A Controlled Trial of Intermittent Fludarabine for Psoriatic Arthritis

Inclusion Criteria

• •Ability to provide informed consent to all aspects of the study after full information is provided.
• •Age equal to or older than 18 years.
• •Psoriatic arthritis of more than 6 months duration defined by the following criteria:
• •A psoriatic skin lesion (or history of psoriatic skin lesion documented by a physician) with or without nail involvement.
• •Peripheral arthritis alone or in combination with sacroiliitis. Patients with chest expansion less than 2.5 cm or decreased flexion of the cervical and lumbosacral spine flexion by 50% or more will be excluded.
• •A negative serum test for rheumatoid factor and absence of subcutaneous nodules.
• •Radiographic findings (if present) compatible with psoriatic arthritis ("pencil in cup lesion," osteolysis of the terminal phalanx, asymmetrical sacroiliitis, erosive oligoarticular arthritis or spinal syndesmophytes).
• •Criteria a-c are required for diagnosis whereas criterion d is optional.
• •Active arthritis with 3 or more painful or swollen joints considered capable of responding to drug therapy and at least 2 of the following:
• •Tenderness or pain on movement of at least 3 joints (or periarticular areas).
• •30 minutes of morning stiffness (in peripheral joints or in the spine).
• •Erythrocyte sedimentation rate (ESR) greater than or equal to 28mm/hour or C-reactive protein (CRP) greater than 0.8 mg/dl.
• •Failure to respond or development of intolerable side effects to at least one of the following treatments: sulfasalazine, gold retinoids, PUVA, methotrexate, azathioprine or cyclosporin. A waiting period of equal to or greater than 4 weeks after the end of previous systemic treatment will be required before initiation of fludarabine treatment. Topical treatment for psoriasis (glucocorticoids, tar, anthralin, etc.) should be discontinued 2 weeks prior to study entry.
• •not have seropositive, symmetric polyarthritis.
• •Must not have the spondylitic form of psoriatic arthritis (spondylitis alone or in combination with shoulder and hip arthritis).
• •Must not have arthritis mutilans.
• •Must not be receiving glucocorticoids in doses greater than 10mg/day of prednisone.
• •Patients must not have acute or chronic infections requiring antimicrobial therapy or serious viral (e.g., hepatitis, herpes zoster or HIV infections) or fungal infections. Patients with a positive PPD who have not received INH or other antituberculous therapy may be excluded if in the opinion of an infectious disease consultant immunosuppressive therapy is contraindicated.
• •Females must not be pregnant or lactating. Females of childbearing age must be practicing birth control.
• •No pre-existing malignancy other than basal cell carcinoma. All females must have a negative Papanicolaou smear within a 3 month period prior to study entry.
• •No history of cerebrovascular accidents, seizure disorder or chronic neurologic disease.
• •No history of documented coronary artery disease, cardiomyopathy or dysrhythmia requiring therapy.
• •No confounding medical illness that in the judgment of the investigators would pose added risk for study participants (e.g., chronic hepatic, renal or pulmonary disease (PFTs less than 70% of predicted value or DLCO less than 60%) or bone marrow hypoplasia (Hb less than 10 mg/dl, platelets less than 100.000/dl or WBC less than 3.400/dl).
• •No patients who have received alkylating agents for greater than or equal to 1 year.
• •No patients with creatinine clearance (CrCl) less than 50 ml/min.