Negative clinical trials in sarcoidosis: failed therapies or flawed study design?

Möller, David R.

doi:10.1183/09031936.00156314

Cited by 31 publications

(21 citation statements)

References 19 publications

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“…Some groups have advocated prolonged use of corticosteroid monotherapy in the management of sarcoidosis [40,41]. However, others have advocated the use of steroid-sparing agents in managing chronic disease [42].…”

Section: Discussionmentioning

confidence: 99%

Delphi consensus recommendations for a treatment algorithm in pulmonary sarcoidosis

et al. 2020

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Pulmonary sarcoidosis presents substantial management challenges, with limited evidence on effective therapies and phenotypes. In the absence of definitive evidence, expert consensus can supply clinically useful guidance in medicine. An international panel of 26 experts participated in a Delphi process to identify consensus on pharmacological management in sarcoidosis with the development of preliminary recommendations.The modified Delphi process used three rounds. The first round focused on qualitative data collection with open-ended questions to ensure comprehensive inclusion of expert concepts. Rounds 2 and 3 applied quantitative assessments using an 11-point Likert scale to identify consensus.Key consensus points included glucocorticoids as initial therapy for most patients, with non-biologics (immunomodulators), usually methotrexate, considered in severe or extrapulmonary disease requiring prolonged treatment, or as a steroid-sparing intervention in cases with high risk of steroid toxicity. Biologic therapies might be considered as additive therapy if non-biologics are insufficiently effective or are not tolerated with initial biologic therapy, usually with a tumour necrosis factor-α inhibitor, typically infliximab.The Delphi methodology provided a platform to gain potentially valuable insight and interim guidance while awaiting evidenced-based contributions.

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Section: Discussionmentioning

confidence: 99%

Delphi consensus recommendations for a treatment algorithm in pulmonary sarcoidosis

et al. 2020

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“…In both these trials, the intervention was added after the patients were documented to be stable on maintenance immunosuppressive and/or immunomodulatory therapy, although the trial by JUDSON et al [17] applied tapering of baseline therapy in the second half of the study (after the primary end-point). It has been suggested that this pre-treatment was responsible for the limited or absent additional benefit of the intervention, and this could also explain the absence of significant improvement on HRQoL and fatigue [31]. This is supported by the study of MILMAN et al [15] in which no additional benefit from adalimumab to stable dosed prednisone and methotrexate was observed on lung function parameters and HRQoL, although it should be noted that the adalimumab dose density was only half of that in the studies by ERCKENS et al [14] and PARISER et al [16].…”

Section: Discussionmentioning

confidence: 99%

The effects of pharmacological interventions on quality of life and fatigue in sarcoidosis: a systematic review

et al. 2020

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AimsMany sarcoidosis patients experience a reduction in health-related quality of life (HRQoL) and a majority of patients report fatigue. Historically, drug trials in sarcoidosis have focused on changes in chest radiographs, lung function parameters and biomarkers, while HRQoL and fatigue have not been the main outcomes examined. We performed a systematic review of the literature to evaluate the existing evidence on the effects of pharmacological interventions on HRQoL and fatigue outcomes.MethodsThe systematic search was performed in Medline and Embase and yielded 15 records covering seven randomised controlled trials and seven single-arm open label studies, which were included in a qualitative synthesis (the results of one study were included in two publications). 12 studies evaluated immunosuppressive and/or immunomodulatory therapies and two studies evaluated stimulants.ResultsNine out of the 14 studies observed positive treatment effects from the interventions on HRQoL and/or fatigue, exceeding the minimal important difference. The risk of bias was generally high with only three studies rated as having a low risk of bias. The results suggest a potential for improvement in HRQoL and/or fatigue in patients with active disease who are either untreated or treated but not yet fully stabilised or therapy refractory.ConclusionMore randomised, double-blind and placebo-controlled trials are needed to expand the evidence base on these important outcome parameters.

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“…First, sarcoidosis-related symptoms usually develop slowly over many weeks to months. 7 This slow development of symptoms is attributable to the slow growth of granulomatous inflammation in sarcoidosis that is initially microscopic, asymptomatic, and undetectable. These microscopic granulomas may eventually extend and coalesce into macroscopic masses that may cause significant symptoms and organ dysfunction.…”

Section: The Initial Screening Step: the Medical History And Physicalmentioning

confidence: 99%

“…These microscopic granulomas may eventually extend and coalesce into macroscopic masses that may cause significant symptoms and organ dysfunction. 7,8 However, there are exceptions where sarcoidosis symptoms may develop rapidly. One such exception occurs when a small focus of sarcoidosis granulomas develops in a strategically vulnerable location in the body, such as the myocardial conducting system or optic nerve; in this situation, symptoms may develop acutely and result in significant morbidity and even death.…”

Section: The Initial Screening Step: the Medical History And Physicalmentioning

confidence: 99%

Screening Sarcoidosis Patients for Occult Disease

Judson

2020

Semin Respir Crit Care Med

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As sarcoidosis may involve any organ, sarcoidosis patients should be evaluated for occult disease. Screening for some organ involvement may not be warranted if it is unlikely to cause symptoms, organ dysfunction, or affect clinical outcome. Even organ involvement that affects clinical outcome does not necessarily require screening if early detection fails to change the patient's quality of life or prognosis. On the other hand, early detection of some forms of sarcoidosis may improve outcomes and survival. This manuscript describes the approach to screening sarcoidosis patients for previously undetected disease. Screening for sarcoidosis should commence with a meticulous medical history and physical examination. Many sarcoidosis patients present with physical signs or symptoms of sarcoidosis that have not been recognized as manifestations of the disease. Detection of sarcoidosis in these instances depends on the clinician's familiarity with the varied clinical presentations of sarcoidosis. In addition, sarcoidosis patients may present with symptoms or signs that are not related to specific organ involvement that have been described as parasarcoidosis syndromes. It is conjectured that parasarcoidosis syndromes result from systemic release of inflammatory mediators from the sarcoidosis granuloma. Certain forms of sarcoidosis may cause permanent and serious problems that can be prevented if they are detected early in the course of their disease. These include (1) ocular involvement that may lead to permanent vision impairment; (2) vitamin D dysregulation that may lead to hypercalcemia, nephrolithiasis, and permanent kidney injury; and (3) cardiac sarcoidosis that may lead to a cardiomyopathy, ventricular arrhythmias, heart block, and sudden death. Screening for these forms of organ involvement requires detailed screening approaches.

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Negative clinical trials in sarcoidosis: failed therapies or flawed study design?

Cited by 31 publications

References 19 publications

Delphi consensus recommendations for a treatment algorithm in pulmonary sarcoidosis

Delphi consensus recommendations for a treatment algorithm in pulmonary sarcoidosis

The effects of pharmacological interventions on quality of life and fatigue in sarcoidosis: a systematic review

Screening Sarcoidosis Patients for Occult Disease

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