Sarcoidosis: Updates on therapeutic drug trials and novel treatment approaches

Abstract

Sarcoidosis is a systemic granulomatous inflammatory disease of unknown etiology. It affects the lungs in over 90% of patients yet extra-pulmonary and multi-organ involvement is common. Spontaneous remission of disease occurs commonly, nonetheless, over 50% of patients will require treatment and up to 30% of patients will develop a chronic progressive non-remitting disease with marked pulmonary fibrosis leading to significant morbidity and death. Guidelines outlining an immunosuppressive treatment approach to sarcoidosis were recently published, however, the strength of evidence behind many of the guideline recommended drugs is weak. None of the drugs currently used for the treatment of sarcoidosis have been rigorously studied and prescription of these drugs is often based on off-label” indications informed by experience with other diseases. Indeed, only two medications [prednisone and repository corticotropin (RCI) injection] currently used in the treatment of sarcoidosis are approved by the United States Food and Drug Administration. This situation results in significant reimbursement challenges especially for the more advanced (and often more effective) drugs that are favored for severe and refractory forms of disease causing an over-reliance on corticosteroids known to be associated with significant dose and duration dependent toxicities. This past decade has seen a renewed interest in developing new drugs and exploring novel therapeutic pathways for the treatment of sarcoidosis. Several of these trials are active randomized controlled trials (RCTs) designed to recruit relatively large numbers of patients with a goal to determine the safety, efficacy, and tolerability of these new molecules and therapeutic approaches. While it is an exciting time, it is also necessary to exercise caution. Resources including research dollars and most importantly, patient populations available for trials are limited and thus necessitate that several of the challenges facing drug trials and drug development in sarcoidosis are addressed. This will ensure that currently available resources are judiciously utilized. Our paper reviews the ongoing and anticipated drug trials in sarcoidosis and addresses the challenges facing these and future trials. We also review several recently completed trials and draw lessons that should be applied in future.

Interstitial lung disease: a review of classification, etiology, epidemiology, clinical diagnosis, pharmacological and non-pharmacological treatment

“…ILDs are a complex group of diseases with diverse causes, meaning the most effective treatments will vary from patient to patient and depend on the specifics of their condition ( 119 ). For instance, sarcoidosis is managed primarily through immunosuppression ( 120 , 121 ). Systemic sclerosis-associated (SSc) ILD is treated with mycophenolate mofetil, tocilizumab, and cyclophosphamide.…”

“…They have broad anti-inflammatory and immunosuppressive effects. However, they are associated with significant side effects, such as weight gain, indigestion problems, restlessness, sweating, and mood changes ( 120 ). These side effects are particularly notable when the substances are used in high doses or for prolonged periods.…”

Diversity and disparity in the treatment and care of sarcoidosis

“…They have also been associated with significant reduction in HRQoL [60,61] ]. TNF-a inhibitors are extremely expensive and can be very challenging to acquire even for patients with some insurance [63]. Delay in seeking care resulting in presentation with more advanced, more severe disease Worse symptom burden resulting from delayed presentation Reduced access to specialty and subspeciality care leading to delays in diagnosis Difficulty affording medications leading to medication non-compliance and higher likelihood of using cheaper steroid only regimens More likely to have no insurance or public insurance reducing access to care and causing difficulty keeping regular follow-up appointments More likely to miss doctor's appointments resulting in more irregular followup, and higher risk of missing new organ involvement and medication toxicity Educational barriers to care may cause:…”

“…It is also necessary to identify and address systemic socioeconomic barriers to clinical trial participation so as to improve participation for patients of lower SES. Simplifying research protocols, providing flexible hours for clinical trial visits, providing child and elder care, arranging transportation to distant trial sites, and ensuring adequate reimbursement for time spent during trial visits may go a long way towards improving clinical trial participation in African Americans, females, and patients of lower SES [63,91,93].…”

“…Third-line therapy includes infliximab and adalimumab both of which are inhibitors of tumor necrosis factor-α (TNF-α) [54 ▪▪ ]. TNF-α inhibitors are extremely expensive and can be very challenging to acquire even for patients with some insurance [63].…”