Inclusion Criteria:
A. ≥18 years of age.B. Must fulfill McAdam's or Damiani's or Michet's Criteria Diagnostic Criteria for
Relapsing Polychondritis McAdam's Criteria (1976)
≥ 3 criteria out of 6 of the following:
1. Bilateral auricular chondritis. 2. Non-erosive seronegative polyarthritis. 3. Nasal chondritis. 4. Ocular inflammation. 5. Respiratory tract chondritis. 6. Cochlear and/or vestibular dysfunction.Damiani's Criteria (1979)
1. ≥3 of McAdam's Criteria as above. 2. ≥1 of McAdam's Criteria with histological confirmation of chondritis. 3. ≥2 of McAdam's Criteria with positive response to glucocorticoids or dapsone.Michet's Criteria (1986)
Presence of ≥2 of the following criteria:
1. Auricular chondritis. 2. Nasal chondritis. 3. Laryngotracheal chondritis.Or presence of ≥1 of the above criteria and ≥2 of the following criteria. 1. Seronegative inflammatory arthritis. 2. Ocular inflammation. 3. Hearing loss. 4. Vestibular dysfunction.C. Mild to moderately active disease within 60 days prior to screening where the symptoms
cannot be attributed to any cause other than RP and which, in the investigator's opinion,
requires addition/ increase in prednisone dose between 20-60 mg/ day.
At the time of enrollment and during the trial, the following symptoms of active disease
which will be evaluated:
1. Auricular inflammation: defined as increase/ new onset pain/ swelling/redness of
external ear(s), ear canal. 2. Nasal inflammation: defined as increase/ new onset pain/ swelling/redness of
external nose. 3. Ocular inflammation: defined as new onset/ worsening unilateral/ bilateral
episcleritis/scleritis/ uveitis.
4. Inflammatory arthritis: defined as new onset/ worsening morning stiffness≥30
minutes, physician diagnosed tenderness/swelling in ≥1 joint; new onset/ worsening
costochondritis.
5. Mild to moderate airway inflammation: defined as new onset/ worsening mild to
moderate inflammation of upper airway diagnosed by direct laryngoscopy and
attributed to RP; abnormal CT airway/ bronchoscopy showing wall thickening of airway
(larynx, trachea, bronchi) and absence of severe manifestations such as new onset
SGS/tracheomalacia/ bronchomalacia.
6. Sinonasal disease: defined as new onset/ increase in nasal crusting, discharge
bleeding. 7. Constitutional symptoms: defined as new onset/ worsening fever, unintentional weight
loss of ≥ 5% of body weight, night sweats Patients must have at least 1 of the first
5 criteria within the past 60 days prior to the enrollment.
D. Willing and able to comply with treatment and follow-up procedures.
E. Both men and women of childbearing potential must be willing to use an effective means
of birth control while receiving treatment throughout the study. Effective contraception
methods include abstinence, oral contraceptives (birth control pills),
intra-uterine-device, diaphragm, approved hormone injections, condoms, or medical
sterilization.
F. Willing and able to provide written informed consent.
Exclusion Criteria:
A. Severe disease manifestations within the past 28 days, including:
1. Severe airway inflammation with supplemental oxygen requirement, tracheostomy,
airway stenting, ventilation. Patients with prior history of severe airway disease,
who currently have damage will be eligible if they have mild- moderate active
disease within the past 60 days at the time of enrollment.
2. Central nervous system (CNS) disease (meningitis, encephalitis, optic neuritis)
requiring hospitalization/ treatment with intravenous methylprednisolone/
cyclophosphamide.
3. Cardiac disease (symptomatic valve dysfunction, heart failure) requiring active
treatment for heart failure/ hospitalization/ consideration for surgery.
4. Severe ophthalmologic manifestations: severe scleritis, uveitis, retinal vasculitis,
optic neuritis which is imminently vision threatening.
5. Any disease manifestation considered organ/ life-threatening felt to require
treatment with prednisone>60 mg/ day or IV methylprednisolone or cyclophosphamide.
B. Patients with current/ prior use of methotrexate or azathioprine will be eligible for
stage 1 or stage 2 of the study depending on the duration of treatment with the non-
biologic DMARD treatment.
C. Patients with exposure to biologic DMARDS will be excluded.
D. Evidence of active infection.
E. Known infection with human immunodeficiency virus (HIV), hepatitis C, or a positive
hepatitis B surface antigen.
F. Patients at risk for tuberculosis (TB) defined as follows:
1. Current clinical, radiographic or laboratory evidence of active TB, even if
currently being treated. Chest x-rays (posterior/anterior and lateral) obtained
within the 6 months prior to screening and TB testing (IFN gamma release assay or
PPD) performed in the past month prior to screening will be accepted; however, a
copy of the reports must be placed in the participant binder.
2. A history of active TB unless there is documentation that the patient had received
prior anti-TB treatment that was appropriate in duration and type according to local
health authority guidelines.
3. Patients with a positive TB screening test indicative of latent TB will not be
eligible for the study unless they: i. Have no evidence of current TB based on chest
x-ray performed during the screening period and by history and physical exam, and
ii. They are currently being treated for latent TB or the site has documentation of
successful prior treatment of latent TB. Treatment regimens should be dictated by
local guidelines as long as the treatment dose and duration meet or exceed local
health authority guidelines. Patients with latent TB may be eligible for the trial
prior to completion of treatment as long as they have completed at least 4 weeks of
treatment and they have no evidence of current TB on chest x-ray at screening.
G. Inability to comply with study guidelines.
H. Cytopenia: platelet count <80,000/mm3, absolute neutrophil count <1500/mm3, hematocrit
< 20%.
- I. Other uncontrolled disease (co-morbidity) that could prevent a subject from fulfilling
the study requirements or that would increase the risk of study procedures.
J. Patients who have a present malignancy or previous malignancy within the last 5 years
prior to screening (except documented history of cured non-metastatic squamous or basal
cell skin carcinoma or cervical carcinoma in situ). Patients who had a screening
procedure that is suspicious for malignancy, and in whom the possibility of malignancy
cannot be reasonably excluded following additional clinical, laboratory or other
diagnostic evaluations.
K. Receipt of an investigational agent or device within 30 days prior to enrollment.L. A live vaccination < 4 weeks before enrollment.M. Presence of any of the following diseases:
1. ANCA-associated vasculitis. 2. Polyarteritis nodosa. 3. Giant cell arteritis. 4. Takayasu's arteritis. 5. Cogan's syndrome. 6. Sarcoidosis. 7. Kawasaki disease. 8. Tuberculosis or atypical mycobacterial infections. 9. Deep fungal infections. 10. Lymphoma, lymphomatoid granulomatosis, or other type of malignancy that mimics
vasculitis. 11. Cryoglobulinemic vasculitis. 12. Systemic lupus erythematosus. 13. Rheumatoid arthritis. 14. Overlap with other autoimmune diseases. 15. Diagnosis of VEXAS syndrome
