Sari Greenberg-Dotan

Systemic Therapy for Psoriasis and the Risk of Herpes Zoster: A 500 000 Person-year Study

IMPORTANCE The risk for herpes zoster (HZ) in patients with psoriasis treated with biologic medications or other systemic treatments has been given little attention to date. OBJECTIVE To describe the risk for HZ in patients with psoriasis and its relation to treatment. DESIGN, SETTING, AND PARTICIPANTS A cohort study was performed using the administrative database of Clalit Health Services, the largest public health care provider organization in Israel, in the setting of general community clinics, primary care and referral centers, and ambulatory and hospitalized care. We extracted information for all patients who received a psoriasis diagnosis from January 2002 to June 2013. Follow-up was conducted until the end of July 2013. The study included 95,941 patients with psoriasis in the analysis, with 522,616 person-years of follow-up. Incidence of HZ events was calculated for each systemic antipsoriatic medication provided, during a follow-up period of 11 years and 7 months. We used a generalized estimating equation Poisson regression model to examine the effect of each systemic treatment for psoriasis on HZ incidence, adjusting for age, sex, psoriasis severity, Charlson comorbidity index, steroid treatment, and socioeconomic status. MAIN OUTCOMES AND MEASURES Incidence of HZ associated with systemic therapies. RESULTS In a multivariate analysis, it was observed that treatment with phototherapy (rate ratio [RR], 1.09 [95% CI, 0.62-1.93]; P = .99), methotrexate (RR, 0.98 [95% CI, 0.78-1.23]; P = .83), cyclosporine (RR, 1.16 [95% CI, 0.48-2.80]; P = .49), and biologic medications as a single agent (RR, 2.67 [95% CI, 0.69-10.3]; P = .14) was not associated with HZ. The use of combination treatment with biologic medications and methotrexate was significantly associated with an increased incidence of HZ (RR, 1.66 [95% CI, 1.08-2.57]; P = .02). The use of acitritin was associated with decreased incidence of HZ (RR, 0.69 [95% CI, 0.49-0.97]; P = .004). CONCLUSIONS AND RELEVANCE Physicians may need to consider offering an HZ preventive vaccine to patients receiving combination treatment with biologic medications and methotrexate, particularly if they have additional risk factors for HZ.

Psoriatic arthritis treatment and the risk of herpes zoster

Objectives To study the association between traditional disease-modifying antirheumatic drugs (c-DMARD) or anti-TNF-α agents and herpes zoster (HZ) in patients with psoriatic arthritis (PsA). Methods A retrospective cohort study was conducted in patients with PsA between 2002 and 2013. Patients were grouped as follows: no DMARDs (Group A); c-DMARDs (Group B); anti-TNF-α agents (Group C); anti-TNF-α agents in combination with c-DMARDs (Group D). Crude incidence rates (IR) were calculated as number of HZ episodes per 1000 patient-years. A Cox regression model was used to adjust for HZ risk factors (age, gender, steroid use, Charlson Comorbidity Index score, and previous treatment) in order to estimate their contribution to the risk of the first HZ event. Results The study included 3128 patients, mean age 50.26±14.54 years; 46.2% male. During a period of 20 096 person-years 182 HZ events were observed. The crude IR (95% CI) of HZ in the study population was 9.06 per 1000 patient-years, and in Groups A-D 7.36 (5.41 to 9.79), 9.21 (7.5 to 11.21), 8.64 (4.84 to 14.26), 17.86 (10.91 to 27.58), respectively. In a multivariate analysis, age (HR 1.01, 95% CI 1.00 to 1.02), treatment with steroids (HR 1.08, 95% CI 1.04 to 1.13), and a combination of anti-TNF-α agents and c-DMARDs (HR 2.37, 95% CI 1.32 to 4.22) were significantly associated with HZ events. Conclusions In our database, the risk of HZ was significantly increased with age, treatment with steroids, and combination of anti-TNF-α agents and c-DMARDs, but not with c-DMARDs or anti-TNF-α therapy alone. Time to HZ event was shorter in patients treated with anti -TNF-α agents.

The 'real-life' impact of adding bevacizumab to first-line therapy in metastatic colorectal cancer patients: a large Israeli retrospective cohort study.

Abstract Background. After a decade of extensive use, the actual contribution of bevacizumab in first-line treatment of metastatic colorectal cancer (mCRC) is still unclear. Objective. To evaluate ‘real-life’ outcomes of patients with mCRC before and after the introduction of bevacizumab to standard mCRC first-line practice. Methods. Using the computerized administrative database of Clalit Health Services’ (CHS), Israels largest health care provider, we retrospectively compared two cohorts (n = 1739): (A) all CHS’ patients diagnosed with mCRC between January 2000 and December 2004 that received first-line irinotecan or oxaliplatin-based combination chemotherapy (before bevacizumab was introduced) (n = 1052), and (B) all patients that started first-line irinotecan or oxaliplatin combination chemotherapy together with bevacizumab between September 2006 and December 2009 (after bevacizumab was fully reimbursed in Israel for mCRC first-line therapy) (n = 687). The primary endpoint was overall survival (OS) and secondary endpoints were first-line progression-free survival (PFS) and metastatectomy rates. Results. Median OS was longer in Cohort B than in Cohort A [23.0 months vs.15.0, adjusted hazard ratio (HR), 0.75]. Secondary outcomes were also better; PFS of 14.0 months vs. 9.8 in the earlier period (HR, 0.75) and metastatectomy rate of 8.1% versus 3.9%. The longer OS in Cohort B was preserved even after controlling for latter-line epidermal growth factor receptor (EGFR) inhibitor use (HR = 0.77). Conclusion. In this analysis, OS, PFS and metastatectomy rates of first-line treatment of mCRC were significantly higher in the later period of the study. These results, derived from ‘real-life’ practice, suggest that the use of bevacizumab, among other alterations in the clinical management of mCRC between the two periods, might have had a significant contribution to these outcomes, and may therefore support the current practice of adding bevacizumab to first-line treatment of mCRC.

The ESMO-Magnitude of Clinical Benefit Scale for novel oncology drugs: correspondence with three years of reimbursement decisions in Israel

ABSTRACT Background: The European Society for Medical Oncology published in 2015 its Magnitude of Clinical Benefit Scale (ESMO-MCBS) for cancer medicines. Our objective was to evaluate the association between Israel’s national reimbursement decisions regarding novel cancer drugs, prior to the availability of ESMO-MCBS, and the later published ESMO-MCBS scores. Research design and methods: ESMO-MCBS scores were obtained retrospectively for the cancer drugs that were candidates for reimbursement in Israel in 2013–2015 and were categorized to ‘highest benefit’ (ESMO-MCBS 4–5 or A) ‘medium benefit’ (3 or B) and ‘lowest benefit’ (0–2 or C). The reimbursement decisions were accessed and compared with the categorized ESMO scores. Results: ESMO-MCBS score was available for 19/22 drugs approved for reimbursement and 15/16 non-approved drugs. 58% of the approved drugs gained a ‘highest benefit’ score and 37% were ‘medium benefit’. 87% of the non-approved drugs had ‘lowest benefit’ scores. Median score for approved drugs was 4 vs. 1 for the non-approved (p < 0.05). Conclusions: The Israeli decisions regarding reimbursement of novel cancer drugs, demonstrated concordance with ESMO-MCBS scores. Incorporation of ESMO-MCBS data in reimbursement deliberations could assist in framing the appropriate use of the limited resources to deliver effective and affordable cancer care.

Second-Line Treatment of Her2-Positive Metastatic Breast Cancer: Trastuzumab beyond Progression or Lapatinib? A Population Based Cohort Study

Background The relative efficacy of lapatinib vs. continuing trastuzumab beyond progression (TBP) in HER2-positive metastatic breast cancer (MBC) patients, who progressed on first-line trastuzumab, is still unclear. The objective of this population based cohort study was to compare outcomes of lapatinib vs. TBP in daily practice. Methods All HER2-positive MBC patients who began second-line anti HER2 therapy between 1st January 2010 and 30th August 2013 were selected from Clalit Health Services’ (CHS) electronic database. Available data on patient and disease characteristics and treatments were analyzed. The primary endpoint was overall survival (OS). Outcomes were compared using the Kaplan-Meier (log-rank) method and Cox proportional hazards model. Results 64 patients received second-line lapatinib and 93 TBP. The two treatment groups were similar in age and co-morbidity rates, but differed in proportion of prior adjuvant trastuzumab (lapatinib: 29.7%, TBP: 16.1%, P = 0.043) and rates of prior brain metastases (lapatinib: 32.8%, TBP: 10.8%, P = 0.01). Lapatinib median OS was 13.0 months (95% CI: 9.5–16.5) vs. 31.0 for TBP (95% CI: 20.6–41.4), P<0.001. On multivariate analysis, longer OS was preserved for TBP, after controlling for differences in age, adjuvant trastuzumab, duration of first-line trastuzumab therapy, brain metastases, visceral metastases and hormonal treatment [Hazard Ratio (HR) = 0.63, 95% CI: 0.40–0.99, P = 0.045]. Conclusion In this comparative cohort study, OS of HER2-positive MBC patients treated with TBP was significantly longer than with lapatinib. These results might be especially relevant in settings where ado-trastuzumab-emtansine (TDM-1), the current preferred agent in this setting, is not available yet for patients.

SAT0378 Cardiac and Cardiovascular Morbidities in Patients with Psoriatic Arthritis: A Population-Based Cohort Study

Background Psoriatic arthritis (PsA) is associated with higher prevalence and risk for cardiovascular morbidities [1,2]. Objectives The aim of the study is to substantiate these findings in our population and to examine additional aspects of cardiovascular morbidities, including congestive heart failure and cardiomyopathy. Methods A retrospective, longitudinal, cohort case control study was performed on records of patients with PsA between 2000 and 2013 from the database of Israels largest health care provider, Clalit Health Services. For each patient with PsA, 5 control patients without history of psoriasis or rheumatoid arthritis were chosen, matched for age and gender. The following morbidities were analyzed: ischemic heart disease (IHD), valvular heart disease excluding mitral valve prolapse, congestive heart failure (CHF), cardiomyopathy, idiopathic hypertrophic subaortic stenosis (IHSS), cerebrovascular accident (CVA), carotid artery disease, peripheral vascular disease (PVD), and aortic aneurism. T-test was used to compare continuous variables and Chi square test was used for categorical variables. Age, gender, socioeconomic status and ethnicity were entered into a multivariate regression model. Results The study included 3161 patients with PsA, 1474 males (46.6%) and 1687 (53.4%) females with a mean age of 58.29±15.44 years, and 15,805 controls. Comparative analysis demonstrated higher prevalence of the following in the case cohort: IHD (18.95% vs. 14.49%) p<0.0001, valvular heart disease (6.99% vs. 5.10%) p<0.0001, CHF (5.98% vs. 4.61%) p<0.001, cardiomyopathy (1.28% vs. 0.80%) p<0.010, carotid artery disease (2.53% vs. 1.99%) p=0.053. and peripheral vascular disease (4.87% vs. 3.68%) p=0.001. Prevalence of IHSS, CVA and aortic aneurism were not significantly higher in the patients compared with the control group. The following were significantly more prevalent in patients than controls in multivariate regression analysis model: IHD (P<0.0001), CHF (P<0.0001), cardiomyopathy (p=0.011), and PVD (p=0.001) valvular heart disease (P<0.0001); and there was a trend to higher prevalence of carotid artery disease in PsA patients (p=0.066). Conclusions A high prevalence of cardiovascular co-morbidities was found in this cohort of PsA patients. The spectrum of cardiac involvement was not limited to IHD, carotid artery disease and PVD, and included also increased risk of CHF, cardiomiopathies and valvular heart disease. A high index of suspicion, and close monitoring and treatment of cardiovascular risk factors are recommended. References Husni ME, Mease PJ. Managing comorbid disease in patients with psoriatic arthritis. Curr Rheumatol Rep 2010;12:281–287. Horreau C, Pouplard C, Brenaut E, Barnetche T, Misery L, Cribier B, et a l. Cardiovascular morbidity and mortality in psoriasis and psoriatic arthritis: a systematic literature review. J Eur Acad Dermatol Venereol 2013;27(Suppl. 3):12–29. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3830