Early treatment considerations in RA, April 2023

In evaluating the importance of early aggressive treatment of rheumatoid arthritis (RA), we often look at prognostic factors for severe disease, such as seropositivity, elevated inflammatory markers, and erosions. Eberhard and colleagues looked at the relationship between damage as seen on radiography (including erosions and joint space narrowing) and pain and disability in early RA using an inception cohort with <12 months of symptoms. Over 200 patients in Sweden were followed for 5 years with clinical, laboratory, and radiographic evaluations. Of interest, pain was associated with female sex, tender joint count, and inflammatory markers at various time points but not with radiographic damage. This may reflect that pain is related to current inflammation rather than past joint damage or that pain is related to other factors, such as central sensitization. Radiographic damage was, however, associated with disability and thus remains an important target and outcome measure for assessing treatment effectiveness.

Leon and colleagues also looked at early RA but instead, at the category of difficult-to-treat RA (D2T RA), meaning persistent RA symptoms after a trial of at least two biologic or targeted synthetic disease-modifying antirheumatic drugs. In order to gain better insight in preventing D2T RA, the authors examined its association with potentially modifiable risk factors early in the course of disease. Of the over 600 patients followed in this inception cohort, only about 6% were classified as having D2T RA. The study found that patients who had D2T RA tended to be younger, with a higher tender joint count, higher pain scores, and a higher initial level of disability. The Disease Activity Score (DAS28) itself was higher in patients with D2T RA, but the difference did not reach statistical significance. The small number of patients (35) in the D2T RA group may have affected the findings as well as their wider applicability. However, it is interesting to consider whether the associations may also reflect the impact of noninflammatory factors, as in the previous study, on the classification of D2T RA.

Park and colleagues evaluated the difference in clinical outcomes in postmenopausal patients with RA who underwent menopause at younger than 45 years or 45 years or older. Among over 2800 patients in Korea, those who underwent early menopause were more likely to be seronegative and have high disease activity and worse patient-reported outcome scores in fatigue, sleep, and health-related quality of life despite comparable treatments and prevalence of erosions. The authors suggest this may be related to lower cumulative estrogen exposure; whether this correlates to inflammatory cytokine signatures is not yet known. However, as with the prior studies, central sensitization and noninflammatory pain may also contribute and should be considered in interpreting response to therapy.

Finally, addressing the potential risk for cancer in patients with RA before or during treatment with immunosuppressive medications, Miyata and colleagues reported a study that screened nearly 2200 patients who underwent CT (from neck to pelvis) and compared them with those who underwent routine screening with physical exam plus radiography. The study found that CT screening enhanced cancer detection, with a large number of cancers detected at an earlier stage with CT screening compared with routine screening. The overall number of cancers detected was low (33), and thus routine screening with neck-to-pelvis CT for all patients with RA may not be a cost-effective practice. However, it bears further examination for potentially higher-risk populations or specific cancers.

In evaluating the importance of early aggressive treatment of rheumatoid arthritis (RA), we often look at prognostic factors for severe disease, such as seropositivity, elevated inflammatory markers, and erosions. Eberhard and colleagues looked at the relationship between damage as seen on radiography (including erosions and joint space narrowing) and pain and disability in early RA using an inception cohort with <12 months of symptoms. Over 200 patients in Sweden were followed for 5 years with clinical, laboratory, and radiographic evaluations. Of interest, pain was associated with female sex, tender joint count, and inflammatory markers at various time points but not with radiographic damage. This may reflect that pain is related to current inflammation rather than past joint damage or that pain is related to other factors, such as central sensitization. Radiographic damage was, however, associated with disability and thus remains an important target and outcome measure for assessing treatment effectiveness.

Leon and colleagues also looked at early RA but instead, at the category of difficult-to-treat RA (D2T RA), meaning persistent RA symptoms after a trial of at least two biologic or targeted synthetic disease-modifying antirheumatic drugs. In order to gain better insight in preventing D2T RA, the authors examined its association with potentially modifiable risk factors early in the course of disease. Of the over 600 patients followed in this inception cohort, only about 6% were classified as having D2T RA. The study found that patients who had D2T RA tended to be younger, with a higher tender joint count, higher pain scores, and a higher initial level of disability. The Disease Activity Score (DAS28) itself was higher in patients with D2T RA, but the difference did not reach statistical significance. The small number of patients (35) in the D2T RA group may have affected the findings as well as their wider applicability. However, it is interesting to consider whether the associations may also reflect the impact of noninflammatory factors, as in the previous study, on the classification of D2T RA.

Park and colleagues evaluated the difference in clinical outcomes in postmenopausal patients with RA who underwent menopause at younger than 45 years or 45 years or older. Among over 2800 patients in Korea, those who underwent early menopause were more likely to be seronegative and have high disease activity and worse patient-reported outcome scores in fatigue, sleep, and health-related quality of life despite comparable treatments and prevalence of erosions. The authors suggest this may be related to lower cumulative estrogen exposure; whether this correlates to inflammatory cytokine signatures is not yet known. However, as with the prior studies, central sensitization and noninflammatory pain may also contribute and should be considered in interpreting response to therapy.

Finally, addressing the potential risk for cancer in patients with RA before or during treatment with immunosuppressive medications, Miyata and colleagues reported a study that screened nearly 2200 patients who underwent CT (from neck to pelvis) and compared them with those who underwent routine screening with physical exam plus radiography. The study found that CT screening enhanced cancer detection, with a large number of cancers detected at an earlier stage with CT screening compared with routine screening. The overall number of cancers detected was low (33), and thus routine screening with neck-to-pelvis CT for all patients with RA may not be a cost-effective practice. However, it bears further examination for potentially higher-risk populations or specific cancers.

In evaluating the importance of early aggressive treatment of rheumatoid arthritis (RA), we often look at prognostic factors for severe disease, such as seropositivity, elevated inflammatory markers, and erosions. Eberhard and colleagues looked at the relationship between damage as seen on radiography (including erosions and joint space narrowing) and pain and disability in early RA using an inception cohort with <12 months of symptoms. Over 200 patients in Sweden were followed for 5 years with clinical, laboratory, and radiographic evaluations. Of interest, pain was associated with female sex, tender joint count, and inflammatory markers at various time points but not with radiographic damage. This may reflect that pain is related to current inflammation rather than past joint damage or that pain is related to other factors, such as central sensitization. Radiographic damage was, however, associated with disability and thus remains an important target and outcome measure for assessing treatment effectiveness.

Leon and colleagues also looked at early RA but instead, at the category of difficult-to-treat RA (D2T RA), meaning persistent RA symptoms after a trial of at least two biologic or targeted synthetic disease-modifying antirheumatic drugs. In order to gain better insight in preventing D2T RA, the authors examined its association with potentially modifiable risk factors early in the course of disease. Of the over 600 patients followed in this inception cohort, only about 6% were classified as having D2T RA. The study found that patients who had D2T RA tended to be younger, with a higher tender joint count, higher pain scores, and a higher initial level of disability. The Disease Activity Score (DAS28) itself was higher in patients with D2T RA, but the difference did not reach statistical significance. The small number of patients (35) in the D2T RA group may have affected the findings as well as their wider applicability. However, it is interesting to consider whether the associations may also reflect the impact of noninflammatory factors, as in the previous study, on the classification of D2T RA.

Park and colleagues evaluated the difference in clinical outcomes in postmenopausal patients with RA who underwent menopause at younger than 45 years or 45 years or older. Among over 2800 patients in Korea, those who underwent early menopause were more likely to be seronegative and have high disease activity and worse patient-reported outcome scores in fatigue, sleep, and health-related quality of life despite comparable treatments and prevalence of erosions. The authors suggest this may be related to lower cumulative estrogen exposure; whether this correlates to inflammatory cytokine signatures is not yet known. However, as with the prior studies, central sensitization and noninflammatory pain may also contribute and should be considered in interpreting response to therapy.

Finally, addressing the potential risk for cancer in patients with RA before or during treatment with immunosuppressive medications, Miyata and colleagues reported a study that screened nearly 2200 patients who underwent CT (from neck to pelvis) and compared them with those who underwent routine screening with physical exam plus radiography. The study found that CT screening enhanced cancer detection, with a large number of cancers detected at an earlier stage with CT screening compared with routine screening. The overall number of cancers detected was low (33), and thus routine screening with neck-to-pelvis CT for all patients with RA may not be a cost-effective practice. However, it bears further examination for potentially higher-risk populations or specific cancers.