The Earlier the Better in Treating Undifferentiated Arthritis


Early intervention may prevent or delay the development of RA.

Key points
• Treating undifferentiated arthritis early delays the development of rheumatoid arthritis (RA) by up to a year.

• Methotrexate appears to be the drug of choice for early treatment of undifferentiated arthritis.

• Intramuscular methylprednisolone can be used if methotrexate is contraindicated.

• Other treatments may delay progression of undifferentiated arthritis, but their effect was not significant.

Arthritis that does not completely meet the diagnostic criteria for RA is considered undifferentiated and may have a diverse presentation. Maria Lopez-Olivo and colleagues1 at the University of Texas in Houston point out that undifferentiated arthritis may often be an early presentation of a defined arthritis and may offer an opportunity for early treatment.

The presence of rheumatoid factor and the HLA-DRB1 allele may be clues to the development of RA from an undifferentiated presentation. Further evidence suggests that some patient characteristics such as older age, arthritis of the hands, and high disease activity in undifferentiated arthritis may predict progression to RA.

The authors sought to determine whether any treatments used for undifferentiated arthritis prevented or delayed progression to RA. They recently presented their findings in Arthritis Care & Research.

The study
The authors conducted a systematic review and meta-analysis that looked at proportions of patients in whom RA developed during the study period. Secondary outcomes included remission, disease activity scores in 28 joints, joint damage progression, synovitis, and changes in core variables for RA. Ultimately, 9 trials were included in the analysis.

The results
• Patients treated with any type of intervention were less likely to develop RA at 12 months (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.26-0.90).

• Looking at each individual treatment, only methotrexate led to a statistically significant delay in progression to RA (OR, 0.13; 95% CI, 0.03-0.48).

• 19% of patients who received methotrexate developed RA compared with 59% of controls.

• No differences were seen at 30 and 60 months (OR, 0.60; 95% CI, 0.28-1.3, and OR, 0.75; 95% CI, 0.35-1.6, respectively).

• An insignificant trend toward delayed progression was observed in those who received intramuscular methylprednisolone: 47% diagnosed with RA at 12 months versus 55% of controls (OR, 0.72; 95% CI, 0.51-1.0).

• The odds ratios of the respective treatments leading to RA at 12 months are: methotrexate (OR, 0.16; 95% CI, 0.08-0.33), abatacept (OR, 0.56; 95% CI, 0.20-1.6), intra-articular methylprednisolone (OR, 0.57; 95% CI, 0.09-3.7), intramuscular methylprednisolone (OR, 0.72; 95% CI, 0.53-0.99), and infliximab (OR, 2.0; 95% CI, 0.49-8.2).

• All interventions improved at least one secondary outcome.

Implications for physicians
• When a patient presents with undifferentiated arthritis, start treatment early as doing so may postpone progression to RA.

• Treatment with methotrexate is most likely to prevent the progression of undifferentiated arthritis to RA at 1 year with intramuscular methylprednisolone as a second option.

• Early treatment with any therapy described above may lead to lower disease activity, improved remission, less swollen and tender joints, less synovitis, lower fatigue, and/or less radiographic progression of joint damage.

• Patients with anti-CCP antibodies may deserve special consideration as disease progression may be more rapid.


No funding was reported.


1. Lopez-Olivo MA, Kakpovbia-Eshareturi V, des Bordes J, et al. Treating early undifferentiated arthritis: a systematic review and meta-analysis of direct and indirect trial evidence. Arthritis Care Res. 2017 Nov 21. doi: 10.1002/acr.23474. [Epub ahead of print]

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