Real-world Clinical Effectiveness and Safety of Vedolizumab and Adalimumab in Biologic-naive Patients With Crohn's Disease: Results From the EVOLVE Study.

GOALS: This study evaluated the real-world effectiveness and safety of vedolizumab versus adalimumab over 12 months of treatment in biologic-naive patients with Crohn's disease (CD), using data from the EVOLVE study. BACKGROUND: A comparison of vedolizumab and adalimumab may help to better position them in the therapeutic algorithm for moderate-to-severe CD. STUDY: Data were collected from medical records of patients with CD aged ≥18 years initiating treatment with adalimumab or vedolizumab between May 2014 and July 2017. Adjusted analyses were performed using inverse probability weighting to account for differences in baseline characteristics. Cumulative rates for clinical effectiveness outcomes and treatment persistence were estimated using Kaplan-Meier analyses. Disease-related exacerbations, serious adverse events (SAEs), and serious infections (SIs) were also assessed. RESULTS: Data from 218 vedolizumab- and 144 adalimumab-treated patients were analyzed. Adjusted cumulative rates of clinical remission were greater with vedolizumab than with adalimumab (66.3% vs. 46.4%; P=0.006). Probability of treatment persistence was higher with vedolizumab (89.3% vs. 77.5%; P=0.024); probabilities of clinical response (68.5% vs. 61.1%; P=0.586) and mucosal healing (67.7% vs. 56.0%; P=0.562) were similar. SAEs were less likely to occur with vedolizumab [hazard ratio, 0.45 (95% confidence interval, 0.22-0.93)]; however, the likelihood of SIs [0.27 (0.06-1.20)], CD exacerbations [0.91 (0.56-1.47)], and CD-related surgeries [1.55 (0.21-11.15)] was comparable between the 2 groups. CONCLUSIONS: In a real-world setting, biologic-naive patients with CD treated with vedolizumab demonstrated a greater likelihood of drug persistence and achieving clinical remission, with equivalent rates of response and mucosal healing versus adalimumab-treated patients.

Retrospective chart review of transplant recipients with cytomegalovirus infection who received maribavir in the Phase 3 SOLSTICE trial: Data at 52 weeks post-maribavir treatment initiation.

BACKGROUND: Cytomegalovirus (CMV) infection is a frequent complication in haematopoietic cell/solid organ transplant (HCT/SOT) recipients. Previous studies report all-cause mortality rates of 31% and 50% in HCT/SOT recipients post-treatment initiation with conventional anti-CMV therapies for refractory or resistant CMV. METHODS: This was a multi-country, retrospective medical chart review study of HCT/SOT recipients with refractory CMV infection with or without resistance (R/R) who were randomized to the maribavir arm in the open-label Phase 3 SOLSTICE trial. Patients came from 21 SOLSTICE sites across 6 countries; each site randomized ≥3 patients to the maribavir arm. Patients were followed for 52 weeks (SOLSTICE trial period: 20 weeks; follow-up chart review period: 32 weeks). The primary outcomes were mortality and graft status. RESULTS: Of 234 patients who were randomized and received maribavir in SOLSTICE, chart abstraction was completed for all 109 patients enrolled across 21 trial sites (SOT, 68/142; HCT, 41/92). At 52 weeks, overall mortality was 15.6% (17/109) and survival probability was 0.84. Among SOT recipients, survival probability was 0.96, and 3 (4.4%) deaths occurred during the chart review period. For the HCT recipients, survival probability was 0.65 with 14 (34.1%) deaths; 8 occurred during SOLSTICE and 6 during the chart review period. No new graft loss or re-transplantation occurred during the chart review period. CONCLUSIONS: Overall mortality at 52 weeks post-maribavir treatment initiation in this sub-cohort of patients from the SOLSTICE trial was lower than that previously reported for similar populations treated with conventional therapies for R/R cytomegalovirus infection.

Vedolizumab and Anti-Tumour Necrosis Factor α Real-World Outcomes in Biologic-Naïve Inflammatory Bowel Disease Patients: Results from the EVOLVE Study.

BACKGROUND AND AIMS: This study aimed to compare real-world clinical effectiveness and safety of vedolizumab, an α4ß7-integrin inhibitor, and anti-tumour necrosis factor-α [anti-TNFα] agents in biologic-naïve ulcerative colitis [UC] and Crohn's disease [CD] patients. METHODS: This was a 24-month retrospective medical chart study in adult UC and CD patients treated with vedolizumab or anti-TNFα in Canada, Greece and the USA. Inverse probability weighting was used to account for differences between groups. Primary outcomes were cumulative rates of clinical effectiveness [clinical response, clinical remission, mucosal healing] and incidence rates of serious adverse events [SAEs] and serious infections [SIs]. Secondary outcomes included cumulative rates of treatment persistence [patients who did not discontinue index treatment during follow-up] and dose escalation and incidence rates of disease exacerbations and disease-related surgeries. Adjusted analyses were performed using inverse probability weighting. RESULTS: A total of 1095 patients [604 UC, 491 CD] were included. By 24 months, rates of clinical effectiveness were similar between groups, but incidence rates of SAEs (hazard ratio [HR] = 0.42 [0.28-0.62]) and SIs (HR = 0.40 [0.19-0.85]) were significantly lower in vedolizumab vs anti-TNFα patients. Rates of treatment persistence [p < 0.01] by 24 months were higher in vedolizumab patients with UC. Incidence rates of disease exacerbations were lower in vedolizumab patients with UC (HR = 0.58 [0.45-0.76]). Other outcomes did not significantly differ between groups. CONCLUSION: In this real-world setting, first-line biologic therapy in biologic-naïve patients with UC and CD demonstrated that vedolizumab and anti-TNFα treatments were equally effective at controlling disease symptoms, but vedolizumab has a more favourable safety profile.

Physical and occupational therapy referral and use among systemic sclerosis patients with impaired hand function: results from a Canadian national survey.

OBJECTIVES: Contractures and deformities of the hand are major factors in disability and reduced health-related quality of life in systemic sclerosis (SSc). Physical (PT) and occupational therapy (OT) have been emphasised to address impaired hand function, but little is known about the extent they are employed. The objective of this study was to determine the proportion of Canadian SSc patients with hand involvement who are referred to and use PT or OT services and factors associated with referral. METHODS: Participants were respondents to the Canadian Scleroderma Patient Survey of Health Concerns and Research Priorities who rated ≥1 of 5 hand problems (hand stiffness, difficulty making fist, difficulty holding objects, difficulty opening hand, difficulty with faucet) as occurring at least sometimes with moderate or higher impact. Patients indicated if their physicians recommended PT or OT and if they used these services. Multivariate logistic regression assessed independent predictors of PT or OT referral. RESULTS: Of 317 patients with hand involvement, 90 (28%) reported PT or OT referral, but only 39 (12%) reported using these services. PT or OT referral was associated with more hand problems (odds ratio [OR]=1.24, 95% confidence interval [CI] 1.02-1.51, p=0.031) younger age (OR=0.96, 95% CI 0.94-0.99, p=0.004) and not being employed (OR=0.50, 95% CI 0.26-0.97, p=.0041). CONCLUSIONS: Few SSc patients with hand involvement are referred to PT or OT, and even fewer use these services. High-quality randomised controlled trials of PT and OT interventions to improve hand function in SSc are needed.

New directions for patient-centred care in scleroderma: the Scleroderma Patient-centred Intervention Network (SPIN).

Systemic sclerosis (SSc), or scleroderma, is a chronic multisystem autoimmune disorder characterised by thickening and fibrosis of the skin and by the involvement of internal organs such as the lungs, kidneys, gastrointestinal tract, and heart. Because there is no cure, feasibly-implemented and easily accessible evidence-based interventions to improve health-related quality of life (HRQoL) are needed. Due to a lack of evidence, however, specific recommendations have not been made regarding non-pharmacological interventions (e.g. behavioural/psychological, educational, physical/occupational therapy) to improve HRQoL in SSc. The Scleroderma Patient-centred Intervention Network (SPIN) was recently organised to address this gap. SPIN is comprised of patient representatives, clinicians, and researchers from Canada, the USA, and Europe. The goal of SPIN, as described in this article, is to develop, test, and disseminate a set of accessible interventions designed to complement standard care in order to improve HRQoL outcomes in SSc.

Is there room for criticism of studies of psychodynamic psychotherapy?

Comments on the original article, "The efficacy of psychodynamic psychotherapy," by J. Shedler (see record 2010-02208-012). Shedler declared unequivocally that "empirical evidence supports the efficacy of psychodynamic therapy" (p. 98). He did not mention any specific criticisms that have been made of evidence on psychodynamic psychotherapies or address possible distinctions between evidence for short-term versus long-term psychodynamic psychotherapies. Instead, he attributed dissenting views to biases in evidence dissemination and review, which he suggested are rooted in a "lingering distaste in the mental health professions professions for past psychoanalytic arrogance and authority" related to a "hierarchical medical establishment that denied training to non-MDs and adopted a dismissive stance toward research" (Shedler, 2010, p. 98). Shedler (2010) justified his blanket dismissal of criticisms of evidence supporting psychodynamic psychotherapy on the basis of several published meta-analyses. The validity of conclusions from metaanalyses depends on the quality of the evidence synthesized, the nature of the studies included, and the rigor of the statistical analyses employed. Many meta-analyses, however, are not performed rigorously, which can result in treatment efficacy estimates that obscure important intertrial differences and that are unlikely to be replicated in clinical practice.

Frequency and impact of symptoms experienced by patients with systemic sclerosis: results from a Canadian National Survey.

OBJECTIVE: Knowledge about the range of symptoms experienced by patients with SSc, and their impact on daily functioning is limited. The objective of the present study was to identify symptoms of SSc that patients rated as frequent and that highly impacted their ability to carry out daily activities. METHODS: A total of 464 persons with SSc responded to the Canadian Scleroderma Patient Survey of Health Concerns and Research Priorities, including questions regarding the frequency and impact of 69 SSc symptoms. Descriptive analyses were performed dichotomizing symptom frequencies as never or rarely vs sometimes, most of the time or always and symptom impact on daily activities as no or minimal impact vs moderate to severe impact. RESULTS: The five highest rated symptoms in terms of frequency and moderate to severe impact on daily activities, respectively, were: fatigue (89 and 72%), RP (86 and 67%), hand stiffness (81 and 59%), joint pain (81 and 64%) and difficulty sleeping (76 and 59%). In addition to these symptoms, items related to decreased hand function (difficulty making a fist and difficulty holding objects) and pain (muscle pain and joint tenderness) were frequently endorsed and commonly associated with moderate to severe impact on daily activities. CONCLUSION: This study confirmed the importance for quality of life of core symptoms of SSc, such as pain, fatigue and limitations in hand function. It also identified areas with very little research, such as sleep problems, that appear to play important roles in daily functioning, and that merit more focused study.

Association of pruritus with quality of life and disability in systemic sclerosis.

OBJECTIVE: To our knowledge, no studies have investigated the association of pruritus, which is present in almost half of patients with systemic sclerosis (SSc; scleroderma), with quality of life (QOL) and disability. The objective of this study was to investigate the association of pruritus with QOL and disability in SSc. METHODS: We performed a cross-sectional, multicenter study of 578 SSc patients ≥1 year post-enrollment in the Canadian Scleroderma Research Group Registry. Patients reported whether they experienced pruritus during the past month on most days and underwent clinical histories and medical examinations. QOL was measured using the mental and physical component summary scores of the Short Form 36, and disability was measured with the Health Assessment Questionnaire disability index. The association of pruritus with QOL and disability was estimated using linear regression, controlling for sociodemographic and disease variables. RESULTS: A total of 248 patients (43%) reported pruritus on most days. Patients with pruritus had significantly worse mental (Hedges's g = -0.43; 95% confidence interval [95% CI] -0.59, -0.26) and physical function (Hedges's g = -0.51; 95% CI -0.68, -0.34) and greater disability (Hedges's g = 0.46; 95% CI 0.29, 0.63) than patients without pruritus. In multivariate analyses, controlling for age, sex, marital status, education, disease duration, skin score, number of tender joints, gastrointestinal symptoms, breathing problems, Raynaud's phenomenon, and finger ulcers, pruritus was independently associated with mental (P = 0.017) and physical function (P = 0.003), but not disability (P = 0.112). CONCLUSION: Pruritus is common and associated with QOL in SSc. More attention to pruritus in SSc is needed, including its measurement, etiology, trajectory, and potential methods for intervention.

Is longer-term psychodynamic psychotherapy more effective than shorter-term therapies? Review and critique of the evidence.

BACKGROUND: In 2008, Leichsenring and Rabung performed a meta-analysis of 8 studies of longer-term psychodynamic psychotherapy (LTPP). The work was published in the Journal of the American Medical Association (vol. 300, pp 1551-1565), and they concluded that LTPP was more effective than shorter-term therapies. METHOD: Given that such claims have the potential to influence treatment decisions and policies, we re-examined the meta-analysis and the 8 studies. RESULTS: We found a miscalculation of the effect sizes used to make key comparisons. Claims for the effectiveness of LTPP depended on a set of small, underpowered studies that were highly heterogeneous in terms of patients treated, interventions, comparison-control groups, and outcomes. LTPP was compared to 12 types of comparison-controls, including control groups that did not involve any psychotherapy, short-term psychodynamic psychotherapy, and unvalidated treatments. Additionally, the studies failed to protect against threats to bias, and had poor internal validity. CONCLUSION: Overall, we found no evidence to support claims of superiority of LTPP over shorter-term methods of psychotherapy.

Prevalence and clinical correlates of pruritus in patients with systemic sclerosis.

OBJECTIVE: There are no studies of pruritus prevalence or clinical correlates in systemic sclerosis (SSc). The objectives of this study were to document the proportion of SSc patients with pruritus on most days, to determine when in the course of the disease pruritus is most prevalent, and to identify clinical correlates. METHODS: We performed a cross-sectional, multicenter study of 400 SSc patients from the Canadian Scleroderma Research Group Registry > or =1 year after Registry enrollment. Patients indicated whether they experienced pruritus during the past month on most days and underwent clinical histories and medical examinations. Multiple logistic regression was used to assess the association between sociodemographic and clinical variables and pruritus. RESULTS: A total of 179 patients (45%) reported pruritus on most days, including 69% (11 of 16) among patients 1.0-1.9 years from onset of non-Raynaud's symptoms, 41% (38 of 93) for 2.0-4.9 years, 47% (44 of 94) for 5.0-9.9 years, 43% (60 of 140) for 10.0-19.9 years, and 46% (26 of 57) for > or =20 years. In post hoc analysis, patients 1.0-1.9 years from disease onset were significantly more likely to report pruritus (P = 0.049). Patients with pruritus had significantly more skin involvement (P = 0.029), more gastrointestinal (GI) symptoms (P < 0.001), worse breathing problems (P = 0.001), worse Raynaud's symptoms (P = 0.002), and more severe finger ulcers (P = 0.009). Only the number of GI symptoms predicted pruritus in multiple logistic regression analysis (odds ratio 1.25, 95% confidence interval 1.13-1.37; P < 0.001). CONCLUSION: Pruritus is common in SSc and is independently associated with GI symptoms. Focused research on sources of pruritus and its management in SSc is needed.

Sociodemographic, disease, and symptom correlates of fatigue in systemic sclerosis: evidence from a sample of 659 Canadian Scleroderma Research Group Registry patients.

OBJECTIVE: To assess fatigue levels and demographic, socioeconomic, disease, and psychosocial correlates of fatigue in patients with systemic sclerosis (SSc). METHODS: We conducted a cross-sectional, multicenter study of 659 patients with SSc from the Canadian Scleroderma Research Group Registry. Fatigue was assessed during annual Registry visits with the Short Form 36 (SF-36) health survey vitality subscale. Patients completed measures of depressive symptoms and pain and underwent clinical histories and medical examinations. Kendall's tau was used to assess bivariate association of sociodemographic, medical, and psychosocial variables with fatigue. Multivariable associations of demographic (step 1), socioeconomic (step 2), global disease (step 3), specific disease and lifestyle (step 4), and psychosocial (step 5) factors with fatigue were assessed using hierarchical multiple linear regression. RESULTS: The mean +/- SD score of the patients on the SF-36 vitality subscale was 45.6 +/- 10.8, substantially lower (indicating more fatigue) than the mean +/- SD score for the Canadian general population (65.8 +/- 18.0). In multivariate analysis, higher fatigue was significantly associated with the number of medical comorbidities (standardized beta = -0.11, P = 0.004), breathing problems (standardized beta = -0.23, P < 0.001), the number of gastrointestinal (GI) symptoms (standardized beta = -0.27, P < 0.001), and current smoking (standardized beta = -0.08, P = 0.018). As a group, specific symptom and lifestyle variables predicted the most incremental variance in fatigue (R(2) = 21.6%, P < 0.001), despite being added to the model after demographic, socioeconomic, and global disease duration/severity indicators. Symptoms of depression (beta = -0.42) and pain (beta = -0.21) were also independently associated with fatigue (P < 0.001). CONCLUSION: High levels of fatigue are common in patients with SSc and are independently associated with clinical variables, including number of comorbidities, breathing problems, GI symptoms, and smoking.