SAN DIEGO – For the first time, a forthcoming evidence-based guideline for the management of psoriatic arthritis recommends tumor necrosis factor inhibitor biologics as first-line therapy.
“Guidelines that have been around for the last several years have been skirting around the fact that there’s really no evidence that methotrexate works for PsA,”, said during a press briefing at the annual meeting of the American College of Rheumatology. “So it’s refreshing and reassuring that when you do an appropriate, evidence-based approach, you finally find the truth in front of you, and you have TNF inhibitors as the first-line treatment. Obviously, they’re not for everybody. There are patients in whom we cannot use TNF inhibitors, either because they don’t like needles, or because they have contraindications to getting these particular needles, but at least we have a recommendation for the use of these drugs as a first-line treatment.”
“At first, I wasn’t a big fan of the idea of the GRADE guidelines because the number of questions blows up so fast, [but] it really makes you focus on what the most common [clinical] settings are,” said another core oversight team member,, a rheumatologist at the University of Pennsylvania, Philadelphia. “These guidelines also reveal the major gap of no head-to-head studies. I think we’ve known that, but this really called that out as important. When we’re making a treatment decision between [drugs] A and B, we need those studies to be able to better understand how to treat our patients, rather than using the data from one trial to make a decision. ... For my patients, I’m excited that I can now use a TNF inhibitor as a first-line agent. When we have patients come in with very severe disease, occasionally they also have severe psoriasis, so we’ve been able to use TNF inhibitors as first-line treatment in some of our patients in Pennsylvania. This differs state by state. But the exciting thing is that they get better so fast and you don’t have to tell them to wait 12 weeks for methotrexate to work.”
The ACR/NPF guideline is currently under peer review and is expected to be published in Arthritis & Rheumatology, Arthritis Care & Research, and the Journal of Psoriasis and Psoriatic Arthritis in the spring or summer of 2018. It focuses on common PsA patients, not exceptional cases. It includes recommendations on the management of patients with active PsA that is defined by the patients’ self-report and judged by the examining clinician to be caused by PsA, based on the on the presence of at least one of the following: actively inflamed joints; dactylitis; enthesitis; axial disease; active skin and/or nail involvement; and/or extra-articular manifestations such as uveitis or inflammatory bowel disease. Authors of the guideline considered cost as one of many possible factors affecting the use of the recommendations, but explicit cost-effectiveness analyses were not conducted. Also, since the NPF and the American Academy of Dermatology are concurrently developing a psoriasis treatment guideline, the treatment of skin psoriasis was not included in the guideline.
According to the guideline’s principal investigator, professor of medicine and epidemiology at the University of Alabama at Birmingham, the guideline will include 80 recommendations, 75 (94%) that are rated as “conditional,” and 5 (6%) that are rated as “strong,” based on the quality of evidence in the existing medical literature. “Most of our treatment guidelines rely on very low-to-moderate quality evidence, which means that there needs to be an active discussion between the physician and the patient with regard to which treatment to choose,” said Dr. Singh, who is also a staff rheumatologist at the Birmingham Veterans Affairs Medical Center and who led development of the 2012 and 2015 ACR treatment guidelines for RA. “When you’re not choosing the preferred treatment, there are defined specific recommendations under which that second treatment may be preferred over the first treatment.”
During a separate session at the meeting, Dr. Singh unveiled a few of the draft recommendations. One calls for using a treat-to-target strategy over not using one. In the setting of immunizing patients who are receiving a biologic, another recommendation calls for clinicians to start the indicated biologic and administer killed vaccines (as indicated) in patients with active PsA rather than delaying the biologic to give the killed vaccines. In addition, delaying the start of the indicated biologic is recommended over not delaying in order to administer a live attenuated vaccine in patients with active PsA. When patients continue to have with active PsA despite being on a TNF inhibitor, the draft guideline recommends switching to a different TNF inhibitor rather than an IL-17 inhibitor, an IL-12/IL-23 inhibitor, abatacept (Orencia), tofacitinib (Xeljanz), or adding methotrexate. If PsA is still active, the guideline recommends switching to an IL-17 inhibitor instead of an IL-12/IL-23 inhibitor, abatacept, or tofacitinib. If PsA is still active, the guideline recommends switching to an IL-12/IL-23 inhibitor over abatacept or tofacitinib.
The guideline also includes suggestions for nonpharmacologic treatments, including recommending low-impact exercise over high-impact exercise, occupational therapy, physical therapy, and weight loss. It also includes a strong recommendation to provide smoking cessation advice to patients.
Dr. Singh acknowledged significant research gaps in the current PsA medical literature, including no head-to-head comparisons of treatments. He said that the field also could benefit from specific studies for enthesitis, axial disease, and arthritis mutilans; randomized trials of nonpharmacologic interventions; more trials of monotherapy vs. combination therapy; vaccination trials for live attenuated vaccines; trials and registry studies of patients with common comorbidities, and studies of NSAIDs and glucocorticoids, to define their role.
Possible topics for future PsA guidelines, he continued, include treatment options for patients for whom biologic medication is not an option; use of therapies in pregnancy and conception; incorporation of high-quality cost or cost-effectiveness analysis into recommendations; and the role of other comorbidities, such as fibromyalgia, hepatitis, depression/anxiety, malignancy, and cardiovascular disease.
“Evidence-based medicine needs to be practiced, even in situations where it’s difficult to get a drug,” Dr. Gladman said. “One of the things we hope will happen in the near future is that companies will start doing head-to-head studies, to help us support evidence-based recommendations in the future.”
None of the speakers reported having relevant financial disclosures.