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CHICAGO – while remaining in at least low disease activity in a multicenter, randomized trial with 259 patients.
The results also showed that rheumatoid arthritis (RA) patients randomized to maintain prednisone treatment at 5 mg/day along with tocilizumab fared even better. After 24 weeks of the glucocorticoid-tapering regimen, by which time patients in the tapered arm had their prednisone dosage down to 0 mg, the average change from baseline in their disease activity score 28 with erythrocyte sedimentation rate (DAS28-ESR) was an increase of 0.538, compared with an average drop of 0.075 among untapered patients, a statistically significant difference for the study’s primary endpoint, Gerd R. Burmester, MD, said at the annual meeting of the American College of Rheumatology.
But while the results definitively showed that RA patients treated with the anti-interleukin 6 agent tocilizumab (Actemra) as their primary drug benefited from continued, additional treatment with low-dose prednisone, the results also showed that many patients could come off prednisone without immediate downside. Among the 131 randomized to a forced taper and eventual prednisone discontinuation, 85 (65%) went through this process without flaring and maintained at least low disease activity and sometimes remission, said Dr. Burmester, a professor and director of rheumatology and clinical immunology at Charité Hospital in Berlin. In contrast, 99 of 128 patients (77%) maintained on tocilizumab plus 5 mg/day of prednisone were free from any flares and had at least low disease activity after 24 weeks, a statistically significant between-group difference.
These findings “have potential to inform clinical practice and aid in conversations with patients. RA patients who achieve at least low disease activity while receiving tocilizumab and long-term glucocorticoid treatment at 5 mg/day should be considered for tapering of their glucocorticoid dosage, ideally targeting discontinuation,” Dr. Burmester said.
Addressing a comment from the audience that it’s common knowledge that patients who are well controlled on a potent immunomodulating drug like tocilizumab can often successfully wean off a glucocorticoid, Dr. Burmester insisted that it was important to show this in a randomized, blinded trial.
“When they discontinue [a glucocorticoid] patients can develop myalgias or other symptoms and we haven’t known whether that was real or psychological. In this study patients did not know whether they were being discontinued, so the psychological element was gone,” he said. The new findings confirm in a rigorous way that “we could discontinue a substantial number of patients who probably no longer need a glucocorticoid. It’s an important discussion” for clinicians to have with patients.
The SEMIRA (Steroid Elimination in RA) trial enrolled 68 patients who had already begun tocilizumab treatment and 191 patients new to the drug who had a 24-week run-in on tocilizumab, all of whom also received 5 mg prednisone daily. The trial included 46 sites in five European countries plus Russia and Tunisia. During the main 24-week phase of the study, 128 patients remained on their entry regimen of tocilizumab and prednisone, with 112 completers; 131 others went through a forced taper that culminated in no prednisone administered during the final 8 weeks, with 114 completers. Patients averaged about 54 years old, and just over three-quarters were women. Almost two-thirds of patients also received a nonbiologic disease-modifying antirheumatic drug.
A time-trend analysis of changes in DAS28-ERS showed that, while the difference in change from baseline in disease activity between the two treatment arms separated early in the taper process, the biggest uptick in DAS28-ESR in the patients coming off prednisone occurred once the final 1 mg/day dose was stopped.
The results also showed that tapering led to a statistically significant rise in the clinical disease activity index for RA, compared with that seen with not tapering, and tapering also was linked significantly with an increase in serum markers of bone turnover. The safety analysis showed no striking between-group differences in adverse events and in serious adverse events, and no patients developed confirmed adrenal insufficiency that required replacement therapy.
SOURCE: Burmester G et al. Arthritis Rheumatol. 2018;70(suppl 10): Abstract L18.
Tapering well-controlled rheumatoid arthritis patients off glucocorticoid treatment is often attempted in clinical practice, but until now no evidence base existed to justify this approach. While the results reported by Dr. Burmester from the SEMIRA study are not unexpected, it’s very helpful to see these data from a well-designed study.
What remains unclear is the generalizability of the findings: Do they only apply to patients receiving tocilizumab as their primary antirheumatic drug or does glucocorticoid tapering work the same way in RA patients on different drugs?
The results also confirm another impression that many clinicians have had but until now was unsubstantiated: Eliminating the final 1 mg of daily glucocorticoid treatment is the most difficult part of tapering patients down to complete corticosteroid withdrawal. What often happens in practice is that patients get down to the last 1 or 2 mg of daily glucocorticoid treatment but further reduction beyond that causes a flare or a manifestation of steroid-withdrawal syndrome.
The results from this study give clinicians a better context for discussing glucocorticoid tapering with patients. Even with a potent antirheumatic drug like tocilizumab, it’s hard for some patients to completely withdraw from a glucocorticoid. Even at very low dosages glucocorticoids still have a very meaningful effect on some patients.
David S. Pisetsky, MD , is a professor of medicine at Duke University in Durham, N.C. He has been a consultant to Celgene, Celltrion, GlaxoSmithKline, and Lilly, and he has received research support from Pfizer. He made these comments in an interview.
Tapering well-controlled rheumatoid arthritis patients off glucocorticoid treatment is often attempted in clinical practice, but until now no evidence base existed to justify this approach. While the results reported by Dr. Burmester from the SEMIRA study are not unexpected, it’s very helpful to see these data from a well-designed study.
What remains unclear is the generalizability of the findings: Do they only apply to patients receiving tocilizumab as their primary antirheumatic drug or does glucocorticoid tapering work the same way in RA patients on different drugs?
The results also confirm another impression that many clinicians have had but until now was unsubstantiated: Eliminating the final 1 mg of daily glucocorticoid treatment is the most difficult part of tapering patients down to complete corticosteroid withdrawal. What often happens in practice is that patients get down to the last 1 or 2 mg of daily glucocorticoid treatment but further reduction beyond that causes a flare or a manifestation of steroid-withdrawal syndrome.
The results from this study give clinicians a better context for discussing glucocorticoid tapering with patients. Even with a potent antirheumatic drug like tocilizumab, it’s hard for some patients to completely withdraw from a glucocorticoid. Even at very low dosages glucocorticoids still have a very meaningful effect on some patients.
David S. Pisetsky, MD , is a professor of medicine at Duke University in Durham, N.C. He has been a consultant to Celgene, Celltrion, GlaxoSmithKline, and Lilly, and he has received research support from Pfizer. He made these comments in an interview.
Tapering well-controlled rheumatoid arthritis patients off glucocorticoid treatment is often attempted in clinical practice, but until now no evidence base existed to justify this approach. While the results reported by Dr. Burmester from the SEMIRA study are not unexpected, it’s very helpful to see these data from a well-designed study.
What remains unclear is the generalizability of the findings: Do they only apply to patients receiving tocilizumab as their primary antirheumatic drug or does glucocorticoid tapering work the same way in RA patients on different drugs?
The results also confirm another impression that many clinicians have had but until now was unsubstantiated: Eliminating the final 1 mg of daily glucocorticoid treatment is the most difficult part of tapering patients down to complete corticosteroid withdrawal. What often happens in practice is that patients get down to the last 1 or 2 mg of daily glucocorticoid treatment but further reduction beyond that causes a flare or a manifestation of steroid-withdrawal syndrome.
The results from this study give clinicians a better context for discussing glucocorticoid tapering with patients. Even with a potent antirheumatic drug like tocilizumab, it’s hard for some patients to completely withdraw from a glucocorticoid. Even at very low dosages glucocorticoids still have a very meaningful effect on some patients.
David S. Pisetsky, MD , is a professor of medicine at Duke University in Durham, N.C. He has been a consultant to Celgene, Celltrion, GlaxoSmithKline, and Lilly, and he has received research support from Pfizer. He made these comments in an interview.
CHICAGO – while remaining in at least low disease activity in a multicenter, randomized trial with 259 patients.
The results also showed that rheumatoid arthritis (RA) patients randomized to maintain prednisone treatment at 5 mg/day along with tocilizumab fared even better. After 24 weeks of the glucocorticoid-tapering regimen, by which time patients in the tapered arm had their prednisone dosage down to 0 mg, the average change from baseline in their disease activity score 28 with erythrocyte sedimentation rate (DAS28-ESR) was an increase of 0.538, compared with an average drop of 0.075 among untapered patients, a statistically significant difference for the study’s primary endpoint, Gerd R. Burmester, MD, said at the annual meeting of the American College of Rheumatology.
But while the results definitively showed that RA patients treated with the anti-interleukin 6 agent tocilizumab (Actemra) as their primary drug benefited from continued, additional treatment with low-dose prednisone, the results also showed that many patients could come off prednisone without immediate downside. Among the 131 randomized to a forced taper and eventual prednisone discontinuation, 85 (65%) went through this process without flaring and maintained at least low disease activity and sometimes remission, said Dr. Burmester, a professor and director of rheumatology and clinical immunology at Charité Hospital in Berlin. In contrast, 99 of 128 patients (77%) maintained on tocilizumab plus 5 mg/day of prednisone were free from any flares and had at least low disease activity after 24 weeks, a statistically significant between-group difference.
These findings “have potential to inform clinical practice and aid in conversations with patients. RA patients who achieve at least low disease activity while receiving tocilizumab and long-term glucocorticoid treatment at 5 mg/day should be considered for tapering of their glucocorticoid dosage, ideally targeting discontinuation,” Dr. Burmester said.
Addressing a comment from the audience that it’s common knowledge that patients who are well controlled on a potent immunomodulating drug like tocilizumab can often successfully wean off a glucocorticoid, Dr. Burmester insisted that it was important to show this in a randomized, blinded trial.
“When they discontinue [a glucocorticoid] patients can develop myalgias or other symptoms and we haven’t known whether that was real or psychological. In this study patients did not know whether they were being discontinued, so the psychological element was gone,” he said. The new findings confirm in a rigorous way that “we could discontinue a substantial number of patients who probably no longer need a glucocorticoid. It’s an important discussion” for clinicians to have with patients.
The SEMIRA (Steroid Elimination in RA) trial enrolled 68 patients who had already begun tocilizumab treatment and 191 patients new to the drug who had a 24-week run-in on tocilizumab, all of whom also received 5 mg prednisone daily. The trial included 46 sites in five European countries plus Russia and Tunisia. During the main 24-week phase of the study, 128 patients remained on their entry regimen of tocilizumab and prednisone, with 112 completers; 131 others went through a forced taper that culminated in no prednisone administered during the final 8 weeks, with 114 completers. Patients averaged about 54 years old, and just over three-quarters were women. Almost two-thirds of patients also received a nonbiologic disease-modifying antirheumatic drug.
A time-trend analysis of changes in DAS28-ERS showed that, while the difference in change from baseline in disease activity between the two treatment arms separated early in the taper process, the biggest uptick in DAS28-ESR in the patients coming off prednisone occurred once the final 1 mg/day dose was stopped.
The results also showed that tapering led to a statistically significant rise in the clinical disease activity index for RA, compared with that seen with not tapering, and tapering also was linked significantly with an increase in serum markers of bone turnover. The safety analysis showed no striking between-group differences in adverse events and in serious adverse events, and no patients developed confirmed adrenal insufficiency that required replacement therapy.
SOURCE: Burmester G et al. Arthritis Rheumatol. 2018;70(suppl 10): Abstract L18.
CHICAGO – while remaining in at least low disease activity in a multicenter, randomized trial with 259 patients.
The results also showed that rheumatoid arthritis (RA) patients randomized to maintain prednisone treatment at 5 mg/day along with tocilizumab fared even better. After 24 weeks of the glucocorticoid-tapering regimen, by which time patients in the tapered arm had their prednisone dosage down to 0 mg, the average change from baseline in their disease activity score 28 with erythrocyte sedimentation rate (DAS28-ESR) was an increase of 0.538, compared with an average drop of 0.075 among untapered patients, a statistically significant difference for the study’s primary endpoint, Gerd R. Burmester, MD, said at the annual meeting of the American College of Rheumatology.
But while the results definitively showed that RA patients treated with the anti-interleukin 6 agent tocilizumab (Actemra) as their primary drug benefited from continued, additional treatment with low-dose prednisone, the results also showed that many patients could come off prednisone without immediate downside. Among the 131 randomized to a forced taper and eventual prednisone discontinuation, 85 (65%) went through this process without flaring and maintained at least low disease activity and sometimes remission, said Dr. Burmester, a professor and director of rheumatology and clinical immunology at Charité Hospital in Berlin. In contrast, 99 of 128 patients (77%) maintained on tocilizumab plus 5 mg/day of prednisone were free from any flares and had at least low disease activity after 24 weeks, a statistically significant between-group difference.
These findings “have potential to inform clinical practice and aid in conversations with patients. RA patients who achieve at least low disease activity while receiving tocilizumab and long-term glucocorticoid treatment at 5 mg/day should be considered for tapering of their glucocorticoid dosage, ideally targeting discontinuation,” Dr. Burmester said.
Addressing a comment from the audience that it’s common knowledge that patients who are well controlled on a potent immunomodulating drug like tocilizumab can often successfully wean off a glucocorticoid, Dr. Burmester insisted that it was important to show this in a randomized, blinded trial.
“When they discontinue [a glucocorticoid] patients can develop myalgias or other symptoms and we haven’t known whether that was real or psychological. In this study patients did not know whether they were being discontinued, so the psychological element was gone,” he said. The new findings confirm in a rigorous way that “we could discontinue a substantial number of patients who probably no longer need a glucocorticoid. It’s an important discussion” for clinicians to have with patients.
The SEMIRA (Steroid Elimination in RA) trial enrolled 68 patients who had already begun tocilizumab treatment and 191 patients new to the drug who had a 24-week run-in on tocilizumab, all of whom also received 5 mg prednisone daily. The trial included 46 sites in five European countries plus Russia and Tunisia. During the main 24-week phase of the study, 128 patients remained on their entry regimen of tocilizumab and prednisone, with 112 completers; 131 others went through a forced taper that culminated in no prednisone administered during the final 8 weeks, with 114 completers. Patients averaged about 54 years old, and just over three-quarters were women. Almost two-thirds of patients also received a nonbiologic disease-modifying antirheumatic drug.
A time-trend analysis of changes in DAS28-ERS showed that, while the difference in change from baseline in disease activity between the two treatment arms separated early in the taper process, the biggest uptick in DAS28-ESR in the patients coming off prednisone occurred once the final 1 mg/day dose was stopped.
The results also showed that tapering led to a statistically significant rise in the clinical disease activity index for RA, compared with that seen with not tapering, and tapering also was linked significantly with an increase in serum markers of bone turnover. The safety analysis showed no striking between-group differences in adverse events and in serious adverse events, and no patients developed confirmed adrenal insufficiency that required replacement therapy.
SOURCE: Burmester G et al. Arthritis Rheumatol. 2018;70(suppl 10): Abstract L18.
REPORTING FROM THE ACR ANNUAL MEETING
Key clinical point: Many rheumatoid arthritis patients with low disease activity on tocilizumab plus a glucocorticoid can taper off the corticosteroid without flaring.
Major finding: In RA patients with low disease activity on tocilizumab plus prednisone, 65% came off the glucocorticoid without flaring or relapse.
Study details: SEMIRA, a multicenter, randomized study with 259 rheumatoid arthritis patients.
Disclosures: SEMIRA was funded by Hoffmann-La Roche. Dr. Burmester has been a consultant to and speaker on behalf of Roche and Sanofi-Genzyme.
Source: Burmester G et al. Arthritis Rheumatol. 2018;70(suppl 10): Abstract L18.