Repository Corticotropin Injection (Acthar® Gel) for Refractory Severe Noninfectious Keratitis: Efficacy and Safety from a Phase 4, Multicenter, Open-Label Study

Abstract

Introduction: Noninfectious keratitis is a painful corneal inflammation treated with topical cyclosporine and other immunosuppressants. Additional treatment options are needed for keratitis that does not improve with standard therapies. Repository corticotropin injection (RCI; Acthar Ò Gel) is approved to treat severe acute and chronic allergic and inflammatory processes involving the eye and its adnexa, including keratitis. This phase 4, multicenter, open-label study assessed the efficacy and safety of RCI for refractory severe noninfectious keratitis. Methods: Patients were C 18 years old with persistent severe keratitis despite treatment with topical immunosuppressants. Patients received 80 U of RCI subcutaneously twice weekly for

Pain and Fatigue Improvements in Patients Treated with Repository Corticotropin Injection Across Five Indications: A Narrative Review

“…PRO tools used in the studies summarized in this report include the functional assessment of chronic illness therapy-fatigue (FACIT-F) [ 11 , 12 ]; the lupus quality of life (LupusQOL) instrument, which includes pain-specific and fatigue-specific domains [ 25 ]; the fatigue assessment scale (FAS) [ 15 ]; patient assessment of pain by VAS (VAS pain) [ 22 , 26 ]; and for uveitis and keratitis, the ocular discomfort score (ODS) [ 16 ]; four-symptom questionnaire (assessing dryness, grittiness, burning, stinging) [ 16 ]; and eye-specific VAS measures (assessing eye dryness, burning/stinging, itching, foreign body sensation, eye discomfort, photophobia, pain) [ 16 ]. Burning and stinging may be considered indicators of pain in patients with keratitis.…”

“…Two studies included findings on PRO and/or physician-reported pain or fatigue measures in patients with uveitis or noninfectious keratitis (Table 3 ) [ 16 , 22 ]. In a retrospective chart review of 91 patients with uveitis treated in the previous 12 months, Nelson et al [ 22 ] reported data on physicians’ assessments of patient’s current status after RCI injection and type of observed improvements, including improvements in pain.…”

“…Please select outcomes that have improved as a result of RCI treatment) No. of patients: N = 91 Inclusion: Diagnosis of uveitis; received RCI in past 12 mo; completed course of RCI or receiving RCI at time of collection; complete medical records available Exclusion: Infectious eye inflammation; ophthalmic neoplasm; recent ophthalmic or orbital surgery (within 60 before diagnosis); recent eye trauma (within 60 days before diagnosis) Mean ± SD age 41 ± 14 years Gender: female (62%); male (38%) Uveitis symptoms, % patients: Blurred vision (89%); light sensitivity (45%); floaters (44%); visual loss/acuity (44%); eye pain (37%); eye redness (33%) None Physicians’ impressions of therapeutic response after RCI injection (% patients): Patient’s current status: Improved (84%); same (15%); worsened (0) Outcomes that had improved as a result of RCI treatment: Improvements in pain (27%) Noninfectious keratitis Wirta et al, 2021 [ 16 ] Objective: To evaluate the efficacy and safety of RCI for the treatment of refractory severe noninfectious keratitis that had not adequately responded to treatment with standard-of-care therapies Design: Prospective open-label phase 4 trial Treatment: RCI 80 U SC twice weekly for 12 weeks, then tapering for 4 weeks (RCI reduced to 40 U twice weekly for 2 weeks, then 40 U once weekly for 2 weeks) Primary endpoint: Proportion of patients with ≥ 12-point improvement in symptom bother domain of IDEEL questionnaire at week 12 and proportion of patients with ≥ 20%, 30%, and 50% improvement in symptom bother domain of IDEEL questionnaire at week 12 Fatigue and/or pain outcome(s) : Patient-reported VAS pain item; burning and stinging items of the 4-symptom questionnaire No. of patients: N = 35 Inclusion: Age ≥ 18 years; normal lid anatomy; history of severe keratitis in 1 or both eyes and history of previous treatment for keratitis within previous 6 months; no symptomatic improvement or did not tolerate previous treatment with topical cyclosporine or lifitegrast; in ≥ 1 eye at screening and baseline have all of the following: inferior corneal fluorescein staining score ≥ 2 in any field, corneal sum fluorescein staining score ≥ 4, conjunctival sum lissamine green staining score ≥ 2, conjunctival redness score ± 1, Schirmer score ≥ 1 mm/5 min and ≤ 10 mm/5 min, and ODS ≥ 2 Exclusion: Any ocular condition that, according to investigator’s opinion, could affect study parameters; history of LASIK or other ocular surgical procedure within 12 months of baseline visit; ocular trauma, penetrating intraocular surgery, refractive surgery, corneal transplantation, or eyelid surgery within 12 weeks before screening visit; any scheduled ocular surgical procedure during study; active or history of ocular herpes or other ocular infection within 30 days of prior baseline visit; have current punctal plugs, punctal occlusion, or history of nasolacrimal duct obstruction; unwillingness to avoid wearing contacts for 7 days before screening visit and for duration of study Mean ± SD age 63 ± 10 years Sex: female (71%); male (29%) ...…”

“…RCI is approved by the US Food and Drug Administration (FDA) for use in 19 indications, including for the treatment of selected patients with RA, SLE, keratitis, uveitis, and symptomatic sarcoidosis [ 8 ]. Results from several clinical trials support the use of RCI as treatment for patients with RA, SLE, sarcoidosis, and noninfectious keratitis [ 9 – 16 ]. A prospective, single-group open-label study of RCI in eight patients with refractory RA reported statistically significant improvements in the primary endpoints of Ritchie–Camp articular index tender joint count and swollen joint count and in the total disease activity score for RA (DAS28) at 12 weeks; patient and physician global visual analog scales (VASs) also showed significant improvement at 12 weeks [ 9 ].…”

“…Similarly, a randomized comparison of two RCI doses in patients with chronic pulmonary sarcoidosis who were receiving prednisone found significant decreases from baseline in prednisone dosage and improvements in pulmonary function, chest imaging, health-related quality of life, and fatigue for the 16 patients who persisted with 24 weeks of RCI treatment [ 15 ]. A prospective, open-label, single-arm phase 4 trial in patients with noninfectious keratitis reported that at week 12 of RCI therapy, 50% of patients had clinically important improvements in the primary endpoint, which was defined as the proportion of patients with at least a 12-point improvement in the symptom bother domain of the Impact of Dry Eye on Everyday Life (IDEEL) questionnaire at week 12 [ 16 ].…”