D1.58 - Pilocarpine in the management of allergic rhinosinusitis; a prospective, placebo-controlled study for a novel use of a cholinergic agent

Allergic rhinosinusitis (ARS) is treated with pharmacological, surgical and immunotherapy means. In spite of progresses in treatment, obstructive symptoms are often recalcitrant and frustrating. This study addresses the relevance of impaired cholinergic activity in ARS with prominent sino-nasal blockage.

Pilocarpine, a muscarinic-receptor agonist, was administered, in addition to ongoing chronic treatment, to patients with refractory symptoms to enhance cholinergic activity. The primary aim was improved secretion and clearance of the sino-nasal cavities by means of increased motor-neuron activity and, possibly, by heightened sensory input.  

Subjects with ARS were randomized to treatment with pilocarpine 5 mg tid versus placebo tid. The 22-item sino-nasal outcome test (SNOT-22) was used to identify subjects with symptoms recalcitrant to standard treatment. 

Because of adverse events associated with pilocarpine, dosing was adjusted at 4 weeks of treatment to bid or qd administration of 5 mg of pilocarpine if necessary. The 22-item sino-nasal outcome test (SNOT-22) was administered at the beginning of the study, 3 months, and 6 months of treatment. At 6 months of treatment, pilocarpine was discontinued. At 12 months of study the SNOT-22 questionnaire was administered again to assess the sustainability of the pilocarpine effect.

Thirty-seven subjects were randomized, with 19 receiving pilocarpine. Two subjects of the pilocarpine-treated group discontinued therapy due to adverse effects. Eight subjects required adjustment of their daily-dose pilocarpine. SNOT-22 scores were lower in the pilocarpine treated group at 6 months of treatment and at 6 months after discontinuation of pilocarpine (p-value < 0.01 and < 0.1 respectively).

Higher dosing appeared more effective as SNOT-22 scores were significantly lower in the pilocarpine tid-treated group, both at 6 months of treatment and at 6 months after discontinuation (p-value < 0.05 and < 0.001 respectively). In subjects with lowered pilocarpine dosing (qd or bid), significance was reached at p-value < 0.1 for subjects who took pilocarpine once a day, but was not observed at 6 months of discontinuation. 

Pilocarpine can prove a useful adjunct to the treatment of refractory ARS with sino-nasal blockage. Adverse effects are frequent but for most patients tolerable at dose of 5 mg tid. Lower dosing is also effective. Therapeutic benefit appears sustained upon discontinuation.