Alternatives to Prednisone for Sarcoidosis Treatment Reviewed

A recent review discussed other options in addition to prednisone and methotrexate in the treatment of sarcoidosis, including methotrexate-like antimetabolites, antimalarial agents, adrenocorticotropic hormone (ACTH) gel, biological agents, and antimycobacterial therapy, which is commonly used to treat the tuberculosis.

The review, “Sarcoidosis: treatments beyond prednisone and methotrexate” was published in the journal Expert Review of Respiratory Medicine.

Sarcoidosis is a disease that involves abnormal collections of white blood cells that form lumps known as granulomas. The disease usually affects the lungs (pulmonary sarcoidosis), skin or lymph nodes. Less commonly, it can affect the eyes, liver, heart and brain. The signs and symptoms of the disease depend on the organ involved.

The most common treatment, prednisone, is a glucocorticosteroid, a kind of hormone. It has undesirable side effects, and some cases of sarcoidosis do not improve with treatment. Methotrexate is also commonly prescribed to help reduce the dose of prednisone needed, but 20 to 40% of sarcoidosis cases do not respond to it. In addition, the fear of its toxicity, the need to control the toxic effects, and the approximately six months it takes to have an effect limits its use.

Azathioprine, leflunomide and mycophenolate mofetil (FMO) all act by the same mechanism as methotrexate and may be viable alternatives; However, trials testing these drugs are limited. Azathioprine is considered a viable option, especially among patients who can not tolerate methotrexate. Leflunomide is used in unresponsive cases, and MMF has been less studied for its effects.

Antimalarials (mainly less toxic but less potent hydroxychloroquine) are mainly used in patients with cutaneous and joint involvement, as well as hypercalcemia (high levels of calcium in the blood). But the risk of irreversible eye damage requires close eye follow-up.

Adrenocorticotropic hormone (ACTH) gel has been tested for the treatment of pulmonary sarcoidosis. An ACTHAR gel study showed improvements in 11 of 29 patients (38%) and allowed a reduction of the prednisone dose of more than 50% in 16 patients (55%). However, almost 40% of the patients treated were unable to continue the medication, mainly due to side effects.

Biological agents (agents derived from natural substances) that target TNF-alpha (a factor related to inflammation) are now being introduced in the treatment of sarcoidosis.

One is infliximab, which has been shown to be an effective therapy for sarcoidosis when the lungs, skin, or brain are affected, but also other organs. Adalimumab proved to be effective when the skin is affected. Other anti-TNF agents, such as etanercept and golimumab, do not appear to have the same beneficial effect on sarcoidosis.

Rituximab is a drug that targets B cells, the white blood cells of the immune system, but additional studies are needed to evaluate its effectiveness.

CLEAR therapy (concomitant with levofloxacin, ethambutol, azithromycin and rifampicin), a combination of antibiotics, is an antimycobacterial therapy currently being tested in a phase 2 trial (NCT02024555) in patients with pulmonary sarcoidosis.

“Given the undesirable side effects of glucocorticoids, and the existence of refractory cases, there is widespread recognition that other therapeutic options should be developed or adapted in sarcoidosis,” the researchers wrote.

“Prednisone and methotrexate are well-established medications in the management of sarcoidosis, based on expert opinion and a handful of controlled trials,” they added. “Other antimetabolites (azathioprine, leflunomide, and MMF) and antimalarial agents (hydroxy- chloroquine, chloroquine) are also available for second-line therapy, but further studies are needed to better assess their benefits and risks.

“Lately, anti-TNFα and antimycobacterial therapy have shown promising results in randomized controlled trials, opening new routes for clinical management and research,” the team concluded.