A treatment regimen that maximizes the use of hydroxychloroquine, pulse methyl-prednisolone, and methotrexate — while reducing doses of oral prednisone — leads to better outcomes, including prolonged clinical remission, among people with systemic lupus erythematosus (SLE), a study suggests.
The study, “Prolonged remission in SLE is possible by using reduced doses of prednisone: An observational study from the Lupus-Cruces and Lupus-Bordeaux inception cohorts,” was published in the journal Autoimmunity Reviews.
Clinical remission is an important treatment goal for people with SLE. As such, it is frequently used as a primary endpoint for clinical trials.
However, in the past, researchers had used different definitions for the term remission, making it difficult to compare results across studies. So, an international task force — DORIS – Definition of Remission in SLE — met in 2015, and came to a consensus on a single definition of remission in SLE.
The committee grouped SLE remission into categories: complete remission (ComR), clinical remission (ClinR), complete remission on treatment (ComROnT), and clinical remission on treatment (ClinROnT).
In clinical terms, ClinROnT is defined as having an SLE Disease Activity Index (SLEDAI) — a validated measure of disease activity in SLE — score of zero and a physician global assessment below 0.5. Treatment with hydroxychloroquine, immunosuppressive medicines, and prenisolone was allowed in these patients as long as doses were no higher than 5 mg per day.
“Of note, as ClinROnT is the less stringent type of remission, all patients fulfilling criteria for the other three types of remission were also classified as being in ClinROnT,” the researchers said.
Now, researchers set out to compare the rates of remission — according to the DORIS definition — of people with SLE from two well-characterized European groups. The investigators examined the remission rates of the Spanish Cruces University Hospital Cohort, and the French Bordeaux University Hospital Cohort, over a period of five years.
The therapeutic approach between the two groups was different. Those in the Spanish group received more frequent pulses of methyl-prednisolone (an immunosuppressant), hydroxychloroquine (an anti-malarial), and methotrexate (an immunosuppressant). This allowed them to reduce the amount of oral prednisone that they received.
Prednisone is an immunosuppressant that is frequently prescribed for people with SLE. However, long-term use of prednisone is associated with significant side effects. Thus, there is a need for better treatment regimens.
The main endpoint of this study was the achievement of clinical remission on treatment (ClinROnT). This parameter was assessed every year, from the first until the fifth year following the SLE diagnosis.
In total, researchers studied 173 patients, including 92 in the Spanish group and 81 in the French. The clinical presentation of both groups was similar, with no significant differences in disease severity as determined by SLEDAI scores.
During the study period, patients in the Spanish group were treated more frequently with hydroxychloroquine (97% vs. 80% in the first year), and for longer periods (57 months vs. 43 months), as compared with the French group. Those in Spain also received more frequent methotrexate (24% vs. 11%) and pulse methyl-prednisolone (42% vs. 26%) during the course of the study.
Most likely as a consequence of receiving other treatment options, the doses of prednisolone given to the Spanish group were significantly lower than those given to the French group, irrespective of their disease activity scores at enrollment.
Interestingly, researchers found that more people in the Spanish group achieved ClinROnT at any timepoint, although differences were more marked in the first year — at 84% vs. 43% in the French group.
Prolonged ClinROnT — achieving remission criteria during the five consecutive yearly visits — also was more frequent in the Spanish (70%) than in the French group (28%).
Finally, researchers found that people in the Spanish group were 69% more likely to achieve ClinROnT than those in the French group, after adjusting for initial SLEDAI scores. That number increased to 72% more likely after controlling for the presenting clinical manifestations.
Overall, a higher baseline SLEDAI score and neurological symptoms were the only two factors that significantly lowered the chances of achieving ClinROnT.
Thus, the investigators concluded that “prolonged ClinROnT was achievable by using a therapeutic regime consisting of lower doses of oral prednisone and maximizing the use of hydroxychloroquine, pulse methyl-prednisolone and methotrexate.”