Enhanced therapeutic efficacy of doxorubicin/cyclophosphamide in combination with pitavastatin or simvastatin against breast cancer cells.

Fighting breast tumors mandates finding different agents devoid of chemotherapy side effects. Repurposing existing drugs, such as statins, presents a promising avenue for the development of novel cancer therapeutics. Based on the different effects of statin members, this study aims to evaluate the effect of two of the most promising lipophilic statins, Simvastatin and Pitavastatin, and their combination with a conventional chemotherapeutic regimen of doxorubicin and cyclophosphamide on breast cancer cells. MDA-MB-231 and MCF7 cell lines were used to analyze the effects of Pitavastatin and simvastatin in combination with doxorubicin/cyclophosphamide. Cell viability and cell cycle were analyzed and certain apoptosis-related genes such as Bax, Bcl2, and caspase-3, besides cyclin D1 were analyzed using qPCR. The viability of breast cancer cells decreased significantly after treatment with a doxorubicin/cyclophosphamide combination in the presence of Pitavastatin or simvastatin compared with dual doxorubicin/cyclophosphamide with a higher effect in MDA-MB-231 cells than MCF7. In MDA-MB-231, The triple combination of Pitavastatin or simvastatin with doxorubicin/cyclophosphamide resulted in an increase in the expression levels of apoptotic markers than treatment with doxorubicin/cyclophosphamide combination (Bax (p-value = 0.09& 0.02, respectively), Bax/Bcl2 ratio (p-value = 0.0002& <0.0001, respectively)). However, the increase in caspase3 wasn't significant (p-value = 0.45& 0.09, respectively). Moreover, the expression of cyclin D1 decreased (p-value = 0.0002& <0.0001, respectively) and the cell cycle was arrested in the G1 phase. Combination of Pitavastatin or simvastatin with doxorubicin/ cyclophosphamide may induce apoptosis in breast cancer cells via upregulation of the Bax/Bcl2 pathway, potentially providing a promising new therapeutic strategy for breast cancer.

Effectiveness, safety, and cost of vancomycin and linezolid in Kuwait: A retrospective cohort study.

Background: The effectiveness, safety, and cost of vancomycin and linezolid for managing gram-positive bacterial infections in Kuwait are unknown. This study assessed the effectiveness, safety, and cost of vancomycin, teicoplanin and linezolid for managing gram-positive bacterial infections in Kuwait. Research design and methods: This retrospective study included adult patients who were prescribed antibiotics (vancomycin, teicoplanin, and linezolid) for the treatment of gram-positive infections at five hospitals in Kuwait. Descriptive statistics were used to assess the effectiveness and safety outcomes. A cost analysis was performed on the patients hospitalised for gram-positive infections. Results: Among 116 patients, 42.2 % (n = 49) received glycopeptides (vancomycin [n = 45] and teicoplanin [n = 4]) or linezolid (n = 67). Clinical cure was achieved in 100 patients without significant intergroup differences (p = 0.34). Thrombocytopenia and acute kidney injury occurred in 19 and 20 patients (p = 0.82 and 0.96), respectively, and their incidence was similar with all the studied agents. The average cost per patient was USD 983.70. The estimated total direct medical costs were USD 894,570.6, the cost was highest for linezolid (USD 469,682.30) and vancomycin (USD 370,342.5), and lowest for teicoplanin (USD 20,799.9). Conclusions: Glycopeptides and linezolid were highly effective. Linezolid was the most frequently prescribed agent; its effectiveness and safety were similar according to the antibiotic class. However, treatment with linezolid and vancomycin were associated with considerable costs.

Efficacy of montelukast as an adjuvant therapy in rheumatoid arthritis patients: A randomized controlled study.

OBJECTIVE: This study aimed to evaluate the efficacy of montelukast in conjunction with non-biologic disease modifying anti-rheumatic drugs (nDMARDs) in rheumatoid arthritis (RA) patients. METHODS: This study was a single-center randomized double-blinded placebo-controlled study. Adult RA patients were included if they had moderate to severe disease activity and were receiving monotherapy or combination of nDMARDs. Eligible patients were randomized, in 1:1 ratio, to receive either 10 mg montelukast or placebo, once daily for 16 weeks. The primary endpoint was the change in the 28-joints disease activity score (DAS28) 16 weeks after treatment. The patients' quality of life (QoL) was assessed by the Arabic version of the Health Assessment Questionnaire-Disability Index. Moreover, serum levels of vascular adhesion molecule-1 (VCAM-1) were measured. RESULTS: A total of 87 patients completed the study; 44 in the montelukast arm and 43 in the control arm. After 16 weeks of treatment, disease activity decreased significantly in the montelukast arm with mean change in DAS28 (95% CIs) of -1.5 (-1.7, -1.2) while the control arm showed no improvement (0.2 (0.0, 0.4), p < 0.01). The QoL of the patients improved significantly from baseline in the montelukast arm (p < 0.01) but not in the control arm (p = 0.08). The median (IQR) serum levels of VCAM-1 were significantly lower in the montelukast arm (22.8 (15.0-32.7)) than in the control arm (28.9 (15.4-42.8), p = 0.004). CONCLUSION: The co-administration of montelukast with nDMARDs in RA patients enhanced the anti-rheumatic effect which was reflected clinically by decreased disease activity.

Efficacy of metformin in prevention of paclitaxel-induced peripheral neuropathy in breast cancer patients: a randomized controlled trial.

Background: Paclitaxel-induced peripheral neuropathy (PN) is a serious clinical problem with no approved drug for prevention. This study aimed to examine the neuroprotective effect of metformin against paclitaxel-induced PN in breast cancer patients. Methods: Patients with confirmed breast cancer diagnosis who were planned to receive paclitaxel were randomized to receive either metformin or placebo. Both groups received the standard chemotherapy protocol for breast cancer. Patients started metformin/placebo 1 week before paclitaxel initiation and continued study interventions thereafter for nine consecutive weeks. The primary outcome was the incidence of development of grade two or more paclitaxel-induced sensory PN. The PN was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). Patients' quality of life (QoL) was assessed by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACTGOG-Ntx) subscale. Pain severity was measured by the Brief Pain Inventory Short Form (BPI-SF). Serum levels of nerve growth factor (NGF) and neurotensin (NT) were measured at baseline and at the end paclitaxel treatment. Results: A total of 73 patients (36 in the metformin arm and 37 in the control arm) were evaluated. The cumulative incidence of development of grade two or more PN was significantly lower in the metformin arm (14 (38.9%) than the control arm (28 (75.7%); p = 0.001). At the end of paclitaxel treatment, patients' QoL was significantly better in the metformin arm [median (IQR) FACTGOG-Ntx subscale of (24.0 (20.5-26.5)] compared to the control arm (21.0 (18.0-24.0); p = 0.003). The metformin arm showed lower "average" and "worst" pain scores than those detected in the control arm. At the end of the paclitaxel treatment, there was a significant difference in the median serum NGF levels between the two arms, favoring metformin (p < 0.05), while NT serum levels were deemed comparable between the two study arms (p = 0.09). Conclusion: The use of metformin in breast cancer patients offered a marked protection against paclitaxel-induced PN, which translated to better patient QoL. Clinical Trial Registration: https://classic.clinicaltrials.gov/ct2/show/NCT05351021, identifier NCT05351021.

Cyclophosphamide with cyclosporine A for graft-versus-host disease prophylaxis in adult patients with acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation from human leucocyte antigen-matched donors.

BACKGROUND: Graft-versus-host disease (GVHD) is one of the most severe complications in patients with acute myeloid leukemia (AML) who underwent allogenic hematopoietic stem cell transplantation (HSCT). This study addressed the effectiveness and safety outcomes of high dose post-transplant cyclophosphamide (PT-CY) followed by cyclosporine A (CSA) as a GVHD prophylaxis protocol. PATIENTS AND METHODS: From January 2019 to March 2021, AML patients who underwent HSCT, and received high-dose PT-CY followed by CSA were prospectively recruited, assessed, and followed up for one-year post-transplantation (PT). The cumulative incidences of both acute GVHD (aGVHD) at 100 days PT, and chronic GVHD (cGVHD) at one-year PT were assessed. RESULTS: This study included 52 patients. The cumulative incidence (95% CIs) of aGVHD was 2.3% (0.3 - 15.4%), while the cumulative incidence of cGVHD was 23.2% (12.2-41.5%). The cumulative incidence of relapse and non-relapse mortality were 15.6%, and 7.9%, respectively. The median duration to reach neutrophil and platelet engraftment was 17 and 13 days, respectively. The overall, progression-free, and GVHD-free/relapse-free survival rates (95% CIs) were 89.6% (76.6 - 95.6%), 77.7% (62.1-87.5%), and 58.2% (41.6 - 71.7%) respectively. The cumulative incidences of the main transplant-related complications were; neutropenic sepsis (48.3%), cytomegalovirus reactivation (21.7%), pneumonia (13.8%), hemorrhagic cystitis (17.8%), septic shock (4.9%), and CSA toxicity (48.9%). CONCLUSION: PT-CY followed by CSA was associated with low cumulative incidences of both aGVHD and cGVHD without increase in either the relapse or transplant-related complications; so, considered as a promising protocol to be widely applied in the settings of HLA-matched donors.

Effect of concomitant use of pitavastatin with neoadjuvant chemotherapy protocols in breast cancer patients: A randomized controlled clinical trial.

Introduction: Preclinical studies have demonstrated the possible anticancer effects of statins, but the synergistic effect of concomitant statin use with standard chemotherapy protocols in patients with breast cancer has not yet been investigated. Aim: The current study aimed to evaluate the efficacy of concomitant pitavastatin use with neoadjuvant chemotherapy protocols in patients with breast cancer. Methods: This study was a randomized controlled clinical trial. A total of 70 adult female patients with pathologically-proven invasive breast cancer were randomized to receive or not receive pitavastatin (2 mg) oral tablets once daily concomitantly with standard neoadjuvant chemotherapy protocols for 6 months. The primary outcomes of this study were changes in tumor size and changes to the Ki67 index. In addition, secondary outcomes were changes in cyclin D1 and cleaved caspase-3 serum levels. This study was registered at ClinicalTrials.gov (Identifier: NCT04705909). Results: Patients in the pitavastatin group showed significantly higher median (IQR) reductions in tumor size [-19.8 (-41.5, 9.5)] compared to those in the control group [-5.0 (-15.5, 0.0), p = 0.0009]. The change in Ki67 from baseline to the end of therapy was similar between the two groups (p = 0.12). By the end of therapy, the cyclin D1 levels in the pitavastatin group were significantly decreased [median (IQR) change of - 10.0 (-20.2, -2.9) from baseline], whereas the control group showed an increase in cyclin D1 levels [14.8 (4.1, 56.4)]. The median (IQR) caspase-3 was elevated in the pitavastatin group 1.6 (0.2, 2.2), and decreased in the control group (-0.2 (-1.1, 0.0), p = 0.0002).Subgroup analysis of the pitavastatin group revealed that patients with positive human epidermal growth receptor 2 (HER2) had higher median (IQR) reductions in Ki67 [-35.0 (-70.0, -12.5)] than those with negative HER2 [2.5 (-15.0, 10.0), p = 0.04]. All patients who achieved a complete pathological response (n = 9) exhibited an HER2-neu positive receptor at baseline. Conclusion: Concomitant use of pitavastatin with standard neoadjuvant chemotherapy protocols may improve neoadjuvant chemotherapy responses in patients with breast cancer.

Efficacy and Safety of Neostigmine Adjunctive Therapy in Patients With Sepsis or Septic Shock: A Randomized Controlled Trial.

Background: Neostigmine has been found to improve survival in animal models of sepsis. However, its feasibility, efficacy, and safety in patients with sepsis or septic shock have not been investigated. Aim: This parallel randomized controlled double-blinded design aimed to investigate the efficacy and safety of neostigmine as an adjunctive therapy in patients with sepsis or septic shock. Patients and Methods: A total of 167 adult patients with sepsis or septic shock were assessed for eligibility; 50 patients were randomized to receive a continuous infusion of neostigmine (0.2 mg/h for 120 h; neostigmine arm) or 0.9% saline (control arm) in addition to standard therapy. The primary outcome was the change in Sequential Organ Failure Assessment (SOFA) scores 120 h after therapy initiation. Secondary outcomes included mortality rates and changes in procalcitonin level. Results: The median (interquartile range) change in SOFA scores improved significantly in the neostigmine arm [-2 (-5, 1)] as compared with the control arm [1.5 (0, 2.8); p = 0.007]. Progression from sepsis to septic shock was more frequent in the control arm (p = 0.01). The incidence of shock reversal in patients with septic shock was significantly lower in the control arm than in the neostigmine arm (p = 0.04). Differences in 28-days mortality rates did not reach statistical significance between the control and neostigmine arms (p = 0.36). Percentage change in procalcitonin levels was similar in both arms (p = 0.74). Conclusion: Neostigmine adjunctive therapy may be safe and effective when administered in patients with sepsis or septic shock. Clinical Trial Registration: NCT04130230.

Effect of Anti-Inflammatory and Antimicrobial Cosupplementations on Sepsis Prevention in Critically Ill Trauma Patients at High Risk for Sepsis.

Background: Sepsis development in patients with trauma is associated with bad prognosis. This study investigated the effect of immunomodulatory interventions in major trauma patients at high risk for sepsis. Methods: In a randomized, double-blinded, controlled design, severe trauma patients were stratified by leukocyte anti-sedimentation rate (LAR) test into high risk (HR) and low risk (LR) for sepsis. The HR patients were randomly allocated into intravenous vitamin C plus vitamin B1 (HR-CB), intramuscular vitamin D plus oral Lactobacillus probiotics (HR-DP), or control (HR-C) groups. The clinical trial was registered at clinicaltrials.gov (https://clinicaltrials.gov/show/NCT04216459). Outcomes: The primary outcome was Acute Physiologic Assessment and Chronic Health Evaluation score II (APACHE II) score. Secondary outcomes included sepsis incidence, changes in Sequential Organ Failure Assessment (SOFA) score, and serum monocyte chemoattractant protein-1 (MCP-1) on day 6 from baseline, 28-day mortality, intensive care unit (ICU), and hospital discharge. Results: The HR-DP, HR-CB, and LR groups showed a significantly lower incidence of sepsis development (20%, 20%, and 16%, respectively, versus 60% in the HR-C group, p-value = 0.004). The three groups also showed a significant improvement in APACHE II and SOFA scores. Besides, MCP-1 levels were significantly decreased in HR-DP and HR-CB groups compared to the HR-C group (p-value ≤ 0.05). Significantly decreased mortality (10% and 16% versus 60% in the HR-C group) and increased ICU discharge (95% and 84% versus 45% in the HR-C group) were observed in HR-CB and LR groups (p-value = 0.001). Conclusion: Both combinations of interventions improved APACHE II scores and reduced sepsis incidence in trauma patients. The LAR combined with injury severity score were good sepsis predictors.

Acceptance of illness and need for education to support dermatology self-care in psoriasis patients: a cross-sectional study.

INTRODUCTION: Acceptance of illness greatly affects the quality of life of psoriatic patients. Assessment of patients' need for education and support is very important for patients' counselling and follow-up. AIM: To evaluate acceptance of illness and need for education to support dermatology self-care in Arabic patients with psoriasis. MATERIAL AND METHODS: A cross-sectional study using a survey was conducted. The survey collected patients' demographics, disease characteristics, Acceptance of Illness Scale (AIS) and Person-Centered Dermatology Self-Care Index (PeDeSI). Outcome measures were presented in total and in relation to age, gender, disease duration, disease severity, quality of life and level of education. The correlation between AIS and PeDeSI was examined using Spearman's rank correlation test. RESULTS: In total, 209 psoriatic patients from 12 Arabic countries participated in the survey with mean ± SD age of 35.8 ±10.0 years. The median (IQR) AIS score was 28 (19-35). The median (IQR) of the PeDeSI score was 15 (11-22). Both AIS and PeDeSI did not differ in relation to age, gender, disease duration, and level of education. However, patients with a higher impairment in quality of life reported lower levels of illness acceptance (p = 0.001) and a higher need for education and support (p = 0.004). AIS and PeDeSI were moderately correlated (rho = 0.33, p < 0.001). CONCLUSIONS: Arabic psoriatic patients showed moderate acceptance of illness and required some education to support dermatology self-care. Greater clinical attention with focus on patient education and counselling should be given to Arabic patients with psoriasis especially those with more impaired quality of life.

Depressive, anxiety, stress, and insomnia symptoms in patients with psoriasis: a cross-sectional study.

INTRODUCTION: Assessment of psychological well-being in psoriasis patients is recommended. However, studies evaluating depressive, anxiety, stress, and insomnia symptoms in Arabic patients with psoriasis are lacking. AIM: To quantify levels of psoriasis-related depressive, anxiety, stress, and insomnia symptoms in Arabic patients with psoriasis. MATERIAL AND METHODS: A cross-sectional survey on patients' demographics, disease characteristics, and psychological measures using the Patient Health Questionnaire-9, Generalized Anxiety Disorder 7-item scale, Depression Anxiety Stress Scale-21 (7-item stress subscale), and Insomnia Severity Index. The prevalence and scores of depressive, anxiety, stress, and insomnia symptoms were calculated. Multivariate linear regression models were developed to assess patients' demographics and disease characteristics affecting the psychological measures. RESULTS: The analysis included 223 patients. The patients reported mild levels of depressive, anxiety, and insomnia symptoms (median (interquartile range (IQR)) scores: 9 (6-14), 6 (4-11), and 12 (4-18), respectively) and a moderate level of stress symptoms (median (IQR) score: 10 (5-14)). The prevalence of depressive, anxiety, stress, and insomnia symptoms were 47.1%, 32.7%, 59.6%, and 57%, respectively. Multivariate linear regression analyses revealed that for each unit increase in the impact of psoriasis on daily life, there were 5.7 (95% confidence intervals (CI): 3.7-7.8), 3.8 (95% CI: 1.8-5.7), 5.3 (95% CI: 3.1-7.4), and 6.5 (95% CI: 3.7-9.4) units increase in depression, anxiety, and stress, and insomnia scores, respectively. CONCLUSIONS: The prevalence of depressive, anxiety, stress, and insomnia symptoms in Arabic patients with psoriasis was high. Clinical interventions, screening for psychiatric comorbidities, and consideration of psychotherapy should be implemented in this patient group.

Arabic Translation and Validation of the Acceptance of Illness Scale and Person-Centered Dermatology Self-care Index.

OBJECTIVE: To translate the Acceptance of Illness Scale (AIS) and Person-Centered Dermatology Self-care Index (PeDeSI) from English to Arabic and validate their use among Arabic-speaking patients with psoriasis. METHODS: Forward-backward translation was used to translate AIS and PeDeSI from English to Arabic language. Validation of the developed Arabic versions was performed using a cross-sectional study design. Arabic-speaking psoriatic patients were asked to complete the Arabic AIS and PeDeSI tools. Patients were also asked to complete the Dermatology Life Quality Index (DLQI), which was used as a reference to study external validity. The correlation between questionnaires was tested using Spearman rank correlation test. Factor analysis was used to study the dimensionality of the various tools. Cronbach α coefficient was used to evaluate internal consistency of Arabic versions of AIS and PeDeSI. Floor or ceiling effects were detected if more than 15% of patients achieved the lowest or the highest possible scores, respectively. RESULTS: A total of 116 Arabic patients with psoriasis submitted the questionnaires. Both translated questionnaires were unidimensional. The internal consistencies of the AIS and PeDeSI were excellent (α coefficient = .90) and good (α coefficient = .87), respectively. There was a significant negative moderate correlation between the AIS and DLQI (ρ = -0.44), whereas the PeDeSI and DLQI were significantly weakly correlated (ρ = -0.23). No floor or ceiling effects were detected. CONCLUSIONS: The results suggest that the Arabic versions of the AIS and PeDeSI questionnaires fulfilled the criteria for validation and may be used in research and routine clinical practice with Arabic speakers.

Feeling of stigmatization and satisfaction with life among Arabic psoriatic patients.

BACKGROUND: Satisfaction and stigmatization are experienced differently in different cultural contests, especially, in patients with dermatological diseases affecting visible body parts. Reports in Arabic countries remain rare and very appealing in a multicultural population. AIMS: To evaluate feeling of stigmatization and satisfaction with life in Arabic patients with psoriasis and identify predictors of feeling of stigmatization and satisfaction with life. METHODS: In a cross-sectional study design, Arabic patients with psoriasis completed the 6-item stigmatization scale and the satisfaction with life scale. Univariate and forward stepwise multivariate linear regression analyses were used to identify predictors of feeling of stigmatization and satisfaction with life. Covariates included patients' demographics (age, gender and education level), disease-related factors (disease severity, visibility, duration, and impact on quality of life) and patient-related factors (illness acceptance and dermatology self-care education level). RESULTS: In total, 199 Arabic psoriatic patients were included in the study. Despite feeling highly stigmatized by their skin disease [mean (95% Confidence Intervals (CI)) of 7.0 (6.3-7.7)], psoriasis patients were generally positive about their overall satisfaction with life (mean (95% CI) of 21.0 (20.0-22.3). Impaired quality of life was the strongest predictor of both higher feeling of stigmatization (ß-coefficient 0.39, 95% CI 0.30, 0.47) and less satisfaction with life (-0.36, 95% CI -0.53, -0.20). Higher levels of dermatology self-care education significantly predicted a lower feeling of stigmatization (-0.09, 95% CI -0.16, -0.01). Older patients (0.18, 95% CI 0.05, 0.30) and those with higher illness acceptance levels (0.14, 95% CI 0.03, 0.24) were more satisfied with life. CONCLUSIONS: A level of stigmatization was detected in most psoriatic patients including the satisfied ones. Patients with more impaired quality of life experienced higher level of stigmatization and less satisfaction with life. These findings further enforce the multidisciplinary approach in psoriatic patients and highlight the unmet need to include psychologist in the therapeutic algorithm.

Monitoring Tacrolimus Trough Concentrations During the First Year After Kidney Transplantation: A National Retrospective Cohort Study.

Background: There is a lack of data in the literature on the evaluation of tacrolimus (TAC) dosage regimen and monitoring after kidney transplantation (KT) in Kuwait. The aim of the present study was to evaluate TAC dosing in relation to the hospital protocol, the achievement of target TAC trough concentration (C0), the prevalence of TAC side effects (SEs), namely, posttransplant diabetes mellitus (PTDM), denovo hypertension (HTN), and dyslipidemia, and factors associated with the occurrence of these SEs among KT recipients. Methods: A retrospective study was conducted among 298 KT recipients receiving TAC during the first year of PT. Descriptive and multivariate logistic regression analyses were used. Results: The initial TAC dosing as per the local hospital protocol was prescribed for 28.2% of patients. The proportion of patients who had C0 levels within the target range increased from 31.5 to 60.3% during week 1 through week 52. Among patients who did not have HTN, DM, or dyslipidemia before using TAC, 78.6, 35.2, and 51.9% of them were prescribed antihypertensive, antidiabetic, and antilipidemic medications during the follow-up period. Age of ≥40 years was significantly associated with the development of de novo HTN, dyslipidemia, and PTDM (p < 0.05). High TAC trough concentration/daily dose (C0/D) ratio was significantly associated with the development of PTDM (p < 0.05). Conclusion: Less than two-fifths of patients achieved target TAC C0 levels during the first month of PT. Side effects were more common in older patients. These findings warrant efforts to implement targeted multifaceted interventions to improve TAC prescribing and monitoring after KT.

Rituximab or a second anti-tumor necrosis factor therapy for rheumatoid arthritis patients who have failed their first anti-tumor necrosis factor therapy? Comparative analysis from the British Society for Rheumatology Biologics Register.

OBJECTIVE: To compare the effectiveness of rituximab (RTX) or a second anti-tumor necrosis factor (anti-TNF) therapy in rheumatoid arthritis (RA) patients who had failed their first anti-TNF and switched to either RTX or a second anti-TNF, in routine clinical practice. METHODS: RA patients were registered with the British Society for Rheumatology Biologics Register. Response to treatment 6 months after switching was assessed using European League Against Rheumatism (EULAR) criteria and improvements in a Health Assessment Questionnaire (HAQ) score (0.22 unit or more). Regression analyses were used to compare EULAR response and improvement in HAQ score between the 2 groups, adjusting for propensity scores. RESULTS: In total, 1,328 patients were included in the analysis of EULAR response, and 937 patients were included in the analysis of HAQ scores. Six months after switching, 54.8% of patients who switched to RTX were EULAR responders compared to 47.3% of those who switched to a second anti-TNF. A total of 38.4% of RTX patients achieved a clinically important improvement in HAQ score compared to 29.6% in anti-TNF patients. After adjustment using propensity scores, patients who switched to RTX were significantly more likely to achieve EULAR response (odds ratio [OR] 1.31; 95% confidence interval [95% CI] 1.02, 1.69) compared to those who switched to an alternative anti-TNF. RTX patients were also significantly more likely to achieve improvements in HAQ score (OR 1.49; 95% CI 1.07, 2.08). CONCLUSION: The results suggest that switching to RTX may be of more benefit than switching to an alternative anti-TNF therapy after failing the first anti-TNF therapy in RA patients.

Effectiveness of rituximab in patients with rheumatoid arthritis: observational study from the British Society for Rheumatology Biologics Register.

OBJECTIVE: To assess the effectiveness of rituximab (RTX) in patients with rheumatoid arthritis (RA) in routine clinical practice, and to identify predictors of 6-month response to RTX in patients for whom at least 1 anti-tumor necrosis factor-α (anti-TNF) therapy has failed. METHOD: The analysis involved 646 patients with RA registered with the British Society for Rheumatology Biologics Register (BSRBR) who were starting RTX and were followed for at least 6 months. Change in the 28-joint Disease Activity Score (DAS28), European League Against Rheumatism (EULAR) response, and proportions of patients achieving disease remission were used to assess the clinical response 6 months after starting RTX. Regression analyses were used to identify factors associated with the response in the patients for whom anti-TNF therapy had not worked. The models included baseline demographics, disease characteristics, baseline Health Assessment Questionnaire (HAQ), and drug history including biologic history. RESULTS: The mean DAS28 at baseline was 6.2 (95% CI 6.1, 6.3), which decreased significantly to 4.8 (95% CI 4.7, 4.9) at the 6-month followup. Seventeen percent of the patients were EULAR good responders and 43% were moderate responders. Eight percent of the patients achieved disease remission. Subjects with higher baseline DAS28 score and those with positive rheumatoid factor (RF) status were significantly associated with a decrease in their DAS28 score (improvement), while women and patients with higher baseline HAQ score were less likely to improve. CONCLUSION: RTX has proven to be effective in routine clinical practice. When anti-TNF therapy fails, response to RTX was influenced by baseline DAS28 score, RF status, baseline HAQ score, and sex.

Impact of concomitant use of DMARDs on the persistence with anti-TNF therapies in patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register.

OBJECTIVE: To evaluate the effect of different concomitant disease modifying antirheumatic drugs (DMARDs) on the persistence with antitumour necrosis factor (anti-TNF) therapies in patients with rheumatoid arthritis (RA). METHOD: This analysis included 10 396 patients with RA registered with the British Society for Rheumatology Biologics Register, a prospective observational cohort study, who were starting their first anti-TNF therapy and were receiving one of the following DMARD treatments at baseline: no DMARD (n=3339), methotrexate (MTX) (n=4418), leflunomide (LEF) (n=610), sulfasalazine (SSZ) (n=308), MTX+SSZ (n=902), MTX+ hydroxychloroquine (HCQ) (n=401) or MTX+SSZ+HCQ (n=418). Kaplan-Meier survival analysis was used to study the persistence with anti-TNF therapy in each DMARD subgroup up to 5 years. Multivariate Cox proportional hazard models, stratified by anti-TNF used and start year and adjusted for a number of potential confounders, were used to compare treatment persistence overall and according to the reason for discontinuation between each of the DMARD subgroups, using MTX as reference. RESULTS: One-year drug survival (95% CI) for the first anti-TNF therapy was 71% (71% to 72%) but this dropped to 42% (41% to 43%) at 5 years. Compared with MTX, patients receiving no DMARD, LEF or SSZ were more likely to discontinue their first anti-TNF therapy while patients receiving MTX in combination with other DMARDs showed better treatment persistence. CONCLUSIONS: These results support the continued use of background DMARD combinations which include MTX. Consideration should be given to the discontinuation of LEF and SSZ monotherapy at the time anti-TNF therapies are started, with the possible exception of the SSZ+ETN combination.