Q: How do treatment recommendations differ for patients who are DMARD-naïve vs those who have already been treated with 1 or more DMARDs? How does low vs moderate to high disease activity factor into this equation? 

It is important to note the level of evidence for each of the recommendations. Many treatment recommendations are based on a low level of evidence or are just conditional recommendations. In my view, current rheumatoid arthritis (RA) treatment guidelines do not fully address individual differences among patients who fall in the moderate to high disease activity category. Additionally, I believe that non–tumor necrosis factor (non-TNF) biologics can be an appropriate choice as a first biologic. Consider a patient with 15 to 20 tender, swollen joints and a patient with 3 tender, swollen joints. According to contemporary guidelines, both individuals should be started on methotrexate (MTX); however, there are now other treatment options available that are not recommended for disease-modifying antirheumatic drug (DMARD)–naïve individuals, even when disease activity is very high. These include several non-TNF biologic therapies (eg, abatacept, rituximab, sarilumab, tocilizumab) and targeted synthetic DMARDs (eg, tofacitinib, baricitinib), the latter of which are highly active and can start to produce a response within 1 week. Many of these agents have been shown to have improved efficacy relative to that of MTX in terms of reducing signs and symptoms of RA and inhibiting the progression of structural joint damage. Consider a patient with more than 10 to 15 tender, swollen joints, who has had podiatric surgery, and who presents with flexion contracture of the elbows. Are you really going to prescribe just MTX? Cost concerns need to be informed not only by the cost of the drug, but also by the overall costs to the health care system. In our experience, patients on these newer agents are achieving great responses, and they are almost in remission. Additionally, we are particularly aggressive in patients who are on steroids. We now know that even 7.5 mg of prednisone is associated with a risk of infection.

The guidelines are very appropriate, for the most part. At this point in time, I do not think that there is any indication for a biologic to be used in a patient with RA before conventional synthetic DMARDs (csDMARDs). You can try conventional therapy and not lose ground in terms of clinical response or radiographic progression for up to 6 months, as nicely shown by the Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) trial. One of the major problems, however, is that few practitioners in the United States currently use csDMARDs optimally, and that is unfortunate for both the patient and for our insurance premiums. While newer agents such as tofacitinib and baricitinib have shown improved efficacy compared with MTX, we do not know that they are superior to MTX in terms of cardioprotection and when toxicities are factored in over the long-term. Efficacy is important, but so is toxicity. Sooner or later, we also need to consider costs—I favor sooner. I will not start my patients on a biologic as first-line therapy based on the current available evidence. That said, we want patients to get their disease under control, and if they still have active joints despite the best use of csDMARDs, then they definitely should be on a biologic. Further, if patients are requiring prednisone at all, that is an indication to escalate therapy. It would be great to have data showing that induction therapy with biologics such as anti-TNF agents (ie, to stop disease activity before the MTX takes effect) will improve clinical outcomes. I tell my patients that our first goal or priority is to get their disease in remission, and our second goal is to make sure that they are not on prednisone. What we really need are parameters that tell us which patients are going to respond to which therapies. Also, a “thermostat” for TNF, interleukin 6, or other cytokine would be very useful, but we do not currently have that.

I see a continuum of patients, from young children with juvenile arthritis to older adults with long-standing RA. For juvenile arthritis, consensus treatment plans have been developed as guidelines for treatment. In pediatrics, we appreciate the need to be cautious in younger age groups, but at the same time we are also often quite aggressive with our treatment. This is, in part, because younger patients could have arthritis for the rest of their lives; therefore, it is our job to ensure that they maintain healthy joints without erosions in order to optimize their long-term health and well-being. There are many different types of inflammatory arthritis and disease subsets in the pediatric population. There is some thought that if you treat juvenile arthritis more aggressively earlier in the course of the disease, you can change the course of the disease down the line, making it easier to treat long-term. Some data support that aggressive treatment with biologics may improve long-term outcomes in certain disease subsets, but this question remains to be answered more generally. An individualized approach to treatment is also important, regardless of age group. Some patients, especially those who travel frequently, may find that biologic agents are inconvenient because of their need for refrigeration. Others may have needle phobia and prefer oral medication for that reason. And for some, it might come down to what is covered by insurance. Some insurance companies are requiring failure on triple csDMARD therapy before a patient can be approved for an anti-TNF agent. It is certainly not a one-size-fits-all proposition, and specific patient characteristics may also be important in your approach. For instance, because there are data showing that obesity and smoking can negatively influence an individual’s treatment response, your approach to treating patients with RA who are obese and who smoke should be tailored to focus on weight loss and smoking cessation, in addition to disease-modifying therapy.