Treatment Considerations and Recommendations for Cystic Fibrosis

Cystic fibrosis (CF) is a genetic disease that affects approximately 300,00 U.S. individuals. It is a chronic, progressive, life-shortening disease that primarily affects the lungs and pancreas, and the majority of patients are now diagnosed at birth due to newborn screenings. In 2018, the median predicted survival of patients with CF was 44.4 years. A complication of CF includes multiorgan disease, affecting the respiratory, digestive, endocrine, and reproductive systems, as well as having mental health implications.

During a presentation at the Asembia 2020 Summit, Rachel Espinosa, PharmD, CF medication therapy management pharmacist at the University of Minnesota Cystic Fibrosis Center in Minneapolis, MN, and Emily Stephan, PharmD, advanced patient care pharmacist of specialty pharmacy and CF at Nationwide Children’s in Columbus, OH,discussed treatment options and management of patients with CF.

The treatment burden is high in this patient population. Patients with CF often need intravenous antibiotics to treat pulmonary exacerbations and will routinely require higher doses of antibiotics to achieve therapeutic levels. Common medication categories include pancreatic enzymes, fat-soluble vitamins, anti-inflammatories, bronchodilators, mucolytics, inhaled antibiotics, and CF transmembrane conductance regulator (CFTR) modulators.

Approximately 90% of patients with CF have exocrine pancreatic insufficiency, fat malabsorption secondary to decreased pancreatic enzyme production. Patients require pancreatic enzyme replacement therapy, and nutrition plays an important role for these patients. Many patients require dietary supplementation, either orally or via feeding tubes, to get adequate nutrition due to malabsorption issues.

Chest physical therapy is performed daily, normally at least twice daily, to clear the mucus and reduce the risk of infection and improve lung function. Bronchodilators are also used prior to mucolytics and/or antibiotics to prevent bronchospasm associated with inhaled therapies.

CFTR modulators correct the underlying CFTR channel defect, and newly emerging CFTR modulators have demonstrated statistically significant positive pulmonary outcomes. Ivacaftor is a first-in-class CFTR modulator approved in 2012 for patients aged six months and older with one mutation in the CFTR gene. In the phase III STRIVE trial, ivacaftor resulted in a 10.6-point increase in mean percent predicted forced expiratory volume in one second (FEV1) from baseline through week 24 (P<0.0001). Lumacaftor/ivacaftor is a combination CFTR corrector and potentiator available as a fixed dose powder packet or tablet and is indicated for patients who are F508del homozygous. The TRAFFIC and TRANSPORT clinical trials showed that lumacaftor/ivacaftor resulted in 2.6 percentage point and 3.0 percentage point, respectively, absolute change in FEV1 at week 24 versus placebo. Tezacaftor/ivacaftor is a combination CFTR corrector and potentiator that is available as fixed-dose tablets and is indicated for patients who are F508del homozygous or have at least one mutation in CFTR. The EVOLVE trial observed a 4% mean absolute improvement in FEV1 at week 24 with tezacaftor/ivacaftor, and the EXPAND trial observed a 6.8% mean absolute improvement in FEV1 versus placebo (P<0.0001).

Elexacaftor/tezacaftor/ivacaftor is a combination CFTR corrector and potentiator available as fixed-dose tablets and indicated for patients aged 12 years and older with at least one copy of F408del mutation. The phase III AURORA F/MF study observed a 13.8% mean improvement in FEV1 from baseline to week four (P<0.0001), and the phase III AURORA F/F study observed a 10% mean improvement in FEV1 from baseline to week four (P<0.0001).

Dr. Stephan discussed the multidisciplinary care team that is needed to treat patients, with nurses, dieticians, physicians, social workers, respiratory therapists, and program coordinators all required team members, while physical therapists, psychologists, research coordinators, and pharmacists are key recommended members. The team can help educate patients on medication-related concerns and directions, educate community pharmacists, recommend treatment adjustments, track treatment adherence, help overcome access issues, and navigate drug interactions.

She gave some tips for patient education and counseling of the various treatment options. Pancreatic enzymes should be taken immediately before eating and are needed for absorption of fat, protein, and carbohydrates. Patients should monitor for changes in stool, abdominal pain and bloating, oral mucosa irritation, and hyperuricemia while taking pancreatic enzymes. Fat-soluble vitamins should not be substituted and should be administered with food and pancreatic enzymes.

When counseling patients, there are several issues to communicate. For inhaled medication, wash hands before use and breathe in through the mouth, not the nose. Ensure patients understand the mechanism of action of these agents. CFTR modulators should be administered with a high-fat meal or snack and taken with pancreatic enzymes if the patient is pancreatic insufficient. Avoid eating grapefruit and Seville orange products when on these agents. Patients should check with the CF team before starting or stopping medications or supplements. Liver function tests should be monitored at baseline and every three months during the first year of treatment, and ophthalmologic examinations should be conducted in patients aged younger than 18 years.

Barriers to treatment adherence include prior authorization, pharmacy lock-in, limited distribution, need for mail-order delivery, and cost. Pharmacists are essential for ensuring proper medication use in patients with CF. “The pharmacist also tries to elicit patient-identified reasons for adherence issues to help us determine if a care plan is needed,” said Dr. Stephan. “Making sure our patients know what each medication is for and what it is helping them do is an essential part of improving adherence.” Patient counseling and assistance with medication access can reduce treatment burden and strengthen the pharmacist-patient relationship, she said.

Presentation: Comprehensive Cystic Fibrosis Management: A Review for Specialty Pharmacists. Asembia 2020 Specialty Pharmacy Summit Virtual Experience, May 19, 2020.