incidence of potential AEs and AE-related direct healthcare costs in USD were assessed. Association between the log of cumulative OGC dose and AE-related direct healthcare costs was evaluated, adjusting for baseline characteristics. Results: Of 1602 patients with GCA included, 69% were women; the mean age was 73 years. The mean cumulative OGC dose was 5806 mg during the 1-year follow-up; most exposure occurred in the first 6 months. The proportion of patients with potential OGC-related AEs was 36.5% overall and increased as cumulative dose increased (30.7%–45.3% across dose groups). Unadjusted mean AE-related costs for patients with an AE was USD $12,818. In the multivariable model including all patients, increasing OGC dose was associated with increasing AE-related healthcare costs (cost ratio, 1.38 [95% CI, 1.16–1.64] per 1-unit increase in log of cumulative OGC dose [P < 0.001]). Mean (median)-predicted AE costs for the dose groups were USD $4389 ($2749) for > 0 to ≤ 2607 mg, USD $5176 ($3009) for > 2607 to ≤ 4800 mg, USD $5576 ($3633) for > 4800 to ≤ 7200 mg, and USD $6609 ($4447) for > 7200 mg. Conclusion: In patients with GCA, OGC-related AEs increased with increasing cumulative OGC dose, resulting in increased healthcare costs. These results highlight the need for efficacious therapies that reduce the exposure to and potential risks associated with OGCs.

BackgroundGiant cell arteritis (GCA) is the most common form of vasculitis. Diagnosis is difficult due to multiple presenting symptoms: headache, jaw and limb claudication, myalgia and visual impairment. Access to care may be delayed because often multiple providers are involved in the diagnosis of GCA and disease management. Treatment with high-dose glucocorticoids (GCs) can relieve symptoms and prevent vision loss, but GC-related adverse events are common; GCA often relapses once GCs are tapered.ObjectivesTo understand the GCA patient care pathway and unmet needs in GCA through in-depth patient interviews.MethodsUS patients with GCA were recruited through outreach to physicians and The Vasculitis Foundation, which used email newsletters and social media to recruit ≈ 50% of participating patients. Extensive individual interviews with patients were conducted by qualitative researchers by phone or in person and explored patients’ perspectives and experiences from the onset of GCA symptoms to diagnosis and disease management. Patients were asked open-ended questions and encouraged to share their stories to provide additional insights into the patient journey and their individual perspectives. The qualitative data collected were analyzed using human-centered design methodology, including patient typologies (personas: optimist, fearful, stoic or despondent), forced temporal zoom (journey maps), forced semantic zoom (stakeholder system mapping) and affinity mapping for pattern recognition of unmet needs.ResultsA total of 28 patients were interviewed; 23 (82%) were women and mean age was 69 years (Table). The number of patients in each persona category is shown in the Table. Stoic and optimist personas had medium to high levels of self-advocacy and a positive/engaged attitude about their condition, while fearful and despondent personas had low levels of self-advocacy with disengaged/negative attitudes toward their condition. Patients often ascribed their milder GCA symptoms to causes such as stress and did not consult a physician until they developed moderate to severe symptoms, such as persistent headache, jaw pain or visual disturbances. Patients with existing inflammatory disorders were less likely to share symptoms of GCA unless the symptoms substantially worsened. In most cases, physicians diagnosed GCA based on abnormal erythrocyte sedimentation rate, often followed by a temporal artery biopsy. After diagnosis of GCA, all patients received GCs with little information on the chronicity of GCA. Few patients were offered treatment alternatives to GCs. Overall, patients managed their GCA independently, with moderate support from friends or family, and sought to balance relief of GCA symptoms with the adverse effects of GCs. Patients concentrated on tapering and discontinuing GCs, with less concern about relapse. Furthermore, patients who were most uncomfortable with the adverse effects of GCs often waited until their GCA symptoms became debilitating before telling their physician. Almost all patients reported searching for a support group after the diagnosis.ConclusionPatients with GCA experience adverse effects from GCs and remain focused on reducing their GC dose. For those with inflammatory comorbidities, diagnosis of GCA is another burden in a debilitating journey that results in a sense of disempowerment and resignation toward their condition and paucity of therapeutic options. Patients with GCA want a clearer understanding of treatment options and need access to support groups. Patients’ attitudes and self-advocacy vary depending on their personas; recognizing these personas may help HCPs coordinate patient care. Increased awareness of GCA among patients and HCPs may accelerate the path to diagnosis and treatment, and emerging therapies may help reduce GC burden.AcknowledgementThis study was funded by Genentech, Inc.Disclosure of InterestsJennie H. Best Shareholder of: Genentech, Employee of: Genentech, Ivan Nunez Employee of: Azul Seven, Kristina Woodburn Employee of: Azul Seven, Abby Breyer Employee of: Azul Seven, Mike Conway Employee of: Azul Seven, Margaret Michalska Employee of: Genentech, Inc.

Background For patients with giant cell arteritis (GCA) and/or polymyalgia rheumatica (PMR), glucocorticoids are the mainstay of treatment. However, due to the chronic nature of these diseases, patients may require continued glucocorticoid treatment to achieve treatment targets or prevent disease relapse, over time resulting in high cumulative doses and associated adverse events. Objectives To assess patterns of glucocorticoid use and outcomes in patients with GCA, PMR or both. Methods This retrospective cohort study used electronic medical records from a single US community-based rheumatology clinic utilizing the JointMan rheumatology software application. Patients age ≥ 50 years with a diagnosis of either GCA or PMR and ≥ 1 entry for glucocorticoid following the diagnosis were included and followed until lost to follow-up or the end of the study period (30 Nov 2017). The index date was defined as the date of first glucocorticoid prescription received at or after the earliest GCA or PMR diagnosis date. Outcomes at 2 years included the proportion of patients achieving remission (defined as not receiving steroids for ≥ 6 months), time to remission, persistence of remission (defined as not receiving steroids for ≥ 6 months and still not receiving steroids at 2 years) and prednisone dose at follow-up, and were compared between patients with GCA only, PMR only or both GCA and PMR. P values are reported using F-test (ANOVA) for continuous variables and Chi-squared test for categorical variables. Results We identified 81 patients with GCA only, 779 with PMR only and 97 with GCA and PMR. Mean (SD) age was 70.0 (9.1) years; 64.2% were women. Mean (SD) daily prednisone dose at the index date was 46.7 (30.9) mg for patients with GCA only, 20.1 (14.2) for PMR only and 29.0 (23.4) for patients with both GCA and PMR. Two years after the index date, 32% of patients with GCA only, 32% with PMR only and 27% with GCA and PMR had achieved remission; 17%, 23% and 18% were in persistent remission, respectively (Table 1), with no significant differences between groups. Among patients who achieved remission, overall median time to first remission was 202.5 (0-635) days and was shorter for patients with both GCA and PMR (157 [0-619] days) vs GCA (213 [0-577] days) or PMR (203.5 [0-635] days) only. Kaplan-Meier estimates of time to remission for each group are shown (Figure 1). Most patients required a daily prednisone dose at 2 years, with similar doses observed between groups (Table 2). Conclusion Patients with either GCA and/or PMR are exposed to significant doses of prednisone. In this study, fewer than one-third of patients with GCA and/or PMR achieved remission; the majority of patients continued to require prednisone therapy for at least 2 years after its initiation. These data highlight the need for the use of more efficacious and steroid-sparing therapies in patients with GCA and/or PMR. Disclosure of Interests Gary Craig Shareholder of: co-owner of Arthritis NW, PLLC and Discus Analytics, LLC, Consultant for: advisory board for Premera Blue Cross, Speakers bureau: Bristol-Myers Squibb, Eli Lilly, Genentech, Celgene, AbbVie, Novartis, and Sandoz, Keith Knapp Employee of: Discus Analytics, Bob Salim Employee of: Axio Research, Shalini Mohan Shareholder of: Genentech, Inc., Employee of: Genentech, Inc, Margaret Michalska Employee of: Genentech, Inc.

BackgroundPatients with rheumatoid arthritis (RA) often receive methotrexate (MTX) in combination with biologics; however, MTX may be discontinued due to intolerance or to reduce the medication burden once disease control is achieved. Whereas previous studies have established the efficacy of tocilizumab (TCZ) initiated as monotherapy (MONO) for the treatment of RA,1,2 patient-reported outcomes (PROs) after MTX withdrawal in patients achieving good clinical response to TCZ +MTX have not been evaluated. PROs are important measures when determining response to therapy in patients with RA with respect to health-related quality of life (HRQOL).3,4ObjectivesThis study evaluated PROs between patients with RA who achieved low disease activity with TCZ +MTX and then continued or discontinued MTX in the COMP-ACT trial (NCT01855789).MethodsUS patients with RA who were inadequate responders to MTX were enrolled; initial combination therapy included MTX (≥15 mg/week orally) plus TCZ 162 mg subcutaneous either weekly (qw) or every 2 weeks (q2w). Patients who achieved DAS28-ESR≤3.2 at Week 24 were randomised 1:1 to receive TCZ-MONO or continue TCZ +MTX until week 52 (double-blind). Changes in PRO scores were measured between Week 24 and Weeks 40 and 52, and included patient global assessment of disease activity (PtGA; visual analogue score [VAS], 0–100 mm), pain (VAS), Health Assessment Questionnaire Disability Index (HAQ-DI, 0–3) and Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue.ResultsOf the 296 randomised patients (TCZ +MTX, n=148; TCZ-MONO, n=148), 74.8% were women, mean age was 55.5 years, mean RA duration was 6.8 years and mean DAS28-ESR was 6.3 at baseline. At Week 24 (randomization), PRO scores were similar between the randomised treatment groups. The mean changes in PtGA, pain, HAQ-DI and FACIT-fatigue scores from Week 24 to Weeks 40 were similar between the TCZ +MTX and TCZ-MONO groups (table 1). The proportion of patients with HAQ-DI <0.5 was similar between the groups at Week 24 (randomization), and remained similar at Weeks 40 and 52.ConclusionsPatients receiving TCZ who discontinue MTX appear to have similar PROs across multiple measures compared with patients continuing TCZ +MTX. Differences observed in clinical parameters between TCZ-MONO and TCZ +MTX did not appear to achieve a threshold that would be considered clinically meaningful. Similarities in PROs on both treatments were consistent with the clinical efficacy measures previously reported from COMP-ACT.References[1] Jones G, et al. J Rheumatol2017;44(2):142–6. [2] Dougados M, et al. Ann Rheum Dis. 2013;72(1):43–50. [3] Deshpande PR, et al. Perspect Clin Res. 2011;2(4):137–44. [4] Her M, Kavanaugh A. Curr Opin Rheumatol. 2012;24(3):327–34.AcknowledgementsThis study was funded by Genentech, Inc.Disclosure of InterestJ. Kremer Shareholder of: Corrona, LLC, Consultant for: Abbvie, Amgen, Bristol-Myers Squibb, Eli Lilly and Company, Genentech, GlaxoSmithKline, Pfizer, Regeneron and Sanofi, W. Rigby Consultant for: Roche/Genentech, N. Singer Grant/research support from: Merck/EMD Serono (in kind lab resources) and unrestricted educational grants from several companies to MetroHealth for 2016 Cleveland Society of Rheumatology, C. Birchwood Employee of: Genentech, Inc., D. Gill Employee of: Genentech, Inc., W. Reiss Employee of: Genentech, Inc., J. Best Employee of: Genentech, Inc., J. Pei Employee of: Genentech, Inc., M. Michalska Employee of: Genentech, Inc.

Objective Randomised controlled trials (RCTs) have shown tocilizumab (TCZ) administered intravenously or subcutaneously with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) to be superior to csDMARDs alone for improving rheumatoid arthritis (RA) disease activity. This study evaluated the effect of TCZ-intravenous and TCZ-subcutaneous on patient-reported outcomes (PROs) in three RCT populations. Methods OPTION ( NCT00106548 ), BREVACTA ( NCT01232569 ) and SUMMACTA ( NCT01194414 ) were independent RCTs evaluating the efficacy and safety of TCZ-intravenous and/or TCZ-subcutaneous with csDMARDs in patients with RA. PROs included patient global assessment, pain, Health Assessment Questionnaire-Disability Index, Functional Assessment of Chronic Illness Therapy-Fatigue and Short Form-36. Study outcomes included the proportions of patients reporting changes from baseline in PRO scores ≥ minimum clinically important differences (MCID) and scores ≥ age and gender-matched normative values. Results In OPTION, more patients who received TCZ-intravenous reported improvements in PROs ≥MCID (50%–82% vs 31%–57%) and scores ≥ normative values (16%–44% vs 5%–28%) at week 16 compared with placebo. Similarly, a greater proportion of patients in BREVACTA who received TCZ-subcutaneous reported improvements ≥ MCID (54%–73% vs 42%–55%) and scores ≥ normative values (8%–34% vs 4%–25%) at week 12 compared with placebo. In SUMMACTA, 61%–84% of patients who received TCZ-subcutaneous and 64%–84% of those who received TCZ-intravenous reported improvements ≥ MCID and 14%–41% and 15%–24%, respectively, scores ≥ normative values at week 24. Conclusions TCZ-intravenous or TCZ-subcutaneous with csDMARDs resulted in more patients reporting clinically meaningful improvements and PRO scores ≥ normative values compared with placebo. These improvements were similar with TCZ-intravenous and TCZ-subcutaneous.

Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are two related forms of systemic vasculitis. Patients with these conditions often experience relapses affecting various body systems. Here we describe rates of relapse and review healthcare costs resulting from relapse among patients with GPA/MPA. Two groups of patients with GPA and MPA were selected from the MarketScan claims databases between 2011 and 2013 based on diagnosis codes. Patients were followed for 12 months to identify relapses based on an algorithm of diagnoses in medical and medication claims. Relapses were categorized into one of the following groups: renal relapse, pulmonary relapse, other relapse-associated condition relapse, GPA or MPA utilization relapse, and mixed relapse. The final sample of patients with GPA and MPA consisted of 2707 and 740 patients, respectively. In both groups, approximately one-quarter of patients experienced relapse during the 12-month follow-up period. The mean all-cause healthcare costs in the 4-month period after relapse were $38,313 (SD, $54,120) for patients with GPA and $35,947 (SD, $48,065) for patients with MPA. In both groups, renal relapses were the costliest. Costs during the 4 months immediately following relapses were substantially higher than what could be expected over a 4-month follow-up among patients who did not experience relapse based on 12-month all-cause costs (GPA, $32,005 [SD, $64,570]; MPA, $61,044 [SD, $125,093]). Relapses are common among patients with GPA and MPA, and treatment of relapses can be costly. More effective therapies are needed to prevent relapses. Genentech, Inc.

BackgroundSerum levels of C-X-C motif chemokine ligand 13 (CXCL13) and soluble intercellular adhesion molecule-1 (sICAM-1) have been associated with response to tocilizumab (TCZ) in patients with rheumatoid arthritis (RA); levels of matrix metalloproteinase-3 (MMP-3) and S100A8/A9 have also been associated with RA disease activity and joint damage.ObjectivesTo evaluate the association of CXCL13, sICAM-1, MMP-3 and s100A8/A9 levels with disease activity and response to TCZ in patients with RA who achieved low disease activity with 24 weeks of TCZ + methotrexate (MTX) treatment and were subsequently randomized to TCZ monotherapy (mono) or TCZ + MTX in the COMP-ACT trial (NCT01855789).MethodsUS patients with RA who had an inadequate response to MTX received initial combination therapy of MTX plus TCZ 162 mg subcutaneous for 24 weeks. Patients who achieved Disease Activity Score in 28 joints calculated with erythrocyte sedimentation rate (DAS28-ESR) ≤ 3.2 at Week 24 were randomized 1:1 (double-blind) to receive either TCZ mono or continue TCZ + MTX until Week 52. Randomized patients were included in the present study based on baseline, Week 24 and Week 40 sample availability; serum levels of CXCL13, sICAM-1, MMP-3 and S100A8/A9 were measured by immunoassay. Correlations between CXCL13, sICAM-1, MMP-3 and S100A8/A9 levels and DAS28-ESR at baseline, Week 24 and Week 40 were determined according to Spearman correlation coefficient. Changes in CXCL13, sICAM-1, MMP-3 and S100A8/A9 levels from baseline to Week 24 (open-label period) were determined using Wilcoxon test. Mean changes in CXCL13, sICAM-1, MMP-3 and S100A8/A9 levels from Week 24 to Week 40 (randomized period) were compared between treatment arms using analysis of covariance.ResultsOf 296 randomized patients, 249 were included (TCZ mono, n = 126; TCZ + MTX, n = 123). Biomarker levels were well balanced across treatment arms at baseline and Week 24 (randomization). At baseline, there were weak to mild correlations between DAS28-ESR and biomarker levels (CXCL13 [r = 0.13, P = 0.0411], sICAM-1 [r = 0.20, P = 0.0015], MMP-3 [r = 0.19, P = 0.0021], S100A8/A9 [r = 0.25, P = 0.0001]). Significant reductions in mean biomarker levels were observed from baseline to Week 24 (open-label period) among the total randomized patients (P < 0.0001). CXCL13, sICAM-1, MMP-3 and S100A8/A9 levels were relatively stable between Week 24 and Week 40 (randomized period), with no significant differences between TCZ mono and TCZ + MTX (Table).ConclusionIn agreement with previous studies, the association between baseline disease activity and CXCL13, sICAM-1, MMP-3 and S100A8/A9 levels was weak to mild; TCZ + MTX treatment from baseline to Week 24 (open-label period) resulted in significant reductions in all biomarkers. Changes in levels of CXCL13, sICAM-1, MMP-3 and S100A8/A9 from Week 24 to 40 (randomized period) were similar between treatment groups, consistent with the finding of non-inferiority of TCZ mono compared with TCZ + MTX in patients with RA who achieve low disease activity with TCZ + MTX.AcknowledgementThis study was funded by Genentech, Inc.Disclosure of InterestsD. James Haddon Shareholder of: Stockholder of Genentech/Roche, Employee of: Employee of Genentech/Roche, Thierry Sornasse Employee of: Genentech, Inc., Michael J. Townsend Shareholder of: Stockholder of Genentech/Roche, Employee of: Genentech/Roche, Jinglan Pei Employee of: Genentech, Margaret Michalska Employee of: Genentech, Inc.

To quantify the healthcare expenditures associated with oral glucocorticoids-related-adverse events (OGCs-AEs), among patients in the US with giant cell arteritis (GCA) using claims data from MarketScan® Commercial and Medicare Supplemental Databases. Patients age ≥50 years with GCA and at least one OGC prescription fill, during 1/1/2009-6/30/2014 (first OGC claim after GCA diagnosis date = index date) were selected. Cumulative dose of OGCs was measured during the 1-year post-index period. Patients were stratified in four cohorts (>0-≤2,607 mg, >2,607-≤4,800 mg, >4,800-≤7,200 mg, >7,200 mg) based on the distribution of OGC exposure. Incidence of potential AEs and AE-related direct healthcare costs (2016 USD) were also assessed during the 1-year post-index period. A generalized linear model with log link and gamma distribution was used to evaluate the association between the log of cumulative dose of OGCs and AE-related direct healthcare costs, adjusting for baseline characteristics. RESULTS The 1,602 GCA patients (mean age, 73, 69% females) had a mean cumulative OGC dose post-index of 5,806 mg (median=4,800 mg), with most exposure occurring in the first 6 months. The proportion of patients with any potential OCGs-AEs was 36.5% overall (n=584) and increased as cumulative dose increased (30.7%-45.3% across quartiles). Unadjusted mean AE costs for patients with an AE was $12,818 (median=$1,844). In the multivariable model, increasing OGC dose was associated with increasing AE-related healthcare costs (cost ratio=1.38 (95% CI 1.16-1.64) per 1 unit increase in log(cumulative OGC dose), p<0.001). Mean (median) predicted AE costs for the dosing quartiles were: $4,389 ($2,749) for >0-≤2,607 mg, $5,176 ($3,009) for >2,607-≤4,800 mg, $5,576 ($3,633) for >4,800-≤7,200 mg, $6,609 ($4,447) for >7,200 mg. Rates of OGCs-AEs tended to increase with an increase in cumulative OGC dose, which resulted in increased healthcare costs. These results highlight the need for efficacious therapies that reduce the exposure and potential risks with OGCs.

Background Tocilizumab (TCZ) is a recombinant humanized monoclonal antibody targeted against the interleukin-6 receptor that was approved to treat rheumatoid arthritis (RA) in the EU in 2009 and in the US in 2010. TCZ has now completed long-term extension (LTE) follow-ups in a number of intravenous and subcutaneous RA trials. Objectives To provide an updated report on the incidence of safety events during TCZ treatment in patients with RA using data from multiple completed clinical trials and their LTEs, as well as to provide an update from the global TCZ postmarketing safety database. Methods Incidence and reporting rates of adverse events (AEs) of special interest, including infections, malignancies, anaphylaxis, bleeding events, myocardial infarctions, gastrointestinal perforations, strokes, hepatic events and demyelination, were estimated from 2 distinct patient data sets. Incidence rates were calculated from 12 completed TCZ RA clinical trials and their LTE periods and are reported as events per 100 patient-years (PY). Reporting rates were also estimated from the global TCZ postmarketing safety database (Oct 2008 to Oct 2015), which includes information from all spontaneously reported cases and non-interventional programs as well as literature cases, and are reported as cases per 100 patients. Results The clinical trial all-exposure population consisted of 7647 TCZ-treated patients with RA (81.6% female; mean [SD] age, 52 [12.6] years), constituting 22,394 PY (mean follow-up, 2.93 years) of exposure. The overall rate (95% CI) of serious AEs in the clinical trial population was 14.16 (13.67–14.66) per 100 PY. Overall incidence rates for individual events for the clinical trial population are reported in the Table and were consistent in each 6-month period over the 5-year duration. The global postmarketing population included 606,937 patients. The overall spontaneous reporting rate (range) of AEs of special interest in the postmarketing population was 9.37 (7.35–10.56) cases per 100 patients. Reporting rates of individual safety events of interest in the global postmarketing population are shown in the Table and were consistent in each 6-month period over the 7-year duration. Conclusions The safety profile of TCZ in the current analysis, which includes information about safety events from 12 clinical trials and their LTEs and across 7 years of real-world postmarketing reports encompassing $≈ $ 600,000 patients, was consistent with previous safety reports. These findings are consistent with the previously reported profile of TCZ and indicate that there is no evidence of increased safety risk with increasing exposure to TCZ. Acknowledgements This study was funded by F. Hoffmann-La Roche/Genentech, Inc. Disclosure of Interest S. Mohan Employee of: Genentech, Inc., M. Michalska Employee of: Genentech, Inc., J. Yourish Employee of: Genentech, Inc., J. Pei Employee of: Genentech, Inc., S. Gale Employee of: Genentech, Inc., C. Birchwood Employee of: Genentech, Inc., E. Berber Employee of: Genentech, Inc.

ObjectiveTo evaluate whether tocilizumab (TCZ) monotherapy is noninferior to treatment with TCZ plus methotrexate (MTX) for maintaining clinical responses in patients with rheumatoid arthritis (RA) in whom low disease activity is achieved with TCZ plus MTX.MethodsPatients with RA who experienced an inadequate response to MTX received MTX plus TCZ 162 mg subcutaneously. At 24 weeks, patients who achieved a Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28‐ESR) of ≤3.2 were randomized to receive TCZ monotherapy or to continue treatment with TCZ plus MTX until week 52. The primary outcome measure was the comparison of the mean change in the DAS28‐ESR from week 24 to week 40 between the TCZ monotherapy and TCZ plus MTX arms (noninferiority margin of 0.6). Secondary outcome measures included worsening of the DAS28‐ESR by ≥1.2, achievement of a DAS28‐ESR of <2.6 and ≤3.2, and safety and immunogenicity.ResultsAmong the 718 patients enrolled, 296 were randomized at week 24 to receive TCZ monotherapy (n = 147) or TCZ plus MTX (n = 147). The mean changes in the DAS28‐ESR from week 24 to week 40 were 0.46 and 0.14 in the TCZ monotherapy arm and the TCZ plus MTX arm, respectively (weighted difference between the groups, 0.318 [95% confidence interval 0.045, 0.592]); discontinuing MTX in TCZ responders was noninferior to continuing MTX. Safety events were broadly similar between the randomized treatment groups; the most common serious adverse event was infection, which occurred in 2.1% of patients in the TCZ monotherapy group and 2.2% of patients receiving TCZ plus MTX.ConclusionPatients with RA receiving TCZ plus MTX who achieve low disease activity can discontinue MTX without significant worsening of disease activity during the 16 weeks following MTX discontinuation.

Objective Two randomised controlled trials, AMBITION (NCT00109408) and ADACTA (NCT01119859), showed tocilizumab (TCZ) monotherapy superior to methotrexate (MTX) and adalimumab (ADA) monotherapy, respectively, for improving rheumatoid arthritis (RA) disease activity. This study compared the benefit of TCZ versus MTX or ADA monotherapy for improving patient-reported outcomes (PROs) in patients with RA. Methods PROs included patient global assessment (PtGA), pain, Health Assessment Questionnaire Disability Index (HAQ-DI), Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue and Short Form-36 (SF-36) physical component summary (PCS) and mental component summary (MCS) and eight domain scores. Outcomes included proportions of patients reporting changes from baseline in PRO scores >= minimum clinically important differences (MCID) and >= age-matched and gender-matched normative values at 24 weeks. Results In AMBITION, TCZ-treated patients reported significantly greater mean improvements in HAQ (-0.7 vs -0.5), FACIT-Fatigue (8.7 vs 5.7), SF-36 PCS (9.8 vs 7.8) and five SF-36 domains at week 24 than with MTX; 45.0%-84.0% of TCZ-treated patients reported improvements >= MCID, and 24.3%-52.1% reported scores >= normative values across all PROs versus 39.4%-81.8% and 14.5%-45.0%, respectively, with MTX. In ADACTA, TCZ-treated patients reported significantly greater improvements in PtGA (-42.3 vs -31.8), pain (-40.1 vs -28.7), SF-36 MCS (7.9 vs 5.0) and three SF-36 domains than with ADA; 57.7%-83.3% of TCZ-treated patients reported improvements >= MCID, and 22.1%-49.3% reported scores >= normative values across all PROs versus 13.6%-37.8%, respectively, with ADA. Conclusions TCZ monotherapy resulted in more patients reporting clinically meaningful PRO improvements and PRO scores >= normative values compared with MTX or ADA monotherapy.