Outcomes

Remission

Remission is the best possible outcome in rheumatoid arthritis (RA). It can be considered the clinical state the patient was in before the onset of RA. Remission can be defined as either remission achieved while on treatment or remission off all therapy. Although spontaneous remission has often been quoted to occur in up to 15% of patients, it may be higher in patients with new-onset disease and far lower in those with years of well-established disease. Moreover, the rate of remission is dependent upon how it is defined, since American College of Rheumatology (ACR) remission criteria, disease activity score remission and radiographic remission definitions may yield very different outcomes.

Many observational studies have shown that about 30% of patients with ‘clinically suspect arthralgia’ (see Preclinical RA) and early disease (<3 months disease duration) will evolve into RA. Of note, <15% of patients with real RA will go into spontaneous remission. The factors that appear to favorably influence remission rates in patients with early RA include:

• Seronegativity
• Involvement of fewer numbers of swollen joints
• Shorter duration of symptoms.

The probability of remission in RA also is likely influenced by factors such as genotype, environmental factors (e.g., smoking), baseline comorbidities (e.g., obesity), the timing of diagnosis and the institution of disease-modifying antirheumatic drug (DMARD) therapy, the clinical care setting and socioeconomic factors such as educational status. Observational studies have shown that remission achieved on treatment is currently possible in 20% to 50% of RA patients under the following conditions:

• Earliest possible diagnosis
• Early, aggressive use of methotrexate (MTX), combination DMARDs, or biologic agents
• Avoidance of smoking, especially in those who are cyclic citrullinated peptide (CCP)–positive
• Clinical care dictated by a tight-control strategy (i.e., intensive, goal oriented, metric-based care).

Disability and Cost of Disease

RA can be a disabling and costly disease to the patient and to society. The annual total direct medical cost of RA in the United States per patient was estimated in 2018 at $12,509 ($3,723 in RA-specific costs) for all RA patients and $36,053 for biological DMARD users ($20,262 in RA-specific costs). The number of mean annual visits per RA patient in the United States has been estimated at 5.25 (for rheumatologist visits) and 4.8 (for non-rheumatologist visits), translating to a total of >10 million office visits per annum. In 2014, the number of hospitalizations for patients with RA was just under 500,000; however, the number of hospitalizations with a primary diagnosis of RA was 7350 in that year, with a downward trend since the year 2000, which saw 15,424 hospitalizations with RA as a primary diagnosis. Indirect costs, largely attributable to absenteeism and work disability, are difficult to quantify but have been estimated to contribute substantially to the total burden of RA, up to $22,444 per year. Moreover, having RA reduces lifetime earnings by 50% to 63%. After 8 to 11 years of disease, 43% to 85% are no longer able to work. Disability has not only been linked to the cost of disease, but also to excess mortality.

Prognostic Factors

The course of rheumatoid inflammation varies among individual patients but has been clearly shown to be influenced by numerous factors, including age at onset, educational level, socioeconomic status, lag time from onset symptom to diagnosis and from onset to DMARD initiation, the number of swollen joints, sustained elevations of acute-phase proteins, the presence of RA-related autoantibodies (e.g. RF, CCP antibodies, etc.), the presence of radiographic erosions, genetic background, degree of disability in the first year, comorbidities and access to care. Table 3-1 displays the evidence-based predictors of poor outcomes (and mortality) in RA.

Since many of these predictive factors are constitutive or unavoidable, the clinician must focus on those modifiable factors that may alter the course of disease and ultimate outcome. Of these, the most important is the timing of diagnosis and DMARD initiation. Hence early diagnosis and aggressive treatment of RA strongly depend on the clinician to ensure the best possible outcomes.

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Measuring Outcomes in RA

Studies have shown the added value of regularly assessed RA activity measurements on outcomes. The Tight Control of RA (TICORA) trial was an 18-month study of 110 early RA patients who were randomized to receive routine rheumatologic care (visits every 3 months) or intensive care. The intensive or tight-control group was evaluated monthly, using the disease activity score (DAS) to guide proscribed treatment changes if the patient failed to meet criteria for remission (DAS <2.4). The tight-control group had far more remissions (65% vs 16%) and ACR70 responses (71% vs 18%), greater functional improvement and less radiographic damage. Despite the use of similar DMARD regimens, patients treated in this goal-oriented manner (tight-control group), using validated outcome measures, were four times more likely to achieve remission or near remission (ACR70). A variety of clinical trial and clinical practice disease activity measures have been developed and are essential in the implementation of the treat-to-target strategy. The ACR has endorsed a number of these, including Clinical Disease Activity Index (CDAI), Disease Activity Score with 28-joint counts (DAS28) erythrocyte sedimentation rate (DAS28-ESR) or CRP level (DAS28-CRP), Patient Activity Score II (PAS-II), Routine Assessment of Patient Activity Index (RAPID3) and Simplified Disease Activity Index (SDAI). The most important are discussed in more detail in Preclinical Rheumatoid Arthritis.