What is the likely cause of a rheumatoid arthritis patient's sudden deterioration from 50% to 20% improvement, with worsening joint pain, after being on adalimumab (adalimumab, a tumor necrosis factor-alpha inhibitor) for over 6 months, with previous low Simplified Disease Activity Index (SDAI) score and Disease Activity Score in 28 joints (DAS28) score, is it loss of efficacy of adalimumab or a disease flare-up?

From the Guidelines

The patient should continue adalimumab while the cause of the symptom worsening is investigated, as it is more likely a flare-up rather than adalimumab failure. The patient had excellent disease control two months ago (SDAI 0.2 and DAS28 1.52, both indicating remission) after 6 months of successful adalimumab treatment. When a patient who has been responding well to a TNF inhibitor like adalimumab suddenly experiences worsening symptoms, several factors should be considered before concluding the medication has failed. These include intercurrent infection, medication non-adherence, stress, or a true autoimmune flare. Secondary failure of adalimumab typically occurs more gradually, not suddenly after documented remission, as stated in the EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update 1. I would recommend continuing adalimumab at the current dose while evaluating for infection (obtain CBC, inflammatory markers), assessing medication adherence, and considering a short course of prednisone (10-20mg daily for 5-7 days) to address the acute symptoms. If symptoms persist despite these interventions, then medication failure becomes more likely, and switching to another biologic agent would be appropriate, as suggested by the EULAR recommendations 1. Temporary symptom worsening in a previously well-controlled patient usually warrants investigation before changing an otherwise effective therapy. The use of validated composite measures of disease activity, such as DAS or DAS28, is also recommended to guide treatment decisions, as stated in the treating rheumatoid arthritis to target: recommendations of an international task force study 1. Additionally, the patient should be informed about the treatment target and the strategy planned to reach this target under the supervision of the rheumatologist, as emphasized in the EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update 1. The patient's disease activity and treatment response should be monitored frequently, and adjustments to the treatment plan should be made as needed to achieve and maintain the desired treatment target, as recommended by the EULAR guidelines 1.

From the FDA Drug Label

In Study RA-III, the mean (95% CI) improvement in HAQ-DI from baseline at week 52 was 0.60 (0.55,0.65) for the HUMIRA patients and 0.25 (0.17,0.33) for placebo/MTX (p<0.001) patients. Eighty-two percent of these patients maintained that improvement through week 104 and a similar proportion of patients maintained this response through week 260 (5 years) of open-label treatment.

The patient's recent decline in condition, from feeling 50% better to 20% better, with every joint aching, may be a flare-up. The fact that the patient was responding well to adalimumab for over 6 months, with recent scores of SDAI SCORE: 0.2 and DAS28 SCORE of 1.52, suggests that the medication was effective. However, the current symptoms could indicate a disease flare, which is a common occurrence in rheumatoid arthritis.

• The FDA label does not provide direct information on the specific scenario of a patient experiencing a decline in condition after initial response to adalimumab.
• It is essential to monitor the patient's condition closely and consider adjusting the treatment plan as needed 2.

From the Research

Possible Reasons for Decreased Efficacy of Adalimumab

• The patient's condition may be experiencing a flare-up, which is a common occurrence in rheumatoid arthritis patients, even those who have been responding well to treatment 3.
• It is also possible that the adalimumab is no longer effective for the patient, which can happen over time due to various factors such as the development of antibodies against the drug 4.
• The patient's disease activity may have changed, requiring an adjustment in treatment, such as adding or switching to a different medication 5, 6.

Factors to Consider

• The patient's recent scores of SDAI and DAS28 indicate a good response to adalimumab treatment, but the current decrease in efficacy may require a re-evaluation of the treatment plan 3.
• The patient's history of responding well to adalimumab suggests that the drug was effective in the past, but the current situation may require a different approach 4, 7.
• The possibility of a flare-up or decreased efficacy of adalimumab should be considered in the context of the patient's overall disease activity and treatment history 5, 6.

Next Steps

• A thorough evaluation of the patient's current condition and treatment history is necessary to determine the best course of action 3, 7.
• Consideration should be given to adjusting the treatment plan, such as adding or switching to a different medication, or exploring other treatment options 5, 6.
• The patient's response to adalimumab should be continuously monitored, and adjustments made as necessary to ensure optimal disease management 4, 7.