Might maintenance therapy be discontinued once clinical remission is achieved in ANCA-associated vasculitis?

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) encompasses a group of rare, multisystem autoimmune disorders characterised by the occurrence of inflammation and damage to small blood vessels, leading to a wide range of clinical manifestations. They include granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Outcomes for patients with MPA and GPA have been transformed over recent years. However, the establishment of effective maintenance therapy aiming to balance the risks of disease relapse with those related to prolonged immunosuppression has become a clinical priority. This review aims to explore two differing perspectives on this unsolved problem. Pros and Cons of the following approaches will be discussed: "Biomarker-guided personalised approach on top of generic maintenance strategy guidelines" or "ANCA specificity-related personalised maintenance treatment after intensive B-cell depletion"?

Evaluation of clinical factors and outcome of systemic glucocorticoid therapy discontinuation in patients with pemphigus achieving complete remission.

Therapy discontinuation of systemic glucocorticoid treatment for pemphigus remains uncertain at the clinical end point of complete remission. The objective of this study was to identify the factors associated with achieving complete remission off therapy (CROT) and analyze the occurrence of relapse after therapy discontinuation. A retrospective cohort study was conducted at the Department of Dermatology of Peking University First Hospital. A total of 447 patients with pemphigus treated from 2005 to 2020 were identified. Univariate and multivariate analyses were conducted to analyze the associated factors of CROT and to evaluate the outcomes. The mean age was 48 years (±13.4 years), and 54.6% of the patients were women. During a median follow-up of 59 months (43-87.5 months), 160 of 447 (35.8%) patients achieved CROT after a median treatment duration of 51 months (38-66.2 months). Patients with a shorter therapy duration to complete remission on minimal therapy and negative desmoglein antibodies tested in remission were more likely to achieve early CROT. Thirty-five of 160 (21.9%) patients experienced relapse after CROT. Patients who discontinued therapy without guidance experienced significantly faster and higher occurrences of relapse than those withdrawing under guidance (log-rank p = 0.01). Minimal therapy maintenance ≤8 months from complete remission on minimal therapy and positive desmoglein antibodies tested at withdrawal increased the risk of early relapse after CROT.

Sustained response off therapy after fostamatinib: A chronic refractory ITP case report.

Fostamatinib is a SYK-inhibitor drug recently approved by the FDA and EMA for treating chronic immune thrombocytopenia. This drug induces a response in about 40% of patients and has a good toxicity profile. It is known that discontinuing thrombopoietin receptor agonists (TRAs) with the maintenance of sustained response off therapy is possible. On fostamatinib, we do not yet have such information. In this case report, we describe the story of a woman with a multirefractory immune thrombocytopenia (steroids, splenectomy, rituximab, both available TRAs). After 16 years from diagnosis, she started fostamatinib therapy within a clinical trial and achieved a complete response. Grade 1-2 headache and diarrhea occurred during the first months of therapy. These adverse events were resolved with dose reduction of fostamatinib. Despite the dose reduction, the platelet count remained steadily above 80 × 109/L. After 4 years, fostamatinib was gradually reduced and finally discontinued with no drop in platelet count. This is the first case in which fostamatinib discontinuation resulted in a sustained response off therapy.

Differential Relapse Patterns After Discontinuation of Entecavir vs Tenofovir Disoproxil Fumarate in Chronic Hepatitis B.

BACKGROUND AND AIMS: Whether entecavir (ETV) and tenofovir disoproxil fumarate (TDF) differentially affect relapse and outcomes following treatment discontinuation across different patient subpopulations remains unclear. We aimed to compare rates of off-therapy hepatitis B surface antigen (HBsAg) loss, virological and clinical relapse, and retreatment between chronic hepatitis B (CHB) patients who discontinued TDF or ETV therapy. METHODS: This study included 1402 virally suppressed CHB patients who stopped either ETV (n = 981) or TDF (n = 421) therapy between 2001 and 2020 from 13 participating centers across North America, Europe, and Asia. All patients were hepatitis B e antigen-negative at treatment discontinuation. Inverse probability of treatment weighting was used to balance the treatment groups. Outcomes were analyzed using survival methods. RESULTS: During a median off-treatment follow-up of 18 months, HBsAg loss occurred in 96 (6.8%) patients overall. Compared with ETV, TDF was associated with a higher rate of HBsAg loss (P = .03); however, the association was no longer significant after statistical adjustment (P = .61). Virological relapse occurred earlier among TDF-treated patients (P < .01); nonetheless, rates became comparable after the first year off therapy (P = .49). TDF was significantly associated with a higher clinical relapse rate than ETV throughout follow-up (P < .01). The development of a virological or clinical relapse did not affect the rate of HBsAg loss. Retreatment rates were not significantly different between the treatment groups. CONCLUSIONS: TDF and ETV have differential relapse patterns but are associated with similar rates of HBsAg loss and retreatment following discontinuation. Finite therapy can be considered for CHB patients on either TDF or ETV therapy.

Major determinants of prolonged remission in systemic lupus erythematosus: retrospective study over a 41+ year period.

OBJECTIVES: To investigate predictors of sustained complete remission (CR) for 3 and 5 years, minimum. METHODS: Retrospective observational study from January 1978 to December 2019, including systemic lupus erythmatosus (SLE) patients who attended the Lupus Clinic in a tertiary hospital, for at least 3 years. We used the BILAG score and serological profile to classify patients into CR, serologically active clinically quiescent (SACQ) and serological remission (SR). Multivariable Cox regression analysis was performed to investigate predictors of CR and Kaplan-Meier curves were obtained. RESULTS: We included 564 patients; 15% achieved CR, 7% SACQ and 15% SR. Some 63% attained no remission. In the CR group, 73% sustained the remission for 5 years or more. Patients who did not reach any kind of sustained remission died significantly earlier (P < 0.001). Cumulative survival figures at 5, 10, 20 and 30 years were 100, 100, 94 and 90%, respectively, for CR patients and 96, 93, 77 and 58%, respectively, for patients in the no-remission group. Significant predictors of CR were White ethnicity [adjusted hazard ratio (HR) 2.16 (95% CI 1.30-3.59); P = 0.003]; older age at diagnosis (>32 years) [HR 1.92 (1.24-2.97); P = 0.003]; absence of renal involvement [HR 2.55 (1.39-4.67); P = 0.002]; and of antiphospholipid syndrome (APS) [HR 4.92 (1.55-15.59); P = 0.007]. CONCLUSION: Patients not achieving any kind of sustained remission have a higher risk of early mortality. White ethnicity, older age at diagnosis, absence of renal involvement and of APS were significantly associated with CR. Predictors for sustained CR do not change whether a 3-year or 5-year period is applied.

Characterization and prognostic implication of delayed complete response in AL amyloidosis.

INTRODUCTION: Little is known on continued response following completion of therapy in light chain (AL) amyloidosis. METHODS: We studied 373 AL amyloidosis patients who achieved complete response (CR) or very good partial response (VGPR) to first-line therapy. RESULTS: By end of therapy (EOT), 46% of patients achieved a CR and 54% a VGPR. With no further therapy, 17.5% of patients were upstaged from VGPR to CR (delayed CR), with a median of 9 months. Compared with CR and VGPR at EOT, patients with a delayed CR were characterized by higher proportion of t(11;14) and lower rate of trisomies. Autologous stem cell transplant was more frequent in the delayed CR group. Patients with a delayed CR were characterized by minimal residual disease negativity and organ response rates similar to patients with CR at EOT and higher than patients achieving VGPR at EOT. Patients with a delayed CR had a longer PFS/OS compared to patients with CR or VGPR by EOT (median PFS 149 vs 92 vs 52 months, P < .001; 10-year OS 87% vs 71% vs 56%, P < .001). CONCLUSIONS: This study characterizes delayed CR in AL amyloidosis, highlights its prognostic impact which is at least similar to those who achieved CR at EOT, and underlines another aspect of response monitoring.

Health and Psychosocial Self-Care Needs in Off-Therapy Childhood Cancer: Hybrid Model Concept Analysis.

PURPOSE: The self-care concept is a complicated and multi-dimensional phenomenon. There are different opinions about self-care needs; therefore, this study was conducted to clarify the self-care needs of the off-therapy childhood cancer survivors based on the hybrid model. PATIENTS AND METHODS: There are three phases in the hybrid model including literature review, fieldwork, and final analysis. At the theoretical phase, 119 articles in databases were evaluated without time limits up to August 2019. At the fieldwork phase, 19 participants were selected with purposive sampling and interviewed through unstructured interviews. Then, the data were analyzed by qualitative content analysis approach. In the final phase, the overall analysis of the two previous phases was carried out and the ultimate definition of self-care needs was presented with the integration of the results of two previous phases. RESULTS: Theoretical results showed that self-care needs are those that need to be performed by off therapy childhood cancer in everyday life in order to maintain health and well-being through the practice of healthy behaviors and activities. Also, fieldwork results indicated that self-care needs are increased due to the physical, mental, and social vulnerability of the disease. Following that, the need for protective self-care behaviors to prevent against physical and psychosocial side effects arises. If the patients are unable to implement protective behaviors, the need for support from others is created. Therefore, by synthesizing the findings of literature review and fieldwork, self-care needs are two-dimensional concept: (1) need for changing in behavior to protect themselves against physical and psychosocial distress and (2) need for supporting to implement care. CONCLUSION: Taking into account the self-care needs, healthcare providers can support childhood cancer survivors in gaining and maintaining independency in self-care. On the other hand, the results of this study by creating a basic knowledge in the field of self-care needs can be used in the development of policy and standards of care to meet the needs of this group.

Understanding Long-term Remission Off Therapy in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

INTRODUCTION: In antineutrophil cytoplasmic antibody-associated (ANCA) vasculitis, relapse risk and long-term immunosuppressive therapy are problematic. Stopping immunotherapy has not been well described. METHODS: The Glomerular Disease Collaborative Network ANCA vasculitis inception cohort was evaluated. Patients who stopped all immunotherapy and those continuously on immunotherapy (≥2 years) were included. Time to first period off therapy was modeled with end-stage kidney disease and death as competing risks to understand influences of stopping therapy. Cause-specific hazard ratios (HRs) with 95% confidence intervals (CI) and P values are reported. Models controlled for age, sex, ANCA specificity, organ involvement, diagnosis era, and treatments (yes/no). Repeated events analysis was used to assess the time-dependent variable of time off treatment on recurrent relapse with HRs, 95% CIs, and P values are reported (same control variables without treatments). RESULTS: In 427 patients, 277 (65%) stopped therapy (median 20 months from initial induction); 14% for ≥2 different periods of time and 23% for periods ≥5 years. In multivariable models of time to discontinuation of treatment, women (HR 1.33; 95% CI 1.04-1.70; P = 0.024) and those treated with pulse methylprednisolone (HR 1.39; 95% CI 1.05-1.84; P = 0.020) were more likely to stop. The time-dependent variable of time off treatment was associated with fewer recurrent relapses (HR 0.51; 95% CI 0.41-0.63; P < 0.001). CONCLUSIONS: Stopping immunotherapy was common. Women and those treated with methylprednisolone stop treatment more often, but underlying mechanisms are unknown. Stopping treatment was associated with fewer relapses, suggesting that even without guidelines there may be benefits without an untoward detriment of relapse.

INASL Position Statements on Prevention, Diagnosis and Management of Hepatitis B Virus Infection in India: The Andaman Statements.

Hepatitis B Virus (HBV) infection is one of the major causes of morbidity, mortality and healthcare expenditure in India. There are no Indian consensus guidelines on prevention, diagnosis and management of HBV infection. The Indian National Association for Study of the Liver (INASL) set up a taskforce on HBV in 2016, with a mandate to develop consensus guidelines for diagnosis and management of HBV infection, relevant to disease patterns and clinical practices in India. The taskforce first identified contentious issues on various aspects of HBV management, which were allotted to individual members of the taskforce who reviewed them in detail. A 2-day round table discussion was held on 11th and 12th February 2017 at Port Blair, Andaman & Nicobar Islands, to discuss, debate, and finalize the consensus statements. The members of the taskforce reviewed and discussed the existing literature threadbare at this meeting and formulated the 'INASL position statements' on each of the issues. The evidence and recommendations in these guidelines have been graded according to the Grading of Recommendations Assessment Development and Evaluation (GRADE) system with minor modifications. The strength of recommendations (strong: 1, weak: 2) thus reflects the quality (grade) of underlying evidence (A, B, C, D). We present here the INASL position statements on prevention, diagnosis and management of HBV in India.

Serum viral load at the virological relapse predicts subsequent clinical flares in chronic hepatitis B patients off entecavir therapy.

BACKGROUND AND AIM: Therapeutic duration of nucleos(t)ide analogues for chronic hepatitis B (CHB) is not indefinite in many parts of the world. Viral reactivation is common off therapy, but the risk of subsequent clinical outcome remains unclear and unpredictable. We aimed to quantify the incidence of and explore the predictors for clinical flare following virological relapse in CHB patients who discontinue entecavir therapy. METHODS: This multicenter cohort study prospectively monitored 133 CHB patients who were HBeAg-negative and viral DNA-undetectable when discontinuing entecavir after at least 3 years on therapy. Following virological relapse (viral DNA >2,000 IU/mL) that occurred in 92 patients, the incidences of subsequent clinical flare and persistent (unremittent for 3 months) or severe hepatitis (with jaundice or coagulopathy) were determined, and risk factors were explored. Patients did not resume antiviral therapy until occurrence of persistent or severe hepatitis. RESULTS: The cumulative incidence of clinical hepatitis 2 years after virological relapse was 61.0% (95% confidence interval [CI], 49.9-72.3%) and that of persistent or severe hepatitis was 53.0% (95% CI, 40.9-66.2%). Serum viral load at the virological relapse was associated with both clinical hepatitis (adjusted hazard ratio [HR], 1.31 per log IU/mL; 95% CI, 1.07-1.60) and persistent or severe hepatitis (adjusted HR, 1.63 per log IU/mL; 95% CI, 1.27-2.10), after adjustment for serum aminotransferase and alfa-fetoprotein levels in the multivariate analysis. Viral DNA >100 000 IU/mL predicted a nearly inevitable occurrence of clinical flare (P < 0.0001). CONCLUSIONS: A high viral load at the virological relapse predicts subsequent clinical hepatitis in CHB patients who discontinue entecavir.

Off-therapy procedures are not beneficial in pediatric B-cell acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Although curable, approximately 20% of patients relapse. In an effort to detect relapse earlier, our institution performed surveillance bone marrow (BM) and cerebrospinal fluid (CSF) evaluations every 3 months from the end of therapy to 1 year off. This study retrospectively reviewed all patients with B-cell ALL (B-ALL) from September 2005 to September 2010 to determine the benefit and cost of these procedures. Forty-one patients completed therapy and had 190 BMs and 190 lumbar punctures (LPs) performed. Four of 41 patients (9.8%) experienced a relapse. Relapse was detected in only 1 patient by routine BM evaluation (0.5%). Zero LPs were positive. The professional fees for the procedures were $8,738/patient. Therefore, off-therapy BM and CSF evaluations are not effective at detecting relapse and are expensive. Our institution has abandoned off-therapy surveillance for ALL.

Assessment of the rate of long-term complete remission off therapy in patients with pemphigus treated with different regimens including medium- and high-dose corticosteroids.

BACKGROUND: Few studies have evaluated pemphigus treatments according to the definitions of the consensus statement. Prognostic factors for complete remission off therapy (CRoffT) remain unknown. OBJECTIVE: We sought to assess the rate of CRoffT in patients with pemphigus treated with different regimens. METHODS: In all, 134 patients with pemphigus were included in a retrospective, multicenter study. Primary end point was the rate of CRoffT. Prognostic factors for CRoffT were determined using univariate and multivariate analyses. RESULTS: Eighty patients with pemphigus vulgaris, 47 with pemphigus foliaceus, and 7 with paraneoplastic pemphigus were included. Mean age was 60 ± 18 years. Patients were treated either with medium (≤0.5 mg/kg/d) (n = 32) or high (≥1 mg/kg/d) (n = 59) doses of prednisone, or without systemic corticosteroids (n = 43). Mean follow-up was 77 ± 64 months. In all, 68 patients (50.7%) achieved CRoffT (95% confidence interval 42.3%-59.2%) after a mean treatment duration of 36 ± 39 months, including 47 of 80 patients with pemphigus vulgaris (58.7%) and 21 of 47 with pemphigus foliaceus (44.7%). Main prognostic factors for CRoffT were initial mucosal involvement (hazard ratio 2.2; 95% confidence interval 1.05-4.58; P = .036) and younger age (<61 years) (hazard ratio 2.5; 95% confidence interval 1.18-5.12; P = .0167). The rate of long-lasting CRoffT was 44%, with a mean follow-up after treatment withdrawal of 59 ± 50 months. LIMITATIONS: This was a retrospective study. CONCLUSION: The rate of CRoffT was 51%. Patients with pemphigus vulgaris were more likely to achieve CRoffT than those with pemphigus foliaceus.