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Katie Macarthur - One of the best experts on this subject based on the ideXlab platform.

  • spontaneous and Tetracosactide induced anti acth antibodies in man
    Clinical Endocrinology, 2016
    Co-Authors: Katie Macarthur, Anna L. Mitchell, Abhijit Joshi, Patricia Crock, Simon H. S. Pearce
    Abstract:

    SummaryContext During a clinical trial of regular Tetracosactide depot injections, four of 13 patients with autoimmune Addison's disease (AAD) developed adverse reactions immediately following Tetracosactide injections. We wished to investigate whether these adverse effects could be due to the production of circulating antiTetracosactide (ACTH1–24) antibodies. Design Anti-ACTH binding activity was investigated using immunoblotting and ELISA on sera from participants in the trial (n = 13; baseline and after Tetracosactide exposure), 131 unrelated patients with AAD, 92 patients with Graves’ disease (GD), 15 patients with isolated ACTH deficiency and 102 controls. Immunohistochemistry of human pituitary tissue sections was also performed using pooled sera. Results Bands at approximately 4 and 6 kDa, corresponding to ACTH1–24 and full-length ACTH1–39, respectively, were found in 10 of 13 (77%) of sera from trial patients exposed to Tetracosactide, including all those who had an adverse reaction. This is in contrast with healthy control sera, which showed no binding. The same 10 subjects also showed high levels of binding to Tetracosactide by ELISA, along with 21% of patients with AAD, 14% of patients with GD (both P < 0·001 compared to controls) and 1 isolated ACTH deficiency patient (7% of 15). These sera also recognized native ACTH in human pituitary sections. Conclusion Our study demonstrates that repeated administration of depot Tetracosactide can lead to anti-ACTH1–24 autoreactivity. In addition, a significant number of patients with AAD and GD also had similar, spontaneous, anti-ACTH reactivity. The presence of these antibodies could mediate some of the adverse effects or explain the well-described phenomenon of resistance to chronic ACTH therapy.

  • Spontaneous and Tetracosactide-induced anti-ACTH antibodies in man
    Clinical Endocrinology, 2015
    Co-Authors: Katie Macarthur, Anna L. Mitchell, Abhijit Joshi, Patricia Crock, Simon H. S. Pearce
    Abstract:

    SummaryContext During a clinical trial of regular Tetracosactide depot injections, four of 13 patients with autoimmune Addison's disease (AAD) developed adverse reactions immediately following Tetracosactide injections. We wished to investigate whether these adverse effects could be due to the production of circulating antiTetracosactide (ACTH1–24) antibodies. Design Anti-ACTH binding activity was investigated using immunoblotting and ELISA on sera from participants in the trial (n = 13; baseline and after Tetracosactide exposure), 131 unrelated patients with AAD, 92 patients with Graves’ disease (GD), 15 patients with isolated ACTH deficiency and 102 controls. Immunohistochemistry of human pituitary tissue sections was also performed using pooled sera. Results Bands at approximately 4 and 6 kDa, corresponding to ACTH1–24 and full-length ACTH1–39, respectively, were found in 10 of 13 (77%) of sera from trial patients exposed to Tetracosactide, including all those who had an adverse reaction. This is in contrast with healthy control sera, which showed no binding. The same 10 subjects also showed high levels of binding to Tetracosactide by ELISA, along with 21% of patients with AAD, 14% of patients with GD (both P 

  • residual adrenal function in autoimmune addison s disease improvement after Tetracosactide acth1 24 treatment
    The Journal of Clinical Endocrinology and Metabolism, 2014
    Co-Authors: Katie Macarthur, Anna L. Mitchell, Beverly A Hughes, Petros Perros, Stephen G Ball, Andrew R James, Richard Quinton
    Abstract:

    Context: Despite lifelong steroid hormone replacement, there is excess morbidity and mortality associated with autoimmune Addison's disease. In health, adrenocortical cells undergo continuous self-renewal from a population of subcapsular progenitor cells, under the influence of ACTH, suggesting a therapeutic possibility. Objective: We aimed to determine whether Tetracosactide (synthetic ACTH1–24) could revive adrenal steroidogenic function in autoimmune Addison's disease. Design, Setting, and Patients: Thirteen patients (aged 16–65 y) with established autoimmune Addison's disease for more than 1 year were recruited at the Newcastle University Clinical Research Facility. Intervention: The intervention included a 20-week study of regular sc Tetracosactide (ACTH1–24) therapy. Main Outcome Measures: Serum and urine corticosteroids were measured during medication withdrawal at baseline and every 5 weeks during the study. Results: Serum cortisol levels remained less than 100 nmol/L in 11 of 13 participants thro...

  • Residual Adrenal Function in Autoimmune Addison's Disease: Improvement After Tetracosactide (ACTH1–24) Treatment
    The Journal of Clinical Endocrinology and Metabolism, 2013
    Co-Authors: Katie Macarthur, Anna L. Mitchell, Beverly A Hughes, Petros Perros, Stephen G Ball, Richard Quinton, R. Andrew James, Shu Chen, Jadwiga Furmaniak
    Abstract:

    Context: Despite lifelong steroid hormone replacement, there is excess morbidity and mortality associated with autoimmune Addison's disease. In health, adrenocortical cells undergo continuous self-renewal from a population of subcapsular progenitor cells, under the influence of ACTH, suggesting a therapeutic possibility. Objective: We aimed to determine whether Tetracosactide (synthetic ACTH1–24) could revive adrenal steroidogenic function in autoimmune Addison's disease. Design, Setting, and Patients: Thirteen patients (aged 16–65 y) with established autoimmune Addison's disease for more than 1 year were recruited at the Newcastle University Clinical Research Facility. Intervention: The intervention included a 20-week study of regular sc Tetracosactide (ACTH1–24) therapy. Main Outcome Measures: Serum and urine corticosteroids were measured during medication withdrawal at baseline and every 5 weeks during the study. Results: Serum cortisol levels remained less than 100 nmol/L in 11 of 13 participants thro...

Anna L. Mitchell - One of the best experts on this subject based on the ideXlab platform.

  • residual adrenal function in autoimmune addison s disease effect of dual therapy with rituximab and depot Tetracosactide
    The Journal of Clinical Endocrinology and Metabolism, 2020
    Co-Authors: Catherine Napier, Anna L. Mitchell, Andrew R James, Lorna C Gilligan, Aled D Rees, Carla Moran, Krishna Chatterjee, Bijay Vaidya, Yaasir Mamoojee, Simon Ashwell
    Abstract:

    Context In autoimmune Addison’s disease (AAD), exogenous glucocorticoid (GC) therapy is an imperfect substitute for physiological GC secretion. Patients on long-term steroid replacement have increased morbidity, reduced life expectancy and poorer quality of life. Objective To restore adrenocortical steroidogenic function in recent onset AAD. Design Open-label, multi-centre trial of immunotherapy and trophic stimulation in new-onset AAD. Serial measurement of serum and urine corticosteroids at baseline and throughout 72-week follow-up period. Setting Endocrine Departments and Clinical Research Facilities at 5 UK tertiary centres. Patients Thirteen subjects (9 female, 4 male; aged 19-64 years) with AAD confirmed by high ACTH, low circulating cortisol (basal <100nmol/L or post-Tetracosactide <300nmol/L) and positive serum 21-hydroxylase antibodies. Intervention All subjects received dual therapy with B-lymphocyte depleting immunotherapy (rituximab 1g given twice) and repeated depot Tetracosactide (1mg alternate days for 12 weeks). Main Outcome Measure Restoration of normal glucocorticoid secretion (stimulated cortisol >550nmol/L) at Week 48. Results Ten of 13 (77%) had detectable stimulated serum cortisol (26-265nmol/L) at trial entry. Following intervention, 7/13 (54%) had an increase in stimulated cortisol measurement, with a peak response of 325nmol/L at Week 18 in one subject. Increased steroid metabolites, assayed by urine GC-MS at Week 12 and Week 48, was detected in 8/13 (62%), reflecting an increase in endogenous steroidogenesis. Four of 13 had Residual Adrenal Function at 72 weeks. Conclusion Combined treatment with rituximab and depot Tetracosactide did not restore normal adrenal function. Nevertheless, adrenocortical plasticity is demonstrated in some patients and this has the potential to be exploited to improve adrenal function.

  • spontaneous and Tetracosactide induced anti acth antibodies in man
    Clinical Endocrinology, 2016
    Co-Authors: Katie Macarthur, Anna L. Mitchell, Abhijit Joshi, Patricia Crock, Simon H. S. Pearce
    Abstract:

    SummaryContext During a clinical trial of regular Tetracosactide depot injections, four of 13 patients with autoimmune Addison's disease (AAD) developed adverse reactions immediately following Tetracosactide injections. We wished to investigate whether these adverse effects could be due to the production of circulating antiTetracosactide (ACTH1–24) antibodies. Design Anti-ACTH binding activity was investigated using immunoblotting and ELISA on sera from participants in the trial (n = 13; baseline and after Tetracosactide exposure), 131 unrelated patients with AAD, 92 patients with Graves’ disease (GD), 15 patients with isolated ACTH deficiency and 102 controls. Immunohistochemistry of human pituitary tissue sections was also performed using pooled sera. Results Bands at approximately 4 and 6 kDa, corresponding to ACTH1–24 and full-length ACTH1–39, respectively, were found in 10 of 13 (77%) of sera from trial patients exposed to Tetracosactide, including all those who had an adverse reaction. This is in contrast with healthy control sera, which showed no binding. The same 10 subjects also showed high levels of binding to Tetracosactide by ELISA, along with 21% of patients with AAD, 14% of patients with GD (both P < 0·001 compared to controls) and 1 isolated ACTH deficiency patient (7% of 15). These sera also recognized native ACTH in human pituitary sections. Conclusion Our study demonstrates that repeated administration of depot Tetracosactide can lead to anti-ACTH1–24 autoreactivity. In addition, a significant number of patients with AAD and GD also had similar, spontaneous, anti-ACTH reactivity. The presence of these antibodies could mediate some of the adverse effects or explain the well-described phenomenon of resistance to chronic ACTH therapy.

  • Spontaneous and Tetracosactide-induced anti-ACTH antibodies in man
    Clinical Endocrinology, 2015
    Co-Authors: Katie Macarthur, Anna L. Mitchell, Abhijit Joshi, Patricia Crock, Simon H. S. Pearce
    Abstract:

    SummaryContext During a clinical trial of regular Tetracosactide depot injections, four of 13 patients with autoimmune Addison's disease (AAD) developed adverse reactions immediately following Tetracosactide injections. We wished to investigate whether these adverse effects could be due to the production of circulating antiTetracosactide (ACTH1–24) antibodies. Design Anti-ACTH binding activity was investigated using immunoblotting and ELISA on sera from participants in the trial (n = 13; baseline and after Tetracosactide exposure), 131 unrelated patients with AAD, 92 patients with Graves’ disease (GD), 15 patients with isolated ACTH deficiency and 102 controls. Immunohistochemistry of human pituitary tissue sections was also performed using pooled sera. Results Bands at approximately 4 and 6 kDa, corresponding to ACTH1–24 and full-length ACTH1–39, respectively, were found in 10 of 13 (77%) of sera from trial patients exposed to Tetracosactide, including all those who had an adverse reaction. This is in contrast with healthy control sera, which showed no binding. The same 10 subjects also showed high levels of binding to Tetracosactide by ELISA, along with 21% of patients with AAD, 14% of patients with GD (both P 

  • residual adrenal function in autoimmune addison s disease improvement after Tetracosactide acth1 24 treatment
    The Journal of Clinical Endocrinology and Metabolism, 2014
    Co-Authors: Katie Macarthur, Anna L. Mitchell, Beverly A Hughes, Petros Perros, Stephen G Ball, Andrew R James, Richard Quinton
    Abstract:

    Context: Despite lifelong steroid hormone replacement, there is excess morbidity and mortality associated with autoimmune Addison's disease. In health, adrenocortical cells undergo continuous self-renewal from a population of subcapsular progenitor cells, under the influence of ACTH, suggesting a therapeutic possibility. Objective: We aimed to determine whether Tetracosactide (synthetic ACTH1–24) could revive adrenal steroidogenic function in autoimmune Addison's disease. Design, Setting, and Patients: Thirteen patients (aged 16–65 y) with established autoimmune Addison's disease for more than 1 year were recruited at the Newcastle University Clinical Research Facility. Intervention: The intervention included a 20-week study of regular sc Tetracosactide (ACTH1–24) therapy. Main Outcome Measures: Serum and urine corticosteroids were measured during medication withdrawal at baseline and every 5 weeks during the study. Results: Serum cortisol levels remained less than 100 nmol/L in 11 of 13 participants thro...

  • Residual Adrenal Function in Autoimmune Addison's Disease: Improvement After Tetracosactide (ACTH1–24) Treatment
    The Journal of Clinical Endocrinology and Metabolism, 2013
    Co-Authors: Katie Macarthur, Anna L. Mitchell, Beverly A Hughes, Petros Perros, Stephen G Ball, Richard Quinton, R. Andrew James, Shu Chen, Jadwiga Furmaniak
    Abstract:

    Context: Despite lifelong steroid hormone replacement, there is excess morbidity and mortality associated with autoimmune Addison's disease. In health, adrenocortical cells undergo continuous self-renewal from a population of subcapsular progenitor cells, under the influence of ACTH, suggesting a therapeutic possibility. Objective: We aimed to determine whether Tetracosactide (synthetic ACTH1–24) could revive adrenal steroidogenic function in autoimmune Addison's disease. Design, Setting, and Patients: Thirteen patients (aged 16–65 y) with established autoimmune Addison's disease for more than 1 year were recruited at the Newcastle University Clinical Research Facility. Intervention: The intervention included a 20-week study of regular sc Tetracosactide (ACTH1–24) therapy. Main Outcome Measures: Serum and urine corticosteroids were measured during medication withdrawal at baseline and every 5 weeks during the study. Results: Serum cortisol levels remained less than 100 nmol/L in 11 of 13 participants thro...

Finbar Ocallaghan - One of the best experts on this subject based on the ideXlab platform.

  • op51 3033 prednisolone or Tetracosactide depot for infantile spasms a meta analysis from ukiss and iciss
    European Journal of Paediatric Neurology, 2015
    Co-Authors: John P Osborne, Eleanor Hancock, Stuart W Edwards, Finbar Ocallaghan
    Abstract:

    Objective To examine the relative efficacy of prednisolone and Tetracosactide depot in the treatment of infantile spasms using data from trials where treatment had been randomly allocated. Prednisone trials (against ACTH) were not included since prednisone is an inactive compound that infants poorly convert to the active compound, Prednisolone. Methods A meta-analysis of results from both UKISS and ICISS clinical trials. Both trials compared hormonal treatment alone (either Prednisolone or Tetracosactide Depot) to another treatment regime but had randomly allocated the hormonal treatment in all (UKISS) or some (ICISS) infants. Both trials used the same dosages: Prednisolone 10 mg qds increasing to 20 mg tds after 7 days if spasms continued or Tetracosactide depot 0.5 mg on alternate days increasing to 0.75 mg after 7 days if spasms continued. Cessation of spasms was defined as in UKISS: no visible spasms on Days 13 and 14. This outcome was also available for infants in ICISS where a more stringent definition was used. Results 124 infants (53 in UKISS and 71 in ICISS) were randomly allocated either Prednisolone (64) or Tetracosactide depot (60). Results for all infants are available. Cessation of spasms was achieved in 43 (67%) of those allocated Prednisolone and in 45 (75%) of those allocated Tetracosactide depot. There is no significant difference between these outcomes (Treatment difference 7.8%, 95% CI: –8.7% to +24.3%; Chi-square 0.92 and p=0.34). Conclusion When these two treatments are used as initial single treatments and where cessation of spasms is the outcome measure, there is no evidence that one treatment is better than the other.

  • op50 3017 the international collaborative infantile spasms study iciss comparing hormonal therapies prednisolone or Tetracosactide depot and vigabatrin versus hormonal therapies alone in the treatment of infantile spasms early clinical outcome
    European Journal of Paediatric Neurology, 2015
    Co-Authors: Finbar Ocallaghan, A L Johnson, Colin R Kennedy, S Edwards, E Hancock, Mark T Mackay, R Newton, Melinda Nolan, D Rating, B Schmitt
    Abstract:

    Objective To compare hormonal therapies (Prednisolone or Tetracosactide depot) and vigabatrin versus hormonal therapies alone in the treatment of infantile spasms. Methods Between March 2007 and May 2014, infants with IS and a compatible EEG were enrolled in a multicenter treatment trial. Infants were randomized to receive either hormonal therapy and vigabatrin or hormonal therapy alone. A second stage randomization allowed hormonal treatment to be allocated as either prednisolone or Tetracosactide depot. Minimum doses were: vigabatrin 100 mg/kg/day, prednisolone 40 mg per day, or IM Tetracosactide depot 0.5 mg on alternate days. The early primary outcome measure was cessation of spasms on and between days 14 and 42. Analysis is by intention to treat. Results 377 children were enrolled and early clinical outcome data will be available on 376 (1 case withdrew). 185 were allocated hormonal therapy and vigabatrin and 191 were allocated hormonal therapy alone. 133/185 (71.9%) on combination therapy versus 108/191 (56.6%) on hormonal therapy alone achieved a primary clinical response: treatment difference 15.3% (95% CI 5.4% to 25.2%, p=0.002). The treatment effect favouring combination therapy remained highly significant in a logistic regression analysis controlling for underlying aetiology, country of enrollment, whether hormonal therapy was randomized or not, and gender (Odds ratio 2.03, 95% CI 1.3 to 3.2, p=0.002). Treatment response was also significantly faster on combination therapy (median response time = 2 days, IQR 2–4 days) than hormonal therapy alone (median response time = 4 days, IQR 3–6 days, p Conclusion The ICISS trial shows that combination therapy of hormonal therapy + vigabatrin is associated with a more rapid clinical response and greater proportion of infants achieving spasm cessation than on hormonal therapy alone.

  • the united kingdom infantile spasms study comparing vigabatrin with prednisolone or Tetracosactide at 14 days a multicentre randomised controlled trial
    The Lancet, 2004
    Co-Authors: Stuart W Edwards, Eleanor Hancock, Finbar Ocallaghan, A L Johnson, Colin R Kennedy, Richard W Newton, Christiopher M Verity, John P Osborne
    Abstract:

    Summary Background Infantile spasms, which comprise a severe infantile seizure disorder, have a high morbidity and are difficult to treat. Hormonal treatments (adrenocorticotropic hormone and prednisolone) have been the main therapy for decades, although little evidence supports their use. Vigabatrin has been recorded to have a beneficial effect in this disorder. We aimed to compare the effects of vigabatrin with those of prednisolone and Tetracosactide in the treatment of infantile spasms. Methods The United Kingdom Infantile Spasms Study assessed these treatments in a multicentre, randomised controlled trial in 150 hospitals in the UK. The primary outcome was cessation of spasms on days 13 and 14. Minimum doses were vigabatrin 100 mg/kg per day, oral prednisolone 40 mg per day, or intramuscular Tetracosactide depot 0·5 mg (40 IU) on alternate days. Analysis was by intention to treat. Findings Of 208 infants screened and assessed, 107 were randomly assigned to vigabatrin (n=52) or hormonal treatments (prednisolone n=30, Tetracosactide n=25). None was lost to follow-up. Proportions with no spasms on days 13 and 14 were: 40 (73%) of 55 infants assigned hormonal treatments (prednisolone 21/30 [70%], Tetracosactide 19/25 [76%]) and 28 (54%) of 52 infants assigned vigabatrin (difference 19%, 95% CI 1%–36%, p=0·043). Two infants allocated Tetracosactide and one allocated vigabatrin received prednisolone. Adverse events were reported in 30 (55%) of 55 infants on hormonal treatments and 28 (54%) of 52 infants on vigabatrin. No deaths were recorded. Interpretation Cessation of spasms was more likely in infants given hormonal treatments than those given vigabatrin. Adverse events were common with both treatments.

Stuart W Edwards - One of the best experts on this subject based on the ideXlab platform.

  • op51 3033 prednisolone or Tetracosactide depot for infantile spasms a meta analysis from ukiss and iciss
    European Journal of Paediatric Neurology, 2015
    Co-Authors: John P Osborne, Eleanor Hancock, Stuart W Edwards, Finbar Ocallaghan
    Abstract:

    Objective To examine the relative efficacy of prednisolone and Tetracosactide depot in the treatment of infantile spasms using data from trials where treatment had been randomly allocated. Prednisone trials (against ACTH) were not included since prednisone is an inactive compound that infants poorly convert to the active compound, Prednisolone. Methods A meta-analysis of results from both UKISS and ICISS clinical trials. Both trials compared hormonal treatment alone (either Prednisolone or Tetracosactide Depot) to another treatment regime but had randomly allocated the hormonal treatment in all (UKISS) or some (ICISS) infants. Both trials used the same dosages: Prednisolone 10 mg qds increasing to 20 mg tds after 7 days if spasms continued or Tetracosactide depot 0.5 mg on alternate days increasing to 0.75 mg after 7 days if spasms continued. Cessation of spasms was defined as in UKISS: no visible spasms on Days 13 and 14. This outcome was also available for infants in ICISS where a more stringent definition was used. Results 124 infants (53 in UKISS and 71 in ICISS) were randomly allocated either Prednisolone (64) or Tetracosactide depot (60). Results for all infants are available. Cessation of spasms was achieved in 43 (67%) of those allocated Prednisolone and in 45 (75%) of those allocated Tetracosactide depot. There is no significant difference between these outcomes (Treatment difference 7.8%, 95% CI: –8.7% to +24.3%; Chi-square 0.92 and p=0.34). Conclusion When these two treatments are used as initial single treatments and where cessation of spasms is the outcome measure, there is no evidence that one treatment is better than the other.

  • OP51 – 3033: Prednisolone or Tetracosactide depot for infantile spasms – A meta-analysis from UKISS and ICISS
    European Journal of Paediatric Neurology, 2015
    Co-Authors: John P Osborne, Eleanor Hancock, Stuart W Edwards, Finbar O'callaghan
    Abstract:

    Objective To examine the relative efficacy of prednisolone and Tetracosactide depot in the treatment of infantile spasms using data from trials where treatment had been randomly allocated. Prednisone trials (against ACTH) were not included since prednisone is an inactive compound that infants poorly convert to the active compound, Prednisolone. Methods A meta-analysis of results from both UKISS and ICISS clinical trials. Both trials compared hormonal treatment alone (either Prednisolone or Tetracosactide Depot) to another treatment regime but had randomly allocated the hormonal treatment in all (UKISS) or some (ICISS) infants. Both trials used the same dosages: Prednisolone 10 mg qds increasing to 20 mg tds after 7 days if spasms continued or Tetracosactide depot 0.5 mg on alternate days increasing to 0.75 mg after 7 days if spasms continued. Cessation of spasms was defined as in UKISS: no visible spasms on Days 13 and 14. This outcome was also available for infants in ICISS where a more stringent definition was used. Results 124 infants (53 in UKISS and 71 in ICISS) were randomly allocated either Prednisolone (64) or Tetracosactide depot (60). Results for all infants are available. Cessation of spasms was achieved in 43 (67%) of those allocated Prednisolone and in 45 (75%) of those allocated Tetracosactide depot. There is no significant difference between these outcomes (Treatment difference 7.8%, 95% CI: –8.7% to +24.3%; Chi-square 0.92 and p=0.34). Conclusion When these two treatments are used as initial single treatments and where cessation of spasms is the outcome measure, there is no evidence that one treatment is better than the other.

  • g59 the international collaborative infantile spasms study iciss comparing hormonal therapies prednisolone or Tetracosactide depot and vigabatrin versus hormonal therapies alone in the treatment of infantile spasms early clinical outcome
    Archives of Disease in Childhood, 2015
    Co-Authors: F Ocallaghan, Eleanor Hancock, Stuart W Edwards, A L Johnson, Colin R Kennedy, Richard W Newton, Mark T Mackay, Melinda Nolan, D Rating
    Abstract:

    Infantile spasms (IS) are a serious epileptic encephalopathy that occur most commonly between 2 and 14 months. The spasms occur in association with hypsarrhythmia or similar on EEG. There is often coincident psychomotor arrest or regression. Between March 2007 and May 2014, infants with IS and a compatible EEG were enrolled in a multicenter treatment trial. Participating countries were the UK, Germany, Switzerland, Australia and New Zealand. Infants were randomised to receive either hormonal therapy and vigabatrin or hormonal therapy alone. A second stage randomization allowed hormonal treatment to be allocated as either prednisolone or Tetracosactide depot. Minimum doses were: vigabatrin 100 mg/kg/day, prednisolone 40 mg per day, or IM Tetracosactide depot 0.5 mg on alternate days. Hormonal treatment was continued for 2 weeks and then weaned over 2 weeks. Vigabatrin was continued for 3 months and then weaned over a month. The early primary outcome measure was cessation of spasms on and between days 14 and 42. Analysis is by intention to treat. 377 children were enrolled and early clinical outcome data will be available on 376 (1 case withdrew). 186 were allocated hormonal therapy and vigabatrin and 191 were allocated hormonal therapy alone. We will report on the primary clinical outcome and serious adverse clinical events. Developmental outcome at 18 months of age will be reported in a subsequent paper. To date this is by far the largest treatment study of infantile spasms ever undertaken.

  • the united kingdom infantile spasms study comparing vigabatrin with prednisolone or Tetracosactide at 14 days a multicentre randomised controlled trial
    The Lancet, 2004
    Co-Authors: Stuart W Edwards, Eleanor Hancock, Finbar Ocallaghan, A L Johnson, Colin R Kennedy, Richard W Newton, Christiopher M Verity, John P Osborne
    Abstract:

    Summary Background Infantile spasms, which comprise a severe infantile seizure disorder, have a high morbidity and are difficult to treat. Hormonal treatments (adrenocorticotropic hormone and prednisolone) have been the main therapy for decades, although little evidence supports their use. Vigabatrin has been recorded to have a beneficial effect in this disorder. We aimed to compare the effects of vigabatrin with those of prednisolone and Tetracosactide in the treatment of infantile spasms. Methods The United Kingdom Infantile Spasms Study assessed these treatments in a multicentre, randomised controlled trial in 150 hospitals in the UK. The primary outcome was cessation of spasms on days 13 and 14. Minimum doses were vigabatrin 100 mg/kg per day, oral prednisolone 40 mg per day, or intramuscular Tetracosactide depot 0·5 mg (40 IU) on alternate days. Analysis was by intention to treat. Findings Of 208 infants screened and assessed, 107 were randomly assigned to vigabatrin (n=52) or hormonal treatments (prednisolone n=30, Tetracosactide n=25). None was lost to follow-up. Proportions with no spasms on days 13 and 14 were: 40 (73%) of 55 infants assigned hormonal treatments (prednisolone 21/30 [70%], Tetracosactide 19/25 [76%]) and 28 (54%) of 52 infants assigned vigabatrin (difference 19%, 95% CI 1%–36%, p=0·043). Two infants allocated Tetracosactide and one allocated vigabatrin received prednisolone. Adverse events were reported in 30 (55%) of 55 infants on hormonal treatments and 28 (54%) of 52 infants on vigabatrin. No deaths were recorded. Interpretation Cessation of spasms was more likely in infants given hormonal treatments than those given vigabatrin. Adverse events were common with both treatments.

Simon H. S. Pearce - One of the best experts on this subject based on the ideXlab platform.

  • spontaneous and Tetracosactide induced anti acth antibodies in man
    Clinical Endocrinology, 2016
    Co-Authors: Katie Macarthur, Anna L. Mitchell, Abhijit Joshi, Patricia Crock, Simon H. S. Pearce
    Abstract:

    SummaryContext During a clinical trial of regular Tetracosactide depot injections, four of 13 patients with autoimmune Addison's disease (AAD) developed adverse reactions immediately following Tetracosactide injections. We wished to investigate whether these adverse effects could be due to the production of circulating antiTetracosactide (ACTH1–24) antibodies. Design Anti-ACTH binding activity was investigated using immunoblotting and ELISA on sera from participants in the trial (n = 13; baseline and after Tetracosactide exposure), 131 unrelated patients with AAD, 92 patients with Graves’ disease (GD), 15 patients with isolated ACTH deficiency and 102 controls. Immunohistochemistry of human pituitary tissue sections was also performed using pooled sera. Results Bands at approximately 4 and 6 kDa, corresponding to ACTH1–24 and full-length ACTH1–39, respectively, were found in 10 of 13 (77%) of sera from trial patients exposed to Tetracosactide, including all those who had an adverse reaction. This is in contrast with healthy control sera, which showed no binding. The same 10 subjects also showed high levels of binding to Tetracosactide by ELISA, along with 21% of patients with AAD, 14% of patients with GD (both P < 0·001 compared to controls) and 1 isolated ACTH deficiency patient (7% of 15). These sera also recognized native ACTH in human pituitary sections. Conclusion Our study demonstrates that repeated administration of depot Tetracosactide can lead to anti-ACTH1–24 autoreactivity. In addition, a significant number of patients with AAD and GD also had similar, spontaneous, anti-ACTH reactivity. The presence of these antibodies could mediate some of the adverse effects or explain the well-described phenomenon of resistance to chronic ACTH therapy.

  • Spontaneous and Tetracosactide-induced anti-ACTH antibodies in man
    Clinical Endocrinology, 2015
    Co-Authors: Katie Macarthur, Anna L. Mitchell, Abhijit Joshi, Patricia Crock, Simon H. S. Pearce
    Abstract:

    SummaryContext During a clinical trial of regular Tetracosactide depot injections, four of 13 patients with autoimmune Addison's disease (AAD) developed adverse reactions immediately following Tetracosactide injections. We wished to investigate whether these adverse effects could be due to the production of circulating antiTetracosactide (ACTH1–24) antibodies. Design Anti-ACTH binding activity was investigated using immunoblotting and ELISA on sera from participants in the trial (n = 13; baseline and after Tetracosactide exposure), 131 unrelated patients with AAD, 92 patients with Graves’ disease (GD), 15 patients with isolated ACTH deficiency and 102 controls. Immunohistochemistry of human pituitary tissue sections was also performed using pooled sera. Results Bands at approximately 4 and 6 kDa, corresponding to ACTH1–24 and full-length ACTH1–39, respectively, were found in 10 of 13 (77%) of sera from trial patients exposed to Tetracosactide, including all those who had an adverse reaction. This is in contrast with healthy control sera, which showed no binding. The same 10 subjects also showed high levels of binding to Tetracosactide by ELISA, along with 21% of patients with AAD, 14% of patients with GD (both P