Adalimumab

Drug-combination studies

Double-blind, placebo-controlled comparisons of adalimumab alone or combined with disease-modifying antirheumatic drugs showed no significant differences in the incidence of serious adverse effects and infections, but more frequent injection-site reactions with adalimumab [ ].

Placebo-controlled studies

In a multicenter, randomized, double-blind, placebo-controlled study of subcutaneous adalimumab 40 mg every other week for 24 weeks, those who received adalimumab reported more adverse events (75% versus 60%), but there was no statistically significant difference in the incidence of infections; most adverse events were mild or moderate in intensity [ ].

Respiratory

Bronchospasm has been attributed to adalimumab [ ].

• A 48-year-old man with rheumatoid arthritis was treated with infliximab and etanercept without any serious adverse events; however, when he received adalimumab for the second time he developed severe bronchospasm.

Pulmonary granulomas with caseating necrosis, but no evidence of mycobacteria or other infectious agents, were attributed to adalimumab in a 73-year-old man [ ]. That pulmonary lesions persisted for more than 1 year after withdrawal made interpretation difficult.

Adalimumab-associated pulmonary fibrosis can occur in patients with rheumatoid arthritis.

• A 67-year-old man with rheumatoid arthritis developed a non-productive cough and progressive dyspnea after being given subcutaneous adalimumab 40 mg every 2 weeks for 2 months. A CT scan showed extensive pulmonary fibrosis, with ground-glass lesions, honeycombing, and traction atelectasis. The dose of prednisone was increased to 90 mg/day, antibiotics were withdrawn, and 2 months later he was discharged in satisfactory condition [ ].

• A 76-year-old woman with severe rheumatoid arthritis and no respiratory symptoms was given adalimumab instead of sulfasalazine and hydroxychloroquine. There was marked symptomatic improvement in her arthritis, but within 2.5 months she developed progressive shortness of breath. A CT scan showed extensive confluent reticular and honeycomb shadowing basally and posteriorly. Methotrexate and adalimumab were both withdrawn and she was given oral prednisolone. Her symptoms improved and she was discharged to receive home oxygen therapy [ ].

A patient receiving adalimumab developed fatal exacerbation of fibrosing alveolitis associated with systemic sclerosis [ ].

• A 74-year-old woman with severe Raynaud’s syndrome, sclerodactyly, pulmonary fibrosis, abnormal esophageal peristalsis, and severe polyarthritis taking azathioprine was given adalimumab. After 7 months she developed respiratory failure and fever (39.3 °C). A CT scan angiogram showed lesions with extensive ground glass opacities. She was treated with oxygen, diuretics, azithromycin, and methylprednisolone 1 g/day for 3 days, followed by prednisone 1 mg/kg/day and azathioprine. Adalimumab was withdrawn, but 3 months later her pulmonary function worsened and she died 2 months later from respiratory distress without infection.

Ear, nose, throat

Within a few weeks of starting adalimumab four patients with chronic rheumatoid arthritis developed newly diagnosed recurring sinusitis refractory to standard treatment, which resolved after adalimumab was withdrawn [ ].