CRP predicts anti-TNF response in ankylosing spondylitis

Patients with ankylosing spondylitis whose baseline C-reactive protein (CRP) levels were more than three times the upper limit of normal were significantly more likely to respond to 12 weeks of etanercept therapy than were patients with normal baseline CRP levels, investigators reported.

In a post hoc study of 867 patients who received etanercept during clinical trials, the adjusted odds of achieving 20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) at week 12 were 190% higher when CRP levels were “very high” rather than normal at baseline (odds ratio, 2.9; 95% confidence interval, 1.8-4.7). Very-high baseline CRP levels (more than three times the upper limit of normal) also significantly predicted week-12 ASAS50, a change in Ankylosing Spondylitis Disease Activity Score based on CRP (ASDAS-CRP) greater than 1.1 (clinically important improvement), and an ASDAS-CRP less than 1.3 (inactive disease), while a normalization of very-high CRP levels by 2, 4, or 8 weeks of treatment was a significant predictor of achieving week-12 ASDAS inactive disease. “Patient-reported outcomes were less consistent predictors of response,” Xenofon Baraliakos, MD, of Ruhr University Bochum in Herne, Germany, and his coinvestigators wrote in Seminars in Arthritis and Rheumatism.


While the advent of tumor necrosis factor (TNF) antagonists has greatly improved outcomes in ankylosing spondylitis, symptom ambiguity and a lack of objective response criteria still impede early diagnosis and radiographic interpretation. Elevated baseline CRP predicted clinical response to anti-TNF therapy by patients with ankylosing spondylitis in several prior post hoc studies. To further evaluate this finding, the researchers pooled and analyzed data from four randomized, placebo-controlled trials of etanercept in adults with ankylosing spondylitis. In all, 43% of patients had a normal baseline CRP level, 34% had a level that was elevated but did not exceed three times the upper limit of normal, and 23% had a very-high level.

Age of onset, disease duration, and baseline Bath Ankylosing Spondylitis Functional Index also predicted response to etanercept therapy. After controlling for these covariates, a very-high baseline CRP remained a significant predictor for all four week-12 outcomes. This finding points to the value of aggressive, early treatment to normalize CRP in patients with ankylosing spondylitis, the researchers wrote. “Bending the curve of inflammation in the early disease may alter the long-term trajectory of ankylosing spondylitis, which is an opportunity that may not exist in the later stages.”

Thus, CRP, in addition to patient-reported and clinical outcomes, might be useful to help monitor response to anti-TNF therapy, the investigators wrote. It remains unclear whether elevated CRP levels also predict future treatment response in patients who are currently clinically improved or stable.

Pfizer funded the post hoc analysis and acquired the company that had funded the trials (Wyeth). Dr. Baraliakos reported consultancy and speaker fees from Pfizer, AbbVie, Bristol-Myers Squibb, Celgene, Chugai, Janssen, Merck, Novartis, Sandoz, and UCB. Two coinvestigators were Pfizer employees. A third coinvestigator was contracted by Pfizer to provide statistical support.

SOURCE: Baraliakos X et al. Semin Arthritis Rheum. 2018 Nov 2. doi: 10.1016/j.semarthrit.2018.10.019.

Patients with ankylosing spondylitis whose baseline C-reactive protein (CRP) levels were more than three times the upper limit of normal were significantly more likely to respond to 12 weeks of etanercept therapy than were patients with normal baseline CRP levels, investigators reported.

In a post hoc study of 867 patients who received etanercept during clinical trials, the adjusted odds of achieving 20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) at week 12 were 190% higher when CRP levels were “very high” rather than normal at baseline (odds ratio, 2.9; 95% confidence interval, 1.8-4.7). Very-high baseline CRP levels (more than three times the upper limit of normal) also significantly predicted week-12 ASAS50, a change in Ankylosing Spondylitis Disease Activity Score based on CRP (ASDAS-CRP) greater than 1.1 (clinically important improvement), and an ASDAS-CRP less than 1.3 (inactive disease), while a normalization of very-high CRP levels by 2, 4, or 8 weeks of treatment was a significant predictor of achieving week-12 ASDAS inactive disease. “Patient-reported outcomes were less consistent predictors of response,” Xenofon Baraliakos, MD, of Ruhr University Bochum in Herne, Germany, and his coinvestigators wrote in Seminars in Arthritis and Rheumatism.


While the advent of tumor necrosis factor (TNF) antagonists has greatly improved outcomes in ankylosing spondylitis, symptom ambiguity and a lack of objective response criteria still impede early diagnosis and radiographic interpretation. Elevated baseline CRP predicted clinical response to anti-TNF therapy by patients with ankylosing spondylitis in several prior post hoc studies. To further evaluate this finding, the researchers pooled and analyzed data from four randomized, placebo-controlled trials of etanercept in adults with ankylosing spondylitis. In all, 43% of patients had a normal baseline CRP level, 34% had a level that was elevated but did not exceed three times the upper limit of normal, and 23% had a very-high level.

Age of onset, disease duration, and baseline Bath Ankylosing Spondylitis Functional Index also predicted response to etanercept therapy. After controlling for these covariates, a very-high baseline CRP remained a significant predictor for all four week-12 outcomes. This finding points to the value of aggressive, early treatment to normalize CRP in patients with ankylosing spondylitis, the researchers wrote. “Bending the curve of inflammation in the early disease may alter the long-term trajectory of ankylosing spondylitis, which is an opportunity that may not exist in the later stages.”

Thus, CRP, in addition to patient-reported and clinical outcomes, might be useful to help monitor response to anti-TNF therapy, the investigators wrote. It remains unclear whether elevated CRP levels also predict future treatment response in patients who are currently clinically improved or stable.

Pfizer funded the post hoc analysis and acquired the company that had funded the trials (Wyeth). Dr. Baraliakos reported consultancy and speaker fees from Pfizer, AbbVie, Bristol-Myers Squibb, Celgene, Chugai, Janssen, Merck, Novartis, Sandoz, and UCB. Two coinvestigators were Pfizer employees. A third coinvestigator was contracted by Pfizer to provide statistical support.

SOURCE: Baraliakos X et al. Semin Arthritis Rheum. 2018 Nov 2. doi: 10.1016/j.semarthrit.2018.10.019.

Patients with ankylosing spondylitis whose baseline C-reactive protein (CRP) levels were more than three times the upper limit of normal were significantly more likely to respond to 12 weeks of etanercept therapy than were patients with normal baseline CRP levels, investigators reported.

In a post hoc study of 867 patients who received etanercept during clinical trials, the adjusted odds of achieving 20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) at week 12 were 190% higher when CRP levels were “very high” rather than normal at baseline (odds ratio, 2.9; 95% confidence interval, 1.8-4.7). Very-high baseline CRP levels (more than three times the upper limit of normal) also significantly predicted week-12 ASAS50, a change in Ankylosing Spondylitis Disease Activity Score based on CRP (ASDAS-CRP) greater than 1.1 (clinically important improvement), and an ASDAS-CRP less than 1.3 (inactive disease), while a normalization of very-high CRP levels by 2, 4, or 8 weeks of treatment was a significant predictor of achieving week-12 ASDAS inactive disease. “Patient-reported outcomes were less consistent predictors of response,” Xenofon Baraliakos, MD, of Ruhr University Bochum in Herne, Germany, and his coinvestigators wrote in Seminars in Arthritis and Rheumatism.


While the advent of tumor necrosis factor (TNF) antagonists has greatly improved outcomes in ankylosing spondylitis, symptom ambiguity and a lack of objective response criteria still impede early diagnosis and radiographic interpretation. Elevated baseline CRP predicted clinical response to anti-TNF therapy by patients with ankylosing spondylitis in several prior post hoc studies. To further evaluate this finding, the researchers pooled and analyzed data from four randomized, placebo-controlled trials of etanercept in adults with ankylosing spondylitis. In all, 43% of patients had a normal baseline CRP level, 34% had a level that was elevated but did not exceed three times the upper limit of normal, and 23% had a very-high level.

Age of onset, disease duration, and baseline Bath Ankylosing Spondylitis Functional Index also predicted response to etanercept therapy. After controlling for these covariates, a very-high baseline CRP remained a significant predictor for all four week-12 outcomes. This finding points to the value of aggressive, early treatment to normalize CRP in patients with ankylosing spondylitis, the researchers wrote. “Bending the curve of inflammation in the early disease may alter the long-term trajectory of ankylosing spondylitis, which is an opportunity that may not exist in the later stages.”

Thus, CRP, in addition to patient-reported and clinical outcomes, might be useful to help monitor response to anti-TNF therapy, the investigators wrote. It remains unclear whether elevated CRP levels also predict future treatment response in patients who are currently clinically improved or stable.

Pfizer funded the post hoc analysis and acquired the company that had funded the trials (Wyeth). Dr. Baraliakos reported consultancy and speaker fees from Pfizer, AbbVie, Bristol-Myers Squibb, Celgene, Chugai, Janssen, Merck, Novartis, Sandoz, and UCB. Two coinvestigators were Pfizer employees. A third coinvestigator was contracted by Pfizer to provide statistical support.

SOURCE: Baraliakos X et al. Semin Arthritis Rheum. 2018 Nov 2. doi: 10.1016/j.semarthrit.2018.10.019.