Treatment Guidelines for JIA

By Jill Tyrer | March 23, 2022

A panel of physicians, patients, caregivers and others recently updated two sets of guidelines about the best course of treatment for several forms and subsets of juvenile idiopathic arthritis (JIA).

The American College of Rheumatology (ACR) and its partners, including the Arthritis Foundation, regularly update treatment guidelines. A panel of experts and stakeholders reviews the body of evidence and the most recent research findings to compile the best practices in treating rheumatic diseases.

These updates focus on drug therapies for oligoarthritis, JIA that affects the temporal mandibular joint (TMJ, the jaw), and systemic JIA (sJIA). They also address how to approach reducing or discontinuing medications in patients whose disease is no longer active.

Among the most significant changes are recommendations to minimize or eliminate the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids. Although both have been mainstay treatments in the past, they have potentially harmful effects, and safer alternatives are now available. Another notable change is the recommendation to use a biologic as initial therapy for systemic JIA after trying and failing a short course of NSAIDs, although there are lingering concerns about the potential side effect of a serious lung disease.

These updates complement the 2019 ACR guidelines for treating JIA, which focused on different facets of the disease, including polyarthritis and the eye disease uveitis.

The panel’s recommendations are either strong or conditional, based on the strength of the evidence. Much of the evidence was not strong (in many cases because there is simply a lack of evidence), so many of the recommendations are conditional. While the recommendations are useful tools for doctors as well as patients and caregivers, every case is unique, so you should work closely with the doctor to determine the best treatment course for your child.

Oligoarthritis

Oligoarthritis refers to a subset of JIA that is not systemic and that involves four or fewer joints, usually large ones, like knees, ankles or elbows. The most common form of JIA, it is often mild, but is most often associated with the eye disease uveitis.

Treatment recommendations include:

• Intra-articular glucocorticoids (corticosteroid shots into affected joints) are strongly recommended with initial treatment, preferably using the corticosteroid triamcinolone hexacetonide (Hexatrione).
• A regimen of NSAIDs is conditionally recommended.
• If the injections and NSAIDs don’t have an adequate effect, then an oral conventional synthetic disease-modifying antirheumatic drug (DMARD) is strongly recommended. Methotrexate is recommended over the alternatives.
• Oral corticosteroids are conditionally recommended against. If one is used — until a DMARD takes effect, for instance — it should be at the lowest possible dose for the shortest possible time.
• If there is still not an adequate response after trying at least one conventional DMARD, like methotrexate, then a biologic medication is strongly recommended.

TMJ Arthritis

JIA that affects the TMJ, or the jaw, is especially problematic because it impedes the child’s ability to eat, drink, speak and care for their oral health. TMJ arthritis is not always painful, but it still needs to be treated to protect jaw function. NSAIDs and corticosteroid shots may be sufficient to treat TMJ, but “rapid escalation” to a DMARD or biologic may be necessary “given the impact and destructive nature of TMJ arthritis,” the guideline authors write.

Recommendations for TMJ in JIA include:

• Trying an NSAID regimen as initial therapy is conditionally recommended.
• Including corticosteroid shots in the jaw as part of the initial treatment is conditionally recommended.
• Taking corticosteroids orally is conditionally recommended against.
• If NSAIDs and steroid shots don’t have an adequate response, a conventional DMARD is strongly recommended, and methotrexate is conditionally preferred over leflunomide.
• If an adequate response still isn’t achieved with at least one conventional DMARD, a biologic is conditionally recommended.

Systemic JIA

Systemic JIA is a severe form of JIA that has effects beyond joints, resulting in fever, rash and potential impacts on internal organs. It occurs with or without macrophage activation syndrome (MAS), a life-threatening complication that involves a hyperactive but ineffective immune system and blood disorders among other effects. Patients should be evaluated and monitored for infection, which can trigger MAS at any point during the disease.

Recommendations for sJIA without MAS include:

• Biologics called interleukin-1 (IL-1) inhibitors or IL-6 inhibitors alone are conditionally recommended as initial therapy.
• NSAIDs are conditionally recommended as initial treatment.
• Oral corticosteroids are conditionally recommended against as initial treatment.
• Conventional DMARDs are strongly recommended against as the sole initial therapy.
• If NSAIDs and corticosteroids (if used) aren’t adequate, IL-1 or IL-6 inhibitors are strongly recommended over any single or combination of conventional DMARDs.
• If the IL-1 or IL-6 inhibitor doesn’t get an adequate response, then another biologic or a conventional DMARD is strongly recommended rather than long-term corticosteroids.

Recommendations for sJIA with MAS include:

• Treatment with IL-1 or IL-6 inhibitor biologics is conditionally recommended over DMARDs called calcineurin inhibitors (like cyclosporine, tacrolimus or voclosporin).
• Corticosteroids are conditionally recommended as part of initial therapy (at the lowest dose and for the shortest time possible).
• For residual effects or inadequate response to IL-1 or IL-6 inhibitors, another biologic or conventional DMARD is strongly recommended over long-term corticosteroids.

Reducing or Eliminating Medications

In sJIA either with or without a history of MAS, once the disease has become inactive,

• Use of corticosteroids is strongly recommended to be reduced and discontinued.
• Use of biologics is conditionally recommended to be reduced and/or discontinued.

These guidelines, which address “Nonpharmacologic Therapies, Medication Monitoring, Immunizations, and Imaging,” complement the pharmacological recommendations above as well as the 2019 guidelines. As above, a conditional recommendation does not necessarily mean it isn’t advised, just that the evidence may be lacking. These guidelines were included at the request of patients and caregivers, and mental health guidelines will be considered for future guidelines.

• Physical and occupational therapy are conditionally recommended to maintain or improve range of motion, strength and endurance, as well as to prevent injury and encourage participation in daily and recreational activities.
• Discussing a healthy, age-appropriate diet is strongly recommended.
• Using a specific diet to treat JIA is strongly recommended against.
• Using herbs and other supplements to treat JIA is conditionally recommended against.

Medication Monitoring

The panel weighed the potential risks, pain and inconvenience of exposing a child with JIA to repeated blood draws and other lab tests against the risks of medication toxicity and side effects. Some of the highlights from the full recommendations follow:

• Baseline testing is conditionally recommended to help identify potential side effects or other reasons the medication may be inappropriate.
• Before starting methotrexate or leflunomide, a pregnancy test should be considered as well as potential contraceptive counseling.
• A complete blood test and liver function test in the first one to two months after starting and every three to four months thereafter are conditionally recommended for sulfasalazine (Azulfidine), leflunomide (Arava), tocilizumab (Actemra), anakinra (Kineret), tofacitinib (Xeljanz) and canakinumab (Ilaris).
• With methotrexate, monitoring complete blood count, liver and renal function one to two months after starting and every three to four months after is strongly recommended. If liver function is elevated or neutrophil or platelet count is down, decreasing the dose is conditionally recommended.
• Use of folic acid or folinic acid with methotrexate is strongly recommended.
• For tofacitinib, if monitoring reveals “abnormalities of concern,” it is strongly recommended that it be changed or discontinued.
• If exposure to tuberculosis (TB) is a risk, screening for the disease is conditionally recommended before starting a biologic or DMARD.

Immunizations

In general, children with JIA should receive vaccinations according to national vaccination schedules. “Multiple cohort studies have demonstrated that most children with JIA mount a protective response after immunizations and that immunizations do not cause disease flare,” the authors wrote.

• It is strongly recommended that all children with JIA, including those on immunosuppressants (including DMARDs, biologics or corticosteroids), receive inactivated flu shots annually. They should not receive the FluMist nasal spray, which is a live vaccine.
• All appropriate immunizations are strongly recommended for children with JIA who are not on immunosuppressants.
• Inactivated vaccines are strongly recommended for those who are on immunosuppressants.
• Live vaccines are conditionally recommended against for those on immunosuppressants.
• For children with JIA who haven’t been vaccinated for measles, mumps, rubella, and/or varicella, immunization is conditionally recommended before starting immunosuppressants.
• Vaccines are strongly recommended for those who live in the same household as a child receiving immunosuppressants.

Imaging

• Using radiography to detect active synovitis or enthesitis before more advanced imaging methods is strongly recommended against.
• Using imaging to administer shots into joints is conditionally recommended.