Efficacy and safety of autologous haematopoietic stem cell transplantation versus alemtuzumab, ocrelizumab, ofatumumab or cladribine in relapsing remitting multiple sclerosis (StarMS): protocol for a randomised controlled trial.

INTRODUCTION: Autologous haematopoietic stem cell transplantation (aHSCT) is increasingly used as treatment for patients with active multiple sclerosis (MS), typically after failure of disease-modifying therapies (DMTs). A recent phase III trial, 'Multiple Sclerosis International Stem Cell Transplant, MIST', showed that aHSCT resulted in prolonged time to disability progression compared with DMTs in patients with relapsing remitting MS (RRMS). However, the MIST trial did not include many of the current high-efficacy DMTs (alemtuzumab, ocrelizumab, ofatumumab or cladribine) in use in the UK within the control arm, which are now offered to patients with rapidly evolving severe MS (RES-MS) who are treatment naïve. There remain, therefore, unanswered questions about the relative efficacy and safety of aHSCT over these high-efficacy DMTs in these patient groups. The StarMS trial (Autologous Stem Cell Transplantation versus Alemtuzumab, Ocrelizumab, Ofatumumab or Cladribine in Relapsing Remitting Multiple Sclerosis) will assess the efficacy, safety and long-term impact of aHSCT compared with high-efficacy DMTs in patients with highly active RRMS despite the use of standard DMTs or in patients with treatment naïve RES-MS. METHODS AND ANALYSIS: StarMS is a multicentre parallel-group rater-blinded randomised controlled trial with two arms. A total of 198 participants will be recruited from 19 regional neurology secondary care centres in the UK. Participants will be randomly allocated to the aHSCT arm or DMT arm in a 1:1 ratio. Participants will remain in the study for 2 years with follow-up visits at 3, 6, 9, 12, 18 and 24 months postrandomisation. The primary outcome is the proportion of patients who achieve 'no evidence of disease activity' during the 2-year postrandomisation follow-up period in an intention to treat analysis. Secondary outcomes include efficacy, safety, cost-effectiveness and immune reconstitution of aHSCT and the four high-efficacy DMTs. ETHICS AND DISSEMINATION: The study was approved by the Yorkshire and Humber-Leeds West Research Ethics Committee (20/YH/0061). Participants will provide written informed consent prior to any study specific procedures. The study results will be submitted to a peer-reviewed journal and abstracts will be submitted to relevant national and international conferences. TRIAL REGISTRATION NUMBER: ISRCTN88667898.

The efficacy of individual humanistic-experiential therapies for the treatment of depression: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating the efficacy of individual humanistic-experiential therapies (HEPs) for depression. METHOD: Database searches (Scopus, Medline, and PsycINFO) identified RCTs comparing any HEP intervention with a treatment-as-usual (TAU) control or active alternative intervention for the treatment of depression. Included studies were assessed using the Risk of Bias 2 tool and narratively synthesized. Post-treatment and follow-up effect sizes were aggregated using random-effects meta-analysis and moderators of treatment effect were explored (PROSPERO: CRD42021240485). RESULTS: Seventeen RCTs, synthesized across four meta-analyzes, indicated HEP depression outcomes were significantly better than TAU controls at post-treatment (g = 0.41, 95% CI [0.18, 0.65], n = 735), but not significantly different at follow-up (g = 0.14, 95% CI [-0.30, 0.58], n = 631). HEP depression outcomes were comparable to active treatments at post-treatment (g = -0.09, 95% CI [-0.26, 0.08], n = 2131), but significantly favored non-HEP alternative interventions at follow-up (g = -0.21, 95% CI [-0.35, -0.07], n = 1196). CONCLUSION: Relative to usual care, HEPs are effective in the short-term and comparable to non-HEP alternative interventions at post-treatment, but not at follow-up. However, imprecision, inconsistency, and risk of bias concerns were identified as limitations of the evidence included. Future large-scale trials of HEPs with equipoise between comparator conditions are required.

Early response as a prognostic indicator in person-centered experiential therapy for depression.

Currently, no reports exist on the phenomenon of early response in humanistic-experiential therapies. This study investigated the prognostic value of early response on posttreatment outcomes in person-centered experiential therapy (PCET) for depression within the English Improving Access to Psychological Therapies program. The design of the study was a retrospective observational cohort study. Routine clinical data were drawn from N = 3,321 patients with depression symptoms. The primary outcome was reliable and clinically significant improvement (RCSI) on the Patient Health Questionnaire-9 (PHQ-9) self-report depression measure at the end of treatment. Early response was operationalized as reliable improvement, defined as a PHQ-9 change score ≥ 6 from baseline to Session 4. Early response was examined as a predictor of RCSI using logistic regression controlling for baseline depression severity. In sensitivity analyses, therapist effects were controlled using multilevel modeling. A total of 38.7% of patients met the criterion for early response. Patients who experienced an early response to treatment were six times more likely to recover at the end of treatment compared to patients who did not have an early response. The early response effect was still evident after accounting for individual variability between therapists. However, a quarter of patients displayed a pattern of eventual response, reaching recovery at end of treatment despite not experiencing an initial improvement early in therapy. Early response to PCET is a reliable predictor of treatment outcome. Different response patterns evidenced in this study indicate that identifying subgroups of patients associated with early and eventual response could support clinical decision-making. (PsycInfo Database Record (c) 2022 APA, all rights reserved).