Inclusion Criteria:

• Age 18–65 years at enrollment.

• Ability to understand study procedures and provide written informed consent.

• Willingness and ability to complete baseline questionnaires, QST, MRI/fMRI, and blood collection, unless a specific procedure is omitted for safety, operational, or participant-preference reasons.

• Ability to comply with study procedures in English, unless validated instruments and consent processes are available in another language under IRB-approved procedures.

PIRRA and NIRRA Inclusion Criteria:

• Fulfillment of 2010 ACR/EULAR classification criteria for RA.

• Fulfillment of 2021 EULAR criteria for D2T-RA, including:

  • Failure of at least two biologic or targeted synthetic DMARDS with different mechanisms of action after prior csDMARD failure or contraindication;

  • Evidence of ongoing disease burden;

  • Perceived management difficulty by the rheumatologist and/or patient.

• Clinically meaningful persistent RA-related joint/periarticular musculoskeletal pain, defined as:

  • Average RA-related pain >3/10 over the past 4 weeks; and

  • Similar RA-related pain present for at least 3 months.

• RA-related joint/periarticular pain judged by the study rheumatologist to be a clinically meaningful contributor to the participant’s current pain.

• Completion of ARTHUR ultrasound and, when trigger criteria are met, targeted non-ARTHUR ultrasound before final PIRRA/NIRRA classification.

RA-LDA Inclusion Criteria:

• Fulfillment of 2010 ACR/EULAR classification criteria for RA.

• Current low disease activity or remission defined by CDAI ≤10.

• Current and average past 4-week RA-related joint/periarticular pain ≤3/10.

• Does not meet 2016 ACR fibromyalgia criteria.

• No definite active ultrasound synovitis or tenosynovitis by the study ultrasound definition.

RA+FM Inclusion Criteria:

• Fulfillment of 2010 ACR/EULAR classification criteria for RA.

• Fulfillment of 2016 ACR fibromyalgia criteria at enrollment.

• Does not meet all enrollment criteria for PIRRA or NIRRA.

• Age 18–65 years.

• Ability to complete baseline study procedures.

Healthy Control Inclusion Criteria:

• Age 18–65 years.

• No diagnosis of RA.

• No systemic autoimmune or inflammatory rheumatic disease.

• No fibromyalgia.

• No chronic pain disorder.

• No persistent or recurrent pain lasting ≥3 months by screening history or Michigan Body Map (15).

• No clinically meaningful current musculoskeletal pain.

• No chronic immunosuppressive therapy.

• Eligible to complete MRI and QST procedures.

Exclusion Criteria:

• Contraindication to MRI, including non-removable MRI-incompatible implants or devices.

• Severe claustrophobia preventing MRI completion.

• Body habitus or weight exceeding MRI scanner safety or table limits.

• Inability to lie safely and comfortably for MRI because of severe pain, advanced kyphosis, or other positioning limitation.

• Known moderate-to-severe neurologic disease or structural brain abnormality likely to compromise interpretation of MRI outcomes, including clinically significant stroke, demyelinating disease, brain tumor, moderate-to-severe traumatic brain injury, neurodegenerative disease, uncontrolled seizure disorder, or moderate-to-severe white matter/vascular brain disease.

• Unstable or severe psychiatric illness that compromises participant safety, informed consent capacity, ability to complete study procedures, or validity of QST/MRI data. Examples include active suicidal ideation with intent or plan, current psychosis, acute mania, severe behavioral instability, or severe anxiety/claustrophobia preventing MRI completion.

• Active substance use disorder or intoxication/sedation at the time of study procedures that compromises safety, informed consent capacity, or data validity.

• Acute infection, recent surgery, hospitalization, or unstable medical condition that, in the judgment of the investigator, would compromise participant safety or study data validity.

• Use of an investigational drug or investigational device within the prior 3 months, unless approved by the PI as not relevant to study outcomes.

• Any other condition that, in the judgment of the investigator, would make study participation unsafe or compromise study integrity.

RA Group-Specific Exclusion Criteria:

• Confirmed diagnosis of another systemic autoimmune or inflammatory rheumatic disease judged to confound RA classification or pain phenotype, such as psoriatic arthritis, axial spondyloarthritis, systemic lupus erythematosus, systemic sclerosis, inflammatory myopathy, or systemic vasculitis.

• Use of investigational drugs for RA within the past 3 months.

• Clinically meaningful pain primarily attributable to a clearly unrelated non-RA pain condition when the participant does not meet RA+FM criteria and does not report clinically meaningful RA-related joint/periarticular pain. Examples include isolated mechanical low back pain, lumbar stenosis, neuropathy, injury-related pain, headache disorder, or osteoarthritis unrelated to RA as the dominant pain driver.

Healthy Control Exclusion Criteria:

• RA or history of inflammatory arthritis.

• Systemic autoimmune or inflammatory rheumatic disease.

• Fibromyalgia or chronic widespread pain.

• Chronic pain disorder.

• Persistent or recurrent pain lasting ≥3 months by screening history or Michigan Body Map.

• Clinically meaningful current musculoskeletal pain.

• Current use of immunosuppressive therapy.

• Current use of chronic opioid therapy or centrally acting pain medication for chronic pain.

• Moderate-to-severe neurologic or structural brain disease likely to affect MRI interpretation.

• Any general exclusion criterion listed above.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 09/29/2026. Questions regarding updates should be directed to the study team contact.