When do I know it is time to consider a biologic?

First of all, it is of utmost importance that you communicate these issues to the physician treating your illness. Any discontinuation of any medication should ALWAYS be a two-way decision, not one made on your own. It is not possible for me to fully understand how the Plaquenil or the Methotrexate may or may not have been helping you, but your physician can monitor your disease activity by looking at how much joint tenderness or swelling you are experiencing as well as looking at x-rays or other imaging studies to determine if joint damage has occurred. Patients taking even standard traditional disease modifying drugs have less damage than those simply being treated with medications to reduce symptoms such as ibuprofen. In those patients who have inflammation and/or damage of the joints despite these medications, a biologic agent is an appropriate next step and when used appropriately can control both the symptoms and minimize or even eliminate any further damage. If you are an appropriate candidate for these drugs and have no other illnesses that would put you at risk for complications, then it's time to move on. Reading between the lines, if you are also taking Cymbalta, I wonder if you also may have fibromyalgia, which makes assessment of rheumatoid arthritis disease activity exceedingly difficult. Cymbalta reduces symptoms in some patients but does not have any effect on inflammation of joints or on joint damage. The main message is I would like you to work TOGETHER with your doctor on your treatment plan, and that you should be taking SOMETHING, whether that be a biologic drug, a traditional disease modifying drug, or both, depending on the above variables. I hope that helped.