How would you approach rheumatoid arthritis treatment for widespread large rheumatoid nodules but no active synovitis or subjective joint pain?

One needs also to consider drug-induced accelerated nodulosis. I used to see it more often in the 1990s from methotrexate, but since then, it has also been described with other drugs like TNF inhibitors and leflunomide (Patatanian & Thompson, PMID 12222551, Ahmed et al., PMID 11470988, Akiyama et al., PMID 26177173). I have rarely seen accelerated nodulosis during the past 20 years.

Like Dr. @Dr. First Last, if they do not bother the patient and the RA is in remission, I leave them alone. If both...

If asymptomatic, you are always best leaving the nodule alone. If a nodule is irksome (e.g., symptomatic), cutaneous and not associated/adherent to a tendon or ligament, injection is a safe effective treatment. I recommend Ching et al., PMID 1450803, a placebo-controlled trial. Other references are easily found on PubMed. I have tended to see misadventures with alternatives such as excisional biopsy. Widespread nodulosis w/o synovial symptoms (very rare - have only seen a few times) can be manag...