In This Article
- Guidelines for Switching Between Biologic Therapies in Patients with PsA
- Golimumab Effective for RA After Inadequate Response to Tocilizumab
- Biomarkers of Disease Activity Should Be Interpreted Carefully in Obese Women with RA
Guidelines for Switching Between Biologic Therapies in Patients with PsA
Psoriatic arthritis (PsA) is characterized by joint stiffness, swelling, and tenderness, and affects approximately 25% of patients with psoriasis. Biologic disease-modifying antirheumatic drugs (DMARDs), recommended for patients who do not respond to nonbiologic DMARDs, have revolutionized the treatment armamentarium for PsA, and include tumor necrosis factor (TNF) inhibitors and non-TNF inhibitors. Although research suggests that patients who do not respond to one biologic DMARD should switch to another biologic DMARD, there are limited data to help guide clinicians in the choice of these agents. This led researchers to review the published literature and consensus guidelines and develop guidance on switching between biologic DMARDs in patients with PsA (Merola JF, et al. Semin Arthritis Rheum. 2017 Feb 8. Epub ahead of print).
The researchers recognized that PsA is a heterogeneous disease, and therefore, there are no algorithms to follow when altering patients’ treatment regimens. However, they recommended not switching biologic therapy within the first 3 months of starting therapy, except when there are serious safety concerns or there is no response to initial therapy.
The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis recommends that patients with PsA who do not respond to biologic therapy should switch to an alternative biologic, either within a drug class or with a different mechanism of action. In addition, expert consensus from the Delphi survey revealed that patients who do not respond to a first-line biologic DMARD should switch to a biologic DMARD with a different mechanism of action. However, the researchers recommended first increasing the dose of a biologic within the class, or adding methotrexate to the biologic, before switching to a biologic with a different mechanism of action.
The researchers emphasized that biologic DMARDs have different dosing regimens, routes of administration, and mechanisms of action, all of which should be taken into consideration when selecting biologic therapies. In addition, because TNF inhibitors may worsen symptoms of PsA, switching to a drug with a similar mechanism of action is not recommended.
Furthermore, the safety of different biologic DMARDs should also be considered, especially in patients with cardiovascular disease and in women of childbearing age. For example, TNF inhibitors are not recommended in patients with advanced congestive heart failure, systemic lupus erythematosus, demyelinating diseases, and other autoimmune diseases. In addition, the management of patients with PsA and cardiovascular diseases should involve a team approach, including cardiologists, dermatologists, rheumatologists, and primary care physicians.
Patient and physician preferences should be an important part of treatment decision-making. Some patients prefer self-administering biologic drugs via subcutaneous injection, whereas others prefer infusions administered by healthcare professionals. Physician barriers to prescribing biologic DMARDs include costs, safety concerns, administrative burdens, and educating patients about self-injections and risk factors.
Biologic DMARDs with different mechanisms of action are in clinical development, including interleukin (IL)-17 inhibitors, IL-23 inhibitors, oral Janus kinase inhibitors, and IL-6 inhibitors. The researchers stated that these emerging agents “may establish themselves as viable, and in some cases superior, alternatives” to TNF inhibitors for the management of patients with PsA.
Golimumab Effective for RA After Inadequate Response to Tocilizumab
Biologic disease-modifying antirheumatic drugs, including tumor necrosis factor (TNF) inhibitors and non-TNF inhibitors, have been the cornerstone of therapy for rheumatoid arthritis (RA) for more than 10 years. Although switching from a first-line TNF inhibitor to a second-line non-TNF inhibitor was shown to be more effective than switching to another TNF inhibitor, the use of the non-TNF inhibitor tocilizumab as first-line therapy, followed by a TNF inhibitor as second-line therapy, has not been assessed in clinical trials. Therefore, investigators examined the efficacy of the TNF inhibitor golimumab as second-line therapy after inadequate response to the non-TNF inhibitor tocilizumab in patients with RA (Matsuno H, Katayama K. Mod Rheumatol. 2017;27:246-251).
Overall, 26 patients with an inadequate response to first-line therapy tocilizumab were compared with 19 patients who had an inadequate response to a TNF inhibitor after 24 weeks of treatment. Both patient groups received golimumab as second-line therapy, and the Disease Activity Score based on 28 joints erythrocyte sedimentation rate (DAS28-ESR) were reviewed at baseline, 24 weeks after starting first-line therapy, and at 52 weeks after starting golimumab therapy.
Both groups of patients achieved a significant improvement in DAS28-ESR scores from baseline. In addition, 42% of patients who received first-line tocilizumab, followed by golimumab, achieved remission (DAS28 ≤2.6) compared with approximately 20% of patients who received a first-line TNF inhibitor, followed by golimumab.
The probability of treatment retention at week 52 was significantly higher in patients who received first-line tocilizumab, followed by golimumab than in patients who received a TNF inhibitor, followed by golimumab (81% vs 68%, respectively; P = .03).
Furthermore, the proportion of patients with no response was significantly lower at 52 weeks than at 24 weeks in both groups, although there was no significant difference between the groups.
Overall, these robust efficacy results obtained from switching from a non-TNF inhibitor to a TNF inhibitor with a different mechanism of action echo those of previous clinical trials that used a TNF inhibitor as first-line therapy and a non-TNF inhibitor as second-line therapy.
Biomarkers of Disease Activity Should Be Interpreted Carefully in Obese Women with RA
The inflammatory biomarkers C-reactive protein (CRP) and eythrocyte sedimentation rate (ESR) are often used to assess disease activity and guide treatment decisions in patients with rheumatoid arthritis (RA). Data show that obese individuals, especially obese women, have higher CRP levels than the general population, but increased CRP levels in these individuals may not necessarily be indicative of high disease activity. Therefore, always attributing elevated CRP levels in obese patients to RA disease activity may result in the inaccurate assessment of disease activity. Because published data regarding this subject are sparse, especially in severely obese individuals, researchers sought to evaluate the association between body mass index (BMI) and inflammatory markers in RA, whether these associations are comparable in patients without RA, and the impact of obesity on disease activity measures (George MD, et al. Arthritis Care Res [Hoboken]. 2017 Apr 10. Epub ahead of print).
The investigators pooled data from 3 studies (N = 451) and the Veterans Affairs Rheumatoid Arthritis Registry (N = 1652) to assess the association between BMI and CRP and ESR in obese patients with RA compared with the general population that did not have RA, using the National Health and Nutrition Examination Survey.
Severely obese women with RA had higher CRP levels than women with a normal BMI, independent of other disease activity components, such as greater swollen joint count, tender joint count, or patient global scores. Association between abnormal BMI and increased CRP levels was also observed in the general population that did not have RA, suggesting that higher CRP levels in obese women with RA may be attributed to adiposity rather than to increased disease activity. This finding is not unusual, given that adipose tissue produces interleukin-6 and other inflammatory cytokines, which can elevate CRP levels in obese individuals. Positive relationships between BMI and ESR in women were more modest than associations between BMI and CRP levels.
The association between high BMI scores and CRP levels was not observed in men with RA. Conversely, underweight men with RA had high CRP and ESR levels; given that both men and women without RA demonstrated an association between high BMI levels and increased CRP levels, the researchers attributed this unusual finding in men to RA-related factors, such as increased inflammation or comorbid conditions, and not to adiposity.
In approximately 10% of severely obese women, the correction of CRP values resulted in reclassification of RA disease activity, indicating that obesity may affect the performance of CRP as a biomarker of disease activity, and should be interpreted cautiously, the investigators concluded.