Table 1 Recommendations for individuals receiving pegvaliase therapy and strength of recommendations
Recommendations | Strength of evidence |
|---|---|
1. Initiating a pegvaliase response trial | |
1.1 Include a metabolic dietitian and a metabolic physician or nurse practitioner, at a minimum, on the clinical team to manage individuals with PKU on pegvaliase therapy. Also consider including a psychologist, social worker, nurse, diet technician and clinic coordinator | Consensus |
1.2 Consider offering pegvaliase as a treatment option for adults with blood PHE > 600 µmol/L (including women who are not planning a pregnancy in the next year), adults on sapropterin therapy, adults with blood PHE < 600 µmol/L who want to achieve a normalized or unrestricted diet, and adults with neurocognitive deficits (including late-treated individuals; see also special populations) | Fair |
1.3 For individuals considering pegvaliase therapy, review the possibility of adverse events (AE) during treatment, as well as AE management, including Risk Evaluation and Mitigation Strategies (REMS) | Strong |
1.4. Discuss the clinic’s expectations for the individual initiating therapy including: the clinic’s protocol (visits, blood monitoring, communication, reasons for discontinuation) and typical course (time to response, dose and number of injections, and diet adjustments) | Fair |
1.5 In coordination with the medical team, consider pre-medications (including H1 and H2 receptor antagonists) prior to injections and/or with dose increases to manage or prevent adverse events | Fair |
1.6 Initiate and titrate pegvaliase injections as described in the prescribing information and make dose adjustments based on clinical judgement of individual tolerance and blood PHE response | Strong |
1.7 Provide weekly individual-clinic contact (via phone, email, in-person or telehealth) to assess therapy tolerance and provide support. Monitor medical and nutrition progress every 2–4 months during therapy initiation and titration | Consensus |
2. Recommendations for assessing and monitoring nutritional status during all phases of pegvaliase therapy | |
2.1 Establish at the clinic level standard repeatable methods for nutrition assessment and for assessing food attitudes, aversions, and fears related to normalizing a PHE-restricted diet. Conduct a comprehensive nutrition assessment at baseline, including dietary intake and typical eating patterns (using diet records, 24-h recall, food frequency questionnaires), with particular attention to protein adequacy [quantity, quality, and source of protein (plant, animal, synthetic)], and transition from medical food. Continue to evaluate the nutritional adequacy of dietary intake throughout treatment and recommend modifications and/or supplementation as needed | Fair |
2.2 Assess the individual’s dietary goals, food behavior and beliefs, and knowledge of what constitutes an unrestricted healthy diet. Include assessment of taste or texture aversions, fears and phobias of previously forbidden foods, and preferences for new foods to include as the diet is normalized | Weak |
2.3 Establish at the clinic level standard repeatable methods for assessing quality of life and neurocognitive assessment | Weak |
2.4 Monitor blood PHE and TYR concentrations every 1–4 weeks during initiation of pegvaliase therapy. Monitor with increased frequency during dose titration (some individuals may respond before the recommended titration schedule is completed) and diet adjustment periods, and during periods of hypoPHE (< 30 µmol/L) | Fair |
2.5 Monitor nutritional status biomarkers including: plasma amino acids, prealbumin, ferritin, vitamin D, and CBC at baseline and every 6–12 months (as recommended in the GMDI Nutrition Management for PKU Guideline). If dietary intake is suboptimal, or other indications of poor nutritional status are present, consider monitoring additional biomarkers including but not limited to vitamin B12, MMA, RBC folate, EFA, Fe, Zn, Se, lipid profile and Hgb A1c | Weak |
2.6 Review information pertinent to nutritional status in the medical history and physical exam. Assess physical signs of nutritional status at baseline and throughout therapy. Monitor vital signs and AEs weekly until week 24 and monthly thereafter with attention to vital signs prior to injection and for one hour post injection | Fair |
3. Recommendations for managing pegvaliase therapy after a response | |
3.1 Aim for a blood PHE concentration below 360 µmol/L and above 30 µmol/L | Fair |
3.2 Consider any clinically meaningful reduction in blood PHE concentration (as determined by the clinic) to be a positive outcome | Consensus |
3.3 For individuals receiving sapropterin therapy, continue sapropterin until blood PHE is in the treatment range (as defined by the clinic) and then discontinue | Fair |
3.4 Add protein in 10–20 g increments when blood PHE concentration falls to 120 μmol/L on two or more consecutive measurements and consider adding protein earlier if blood PHE levels are dropping rapidly. Continue adding intact protein incrementally until the DRI (0.8 g/kg for adults) is met or exceeded (by up to 1.5–2.0 times DRI), considering individual needs and preferences | Fair |
3.5 If blood PHE concentrations fall to < 30 µmol/L on two or more consecutive measurements, increase intact protein to meet the DRI or greater. If blood PHE remains below 30 µmol/L after increasing protein intake to at least the DRI, decrease total weekly pegvaliase dose | Fair |
3.6 Aim to eliminate medical food by decreasing incrementally as intact protein is increased | Fair |
3.7 If post-prandial blood TYR concentrations repeatedly fall below 30 µmol/L, consider increasing intact protein or providing TYR supplementation | Weak |
3.8 Aim for a positive therapy outcome that recognizes an individual’s preferences and goals. The goal of pegvaliase therapy is to maintain blood PHE control while consuming an unrestricted healthy diet with adequate intact protein and no medical food. A positive outcome is also achieved when individual preferences for degree of diet normalization, some continuation of medical food, and/or number of dose injections required for blood PHE control are taken into account | Weak |
4. Recommendations for educating and counseling regarding appropriate food choices to support normal nutrition requirements | |
4.1 Identify and address individual expectations and goals regarding benefits of pegvaliase therapy including normalization (containing at least DRI for protein and no medical food) or liberalization of diet while maintaining blood PHE control; and improving quality of life psychosocial well-being, and cognitive function. Continue to address expectations and goals as they change throughout therapy | Fair |
4.2 Provide ongoing education and counseling for transitioning to an unrestricted healthy diet including: addition of high protein foods, appropriate portion sizes, food safety, food purchasing and preparation, and weight management. Provide ongoing education and counseling for transitioning to an unrestricted diet | Weak |
4.3 Educate individuals who follow a predominantly vegetarian diet on how to incorporate adequate protein and micronutrients, including micronutrient supplements if necessary | Fair |
4.4 Recognize and provide counseling for individuals who have difficulty accepting foods that were previously not allowed, and refer to a psychologist or other professional, if indicated | Weak |
5. Recommendations for pegvaliase use in special populations | |
5.1 Counsel women of childbearing age about the limited information available on pegvaliase in pregnancy and the need for birth control to prevent unexpected pregnancies | Consensus |
5.2 For women receiving pegvaliase therapy, consider continuing pegvaliase during pregnancy, weighing the risks of the known teratogenic effects of high blood PHE on the fetus with the unknown risks of pegvaliase, and incorporating the woman's preferences | Consensus |
5.3 For women continuing pegvaliase therapy during pregnancy, aim for blood PHE concentration between 120 and 360 µmol/L and monitor blood PHE weekly to bi-weekly | Weak |
5.4 For women receiving pegvaliase who return to a PHE-restricted diet for pregnancy, discontinue pegvaliase at least 4Â weeks prior to a planned pregnancy | Fair |
5.5 For women who are returning to a PHE-restricted diet for pregnancy, provide frequent nutrition counseling and support | Weak |
5.6 Consider pegvaliase therapy during lactation with frequent monitoring of maternal blood PHE | Consensus |
5.7 Consider pegvaliase treatment for individuals aged 16Â years and older, taking into consideration level of blood PHE control, neurocognitive status, and quality of life on current therapy, as well as the individual's interest | Weak |