In the last 2 decades, biologic and small-molecule medications have led to a paradigm shift in the treatment approach of various systemic inflammatory conditions, such as psoriasis, psoriatic arthritis, and rheumatoid arthritis (RA). These conditions are prevalent and managed by healthcare professionals in various specialties.1,2 As a result, the number of providers using biologics and small-molecule medications has increased since their initial approval by the FDA.
Patients who suffer with psoriasis, psoriatic arthritis, and RA often have difficulty maintaining activities of daily living without treatment. The earliest possible treatment improves patient quality of life. Many specialists who treat these conditions are facing significant workforce shortages, resulting in patients waiting an extended time for an appointment.3-8 Primary care providers can assist these specialists by obtaining the needed premedication screening tests for patients who may benefit from biologic, small-molecule, or other immunosuppressive medications. This may reduce the time between the first specialist visit and the patient beginning the most effective treatment.
CONDITIONS AMENABLE TO BIOLOGICS
The prevalence of psoriasis among US adults is about 3.2%. An estimated 7.4 million US adults had psoriasis in 2013.1 The prevalence of psoriatic arthritis among US adults is about 0.25% (an estimated 578,000 adults).9 RA has a prevalence of about 0.6% in the United States, affecting about 1.29 million people.2
Psoriasis and inflammatory arthritis significantly affect patient quality of life.10-12 Because of the prevalence of these conditions, specialist workforce issues that result in long wait times for initial specialist evaluation, early patient screening by primary care providers can help ensure the best possible transition by providing specialists with screening results and preparing patients to begin appropriate treatment upon transfer to specialty care.
This article describes the latest guidelines for screening patients before they start biologic or small-molecule medications, and focuses on the dermatologic and rheumatic conditions for which these medications are used. Gastroenterology, oncology, and other medical specialties also use biologics; these prebiologic screening principles also may be applicable to conditions and diseases managed by other specialists.
IMMUNOSUPPRESSION AND BIOLOGICS
The early, broad (innate) immune response followed by the more specific and precisely targeted (adaptive) immune response work together to provide patients with formidable protection. However, this potent lifesaving system can turn to life-threatening disease if dysfunctional autoimmunity develops. Scientists and clinicians have focused on the key players in immune pathways, including cytokines, interleukins, B cells, and T cells, as they sought to develop improved therapeutic options that more precisely suppress the abnormal autoimmune response, leaving the beneficial immune response intact (Figure 1). This effort is expected to continue to be a focus of future scientific discovery.
In contrast to chemically synthesized small-molecule medications, biologics are larger and more complex molecules created from living things, such as human or animal cells and microorganisms. Generally, biologics are more complex structurally than chemically synthesized drugs. Manufacturing biologics requires attention to detail in environments that control for temperature and aseptic technique monitoring.13 Biologics first became available as a potential therapeutic option in the late 1990s with the approval of etanercept, and shortly thereafter infliximab, for RA. Since these initial approvals, multiple other biologics have been approved for various indications (Table 1).14-28
In the past 5 years, small-molecule medications such as tofacitinib and apremilast have been approved for dermatologic and rheumatologic conditions. Although these medications are not classified as biologics, like the biologics they are highly selective for immune system molecular targets and are considered along with biologics to be targeted immune modulators. They are used to treat many of the same conditions as biologics, and therefore, a discussion of the screening requirements for these products will be included in this article.
Because targeted immune modulators are potent medications with the potential for overlapping adverse reactions, many of which are preventable, patients should have baseline laboratory and vaccination updates before beginning treatment. When making treatment decisions, consider patient comorbidities; severity of joint, skin, and organ involvement; and informed patient preference. Comorbidities such as heart failure, demyelinating disease, pulmonary disease, or history of current or recurrent infections affect the choice of biologic or small-molecule medication that is best for each patient.
Although biologics and small-molecule medications have increased the options available for patients with autoimmune and autoinflammatory disease, most treatment approaches begin with traditional disease-modifying medications (such as methotrexate, hydroxychloroquine, sulfasalazine, and leflunomide) or topicals for psoriasis. Appropriate screening laboratory and vaccinations are indicated before patients begin traditional disease-modifying medications.29-31
As with all medications, the potential risks must be weighed against the potential benefits. Biologics and small-molecule medications provide additional options for pain control, prevention of destructive joint changes, improved quality of life, improved function, and improved feelings of self-worth. However, these drugs pose the risk of injection site or infusion reactions, infection, malignancy, flare or discovery of demyelinating disease, heart failure, cytopenias, and drug-induced syndromes. These drugs also are expensive.32
THE NEEDED EVALUATION
Patients being considered for therapy with biologic or small-molecule medications should have the following evaluations:
Obtain a hepatitis B core antibody, hepatitis C antibody, and hepatitis B DNA depending on results of other serologies or in patients with known hepatitis B virus. Certain types of biologics, including tumor necrosis factor (TNF) inhibitors and anti-CD 20 agents, can reactivate hepatitis B.33,34 Reactivation seems to be more likely in patients with positive hepatitis B surface antigens who have taken TNF inhibitors. Prescribers must use caution when prescribing moderate doses of corticosteroids (prednisone at 20 mg or more per day or equivalent), which also may contribute to hepatitis B reactivation. In patients with known hepatitis B and indications to treat their comorbid inflammatory condition, clinicians should consider antiviral therapy. Monitoring hepatitis B DNA levels also may be warranted while patients are taking biologics, as hepatitis B DNA increase occurs before alanine aminotransferase (ALT) elevation in hepatitis B reactivation.
Current evidence suggests that patients with hepatitis C can be treated with biologics. Guidelines suggest that the clinician prescribing the biologic should comanage patients with hepatitis C who require biologics with gastroenterologists or hepatologists and consider treatment with antivirals.26
An additional reason to screen for hepatitis B and C is the fact that positive rheumatoid factors can be associated with hepatitis viral infections.35,36 Ordering a cyclic citrullinated peptide antibody may aid in distinguishing patients with RA from those with a positive rheumatoid factor associated with a hepatitis B or C infection.37-40 False-positive rheumatoid factors also are possible in healthy patients.41-43
Tuberculosis (TB) screening
Obtain a TB skin test or interferon-gamma release assay for patients expecting to start biologics or small-molecule medications for psoriasis, psoriatic arthritis, or RA.26-28,34,44 The interferon-gamma release assay is preferred for patients who have received the bacillus Calmette-Guérin vaccination.
If a TB screening workup is negative, the patient can proceed with biologic or small-molecule medications. If the initial TB screening workup is positive, additional workup, including a chest radiograph, is warranted. If the chest radiograph is unremarkable, a latent TB infection is assumed and appropriate antitubercular treatment is started. Biologic medications can be started at least 1 month after the antitubercular regimen is started.
If the chest radiograph indicates active TB, obtain sputum cultures for acid-fast bacteria. If sputum cultures are negative, the patient can begin biologic medications at least 1 month after starting the appropriate antituberculin antibiotics. If an active TB infection is confirmed by sputum culture, the patient should complete the antitubercular antibiotic regimen before beginning biologic or small-molecule medications.
Some prescribers also screen for TB with an annual skin test or interferon-gamma release assay, especially for patients receiving who are at high risk for TB exposure, such as healthcare workers, prisoners, and those living or traveling in high-prevalence areas. An annual skin test is recommended in the dermatology guidelines.44,45 An initial chest radiograph or serial (annual) chest radiographs also may be considered for patients at high risk for TB exposure.
Due to the immune system status of patients with psoriasis, psoriatic arthritis, and RA, and immunosuppressive properties of medications used to treat these conditions, vaccinations are highly recommended. Certain vaccinations, such as pneumococcal and the herpes zoster vaccination, often are recommended earlier than usual based on a patient's age. For example, current American College of Rheumatology treatment guidelines for patients with RA suggest administering the herpes zoster vaccination at age 50 years and older, compared with the CDC's recommendation of age 60 years.31
Ideally, vaccinations should be administered before starting traditional disease-modifying drugs, biologics, or small-molecule medications, in theory for the most ideal immune response to these vaccinations.
Killed and recombinant vaccinations (such as pneumococcal, influenza in season, hepatitis B, and human papillomavirus) are recommended for patients taking biologics or small-molecule medications. Live, attenuated vaccinations (such as herpes zoster) are not recommended for patients taking biologic or small-molecule medications.
The pneumococcal polysaccharide vaccine (PPSV23) and pneumococcal conjugate vaccine (PCV13) should be given according to administration protocols to patients considering or using biologics or small-molecule medications, regardless of patient age.
Patients on biologics or small-molecule medications who travel internationally require special consideration. Patients and providers should discuss how to manage pharmacologic treatment when live, attenuated vaccinations are required for travel to areas of the world requiring specified vaccinations. Consult the current CDC guidelines or a travel medicine specialist. Patients using biologics or small-molecule medications may need to discontinue these treatments for a period of time to receive the vaccination; clinicians should review and follow the recommendations found in the drug's prescribing information.11-25 Guidelines recommend that live vaccines should be administered more than 4 weeks before patients begin a biologic or small-molecule medication.46 This improves the patient's immune response to the virus and reduces the risk of disseminating the live virus.47
Biologic and small-molecule medications have had and will continue to have a substantial role in the treatment of psoriasis, psoriatic arthritis, RA, and other inflammatory and autoimmune conditions. Clinicians referring patients to dermatologists and rheumatologists can prepare patients with psoriasis, psoriatic arthritis, and RA for expected treatment with immunosuppressant drugs. This preparation may include obtaining hepatitis serologies and TB screenings as well as ensuring appropriate vaccinations are administered before the initial specialty visit (Table 2). Although many patients with psoriasis, psoriatic arthritis, and RA may not immediately begin a biologic or small-molecule medication, having the requisite screening and preventive medicine studies performed will help specialists prescribe the appropriate therapy. Once these steps have been accomplished, primary care and specialty providers must communicate and provide documentation to support the completion of the necessary pretherapy steps to ensure best patient outcomes.
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Keywords:Copyright © 2018 American Academy of Physician Assistants
biologics; small-molecule medications; systemic inflammatory conditions; psoriasis; rheumatoid arthritis; psoriatic arthritis