Perspective of Adults With Neurofibromatosis 1 and Cutaneous Neurofibromas: Implications for Clinical Trials

Abstract

Objective: To assess the perspectives of adults with neurofibromatosis 1 (NF1) regarding cutaneous neurofibroma (cNF) morbidity, treatment options, and acceptable risk-benefit ratio to facilitate the design of patient-centered clinical trials.

Methods: An online survey developed by multidisciplinary experts and patient representatives of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) cNF Working Group was distributed to adults with NF1 (n = 3,734) in the largest international database of individuals with any form of NF. Eligibility criteria included self-reported NF1 diagnosis, age ≥18 years, ≥1 cNF, and ability to read English.

Results: A total of 548 adults with NF1 responded to the survey. Respondents ranked appearance, number, and then location as the most bothersome features of raised cNF. Seventy-five percent of respondents considered a partial decrease of 33%-66% in the number or size of cNF as a meaningful response to experimental treatments. Most respondents (48%-58%) were willing to try available cNF treatments but were not aware of options outside of surgical removal. Regarding experimental agents, respondents favored topical, then oral medications. Most individuals (>65%) reported being "very much" or "extremely willing" to try experimental treatments, especially those with the highest cNF burden. Many respondents were not willing to tolerate side effects like nausea/vomiting (51%) and rash (46%). The greatest barriers to participation in cNF clinical trials were cost of participation and need to take time off work.

Conclusions: Most adults with NF1 are willing to consider experimental therapies for treatment of cNF. These data will guide the design of patient-centered clinical trials for adults with cNF.

Figure 1. Acceptable Cutaneous Neurofibroma (cNF) Treatment Response.

(A-B) Survey respondents were asked: “When thinking about the raised cutaneous neurofibromas that bother you the most, what is the minimum decrease in [number/size] that would be acceptable to you after participating in a treatment trial?” The questions were accompanied by baseline images and digitally manipulated into a series visually representing a 33%, 66%, and 100% decrease in cNF number and size. (A) Images used for cNF number decrease. (B) Graphical representation of the responses. (C) A 5-point Likert scale was utilized to assess agreement with the statements listed on the y axis.

Figure 2. Views Related to Specific Aspects of Cutaneous Neurofibromas (cNF).

5-point Likert scales were utilized for responses to the questions: (A) “How much does each FEATURE of your raised cNFs bother you (physically, cosmetically, or emotionally)?”; (B) “How much do your cNFs bother you on each AREA of your body (physically, cosmetically, or emotionally)?”

Figure 3. Willingness To Try Experimental Treatments and Risk Side Effects.

5-point Likert scale responses were utilized for the following questions: (A) “Assuming equal effectiveness and safety, what is your willingness to try these EXPERIMENTAL treatments for cutaneous neurofibromas?”; (B) “What side effects are you willing to risk for treatment of your cutaneous neurofibromas even if they may grow back later?”