6-MP is metabolized analogously to natural purines, giving thioguanosine triphosphate (TGTP) and thiodeoxyguanosine triphosphate (TdGTP) via thioinosine monophosphate (TIMP) and several further intermediates. On a second path, the sulfur atom of 6-MP and TIMP is methylated. The end products of azathioprine metabolism are thiouric acid (38%) and various methylated and hydroxylated purines, which are excreted via the urine. Mechanism of action
Azathioprine inhibits purine synthesis. Purines are needed to produce DNA and RNA. By inhibiting purine synthesis, less DNA and RNA are produced for the synthesis of white blood cells, thus causing immunosuppression. Azathioprine is converted within tissues to 6-MP, some of which is converted, in turn, to 6-thioguanine by the addition of an amino group. Both 6-MP and 6-thioguanine are conjugated with ribose, and then phosphorylated to form the nucleotides  thioinosinic acid and thioguanylic acid, respectively. These nucleotides masquerade, respectively, as inosinic acid and guanylic acid; the former is the starting point for purine nucleotide biosynthesis, while the latter is one of the building blocks of DNA and RNA. The nucleotides are  incorporated into newly synthesized (but nonfunctional) DNA, halting replication. The nucleotides act to inhibit glutamine-phosphoribosyl pyrophosphate amidotransferase (GPAT), one of the enzymes involved in purine biosynthesis, one of the earlier steps in the synthesis of DNA and RNA. They achieve GPAT inhibition through a form of negative feedback called product inhibition.
Etanercept, on the other hand, has failed to demonstrate any significant efficacy in people with uveal sarcoidosis in a couple of clinical trials. Likewise golimumab has failed to show any benefit in those with pulmonary sarcoidosis. One clinical trial of adalimumab found treatment response in about half of subjects, which is similar to that seen with infliximab, but as adalimumab has better tolerability profile it may be preferred over infliximab. Specific organ treatments
Ursodeoxycholic acid has been used successfully as a treatment for cases with liver involvement. Thalidomide has also been tried successfully as a treatment for treatment-resistant lupus pernio in a clinical trial, which may stem from its anti-TNF activity, although it failed to exhibit any efficacy in a pulmonary sarcoidosis clinical trial. Cutaneous disease may be successfully managed with antimalarials (such as chloroquine and hydroxychloroquine) and the tetracycline antibiotic, minocycline. Antimalarials have also demonstrated efficacy in treating sarcoidosis-induced hypercalcemia and neurosarcoidosis. Long-term use of antimalarials is limited, however, by their potential to cause irreversible blindness and hence the need for regular ophthalmologic screening. This toxicity is usually less of a problem with hydroxychloroquine than with chloroquine, although hydroxychloroquine can disturb the glucose homeostasis.Recently selective phosphodiesterase 4 (PDE4) inhibitors like apremilast (a thalidomide derivative), roflumilast, and the less subtype-selective PDE4 inhibitor, pentoxifylline, have been tried as a treatment for sarcoidosis, with successful results being obtained with apremilast in cutaneous sarcoidosis in a small open-label study.